scholarly journals Real World Prospective Observational Multicenter Trial of Venetoclax-Based Therapy for Patients with AML Reveals Unique Patterns of Patient Selection and Treatment Utilization - Revive Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1246-1246
Author(s):  
Ofir Wolach ◽  
Itai Levi ◽  
David Lavie ◽  
Jonathan Canaani ◽  
Sigal Tavor ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Patient Selection ◽  
Real World ◽  
Research Funding ◽  
Early Death ◽  
Treatment Patterns ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Related Factors

Abstract Background: Venetoclax-based combinations were recently approved to treat patients (pts) with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Limited prospective 'real-world' data is available on treatment patterns of venetoclax-based therapy in routine clinical practice. We investigated patterns of patient selection, efficacy, toxicity, patient related outcome and post-remission management in a nationwide multicenter prospective observational trial. Methods: Newly diagnosed pts with AML were enrolled at the time of venetoclax-based therapy initiation from 10 medical centers in Israel. Demographic, clinical and patient-related baseline characteristics were documented. Treatment patterns, safety and efficacy outcomes are reported. Results: Between August 12, 2019, and June 17, 2021(data cut) ,127 AML pts were enrolled to receive venetoclax based therapy. Baseline patient and disease characteristics are reported in Table 1. The main reasons for physician's choice of venetoclax-based therapy were age ≥75, comorbidities and ECOG ≥2 (patient related factors) in 76% of cases and adverse disease biology predicting poor response to intensive chemotherapy (disease related factors) in 24% of cases. Most pts started therapy in an inpatient setting, 82 (64.6%) with a median hospitalization duration of 14 days, while 44 pts (34.6%) started therapy as out pts. Pts received a median of 3.8 cycles of therapy (range 1-21). Most pts (97%) received venetoclax in combination with hypomethylating agents. The full dose of 400mg QD after a median ramp-up duration of 3 days was achieved in 88% of the pts. Dose interruptions and dose modifications during follow-up occurred in 59 (46%) and 30 (24%) of pts, respectively. To allow for adequate follow up for response assessment, efficacy analysis was limited to pts enrolled prior to December 31, 2020, and included 108 pts with a median follow-up of 8 months (range 1-20). As of data cut, 93 pts completed cycle 1 of therapy, 66 pts completed cycle 3 and 39 pts completed cycle 6. 29 pts (27%) are still active on treatment. Best composite complete remission [CCR = complete remission (CR) plus CR with incomplete count recovery (CRi)] was achieved in 62 (57%) pts. CCR rates were assessed in different pre-defined subgroups. Best CCR in pts selected for therapy based on disease-related and patient-related factors were 70% and 54% respectively. Best CCR in pts with AML arising from MPN and pts with other AML were 45% and 58% respectively. Estimated median overall survival (OS) of all pts was 9.6 months (range 7.4-10.6) (Figure 1). Achieving CCR was associated with a superior probability for survival. Estimated median OS was 13.6 months (range 10.6 - not reached) in pts achieving CCR and 4.2 months (range 1.2-10.3) in non-CCR (p<.0001). Of responding pts (CR/CRi, partial remission (PR), morphologic leukemia free state (MLFS), 27 (37%) progressed. Estimated median time to progression was 9.2 months (6.7-NR). Allogeneic transplantation following venetoclax based treatment was offered to 16 (26%) pts with a median age of 71 years (range 43-77). Last documented response prior to transplant was CR in 5 (32%) pts, CRi 9 (56%), MLFS 1 (6%) and PR in 1 (6%) patient. Among grade ≥3 AEs were febrile neutropenia in 28% and infections in 21% of pts. Clinical and laboratory tumor lysis syndrome (TLS) was documented in 2 and 4 pts, respectively. Antifungal prophylaxis was administered in 20% of pts and granulocyte colony-stimulating factor (GCSF) support was used in 17% of pts in response. Early death rate at 30 and 60 days were 7% and 13%, respectively. Conclusion: This prospective real-world analysis reveals unique patterns of patient selection and venetoclax treatment utilization in a medical system with wide access for this indication. Venetoclax-based therapies are effective and associated with manageable toxicity, including in AML patient populations that were excluded from previous registration trials with comparable CCR and early death rates. Factors associated with patient selection in the 'real-world' setting and immature follow up data most probably led to a shorter estimated median OS in this analysis as compared to controlled trials. The REVIVE study continues to expand and is expected to provide additional insights on treatment patterns, management as well as clinical and patient related outcomes. Figure 1 Figure 1. Disclosures Wolach: Janssen: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Astellas: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; Neopharm: Consultancy. Levi: AbbVie: Consultancy, Research Funding. Lavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures. Tavor: AbbVie: Consultancy. Hellmann: AbbVie: Consultancy. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Zuckerman: Gilead Sciences: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria; Cellect Biotechnology: Honoraria; BioSight Ltd: Honoraria; AbbVie: Honoraria; Orgenesis Inc.: Honoraria. Stemer: AbbVie: Consultancy. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Ofran: Medison Israel: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Moshe: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures.

scholarly journals Real-World Effectiveness of Voxelotor for Treating Sickle Cell Disease in the US

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-25
Author(s):  
Ahmar Urooj Zaidi ◽  
Thokozeni Lipato ◽  
Ofelia A. Alvarez ◽  
Alexander Lonshteyn ◽  
Derek Weycker ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Index Date ◽  
Health Claims ◽  
Transfusion Rate ◽  
Publicly Traded ◽  
Advisory Committees ◽  
The Us

Background: Until late 2019, few treatments had been approved by the FDA for treating sickle cell disease (SCD). Voxelotor (Oxbryta®) is a sickle hemoglobin-polymerization inhibitor approved by the FDA in November 2019 for treatment of SCD in adults and adolescents aged ≥12 years under an accelerated approval based on results of the pivotal HOPE study. In HOPE, voxelotor increased average hemoglobin (Hb) by 1.1 g/dL from baseline in patients with 1-10 vaso-occlusive crises (VOCs) in the previous year and a Hb level between 5.5 and 10.5 g/dL who were not transfusion dependent. Of the participants on voxelotor 1500 mg, 51% had a Hb response >1.0 g/dL at week 24 (Vichinsky et al, NEJM 2019). This study sought to assess the real-world effectiveness of voxelotor based on data during the first 6 months post FDA approval. Methods: Data on medical and pharmacy claims for patients who were aged ≥12 years and receiving voxelotor from December 2019 to May 2020 were obtained from the Symphony Health claims dataset. For each patient, the date of the first voxelotor claim was defined as the "index date." Patients with at least 1 year's data prior to the index date were included in the analyses. Patients' demographic and clinical characteristics were summarized descriptively. Standardized annualized rates of transfusions and VOCs per patient per year (PPPY) prior to and after voxelotor initiation were compared. A subset of patients in the Symphony Health claims dataset had Hb lab data available. Patients with at least 1 Hb result within 30 days prior to the index date and at least 1 Hb result after the index date were included for Hb analyses. For these patients, change in Hb and the percentage of patients achieving a >1 g/dL increase in Hb were summarized. Confidence intervals and P values for changes in outcomes were based on bootstrapping. Results: As of May 31, 2020, 1275 patients from the Symphony Health claims datasets were identified who received voxelotor (40% male, mean age 35.7 years). In the year prior to voxelotor initiation, 715 (56.1%) of these patients received hydroxyurea, 121 (9.5%) received L-glutamine, 166 (13.0%) received at least 1 transfusion, 17 (1.3%) were on chronic transfusion (≥8 transfusions per year), and 681 (53.4%) had 1 or more VOCs. Mean (SD) follow-up was 64.9 (40.7) days. Among 1275 patients, 175 and 52 patients had at least 1 Hb level measurement during the 1 year prior to and after voxelotor initiation, respectively. Among the subset of patients with their Hb level tested within 30 days prior to the index date and at least 1 Hb level after index date (n=22), the baseline average Hb level was 8.0 g/dL (SD 1.4, median 7.9 g/dL, range 5.0-11.8 g/dL). Mean increase in Hb from baseline was 1.1-1.3 g/dL (Table 1) depending on the approach used to calculate Hb levels after voxelotor initiation; 55% (95% CI 32%-77%) of patients achieved a Hb increase >1 g/dL after voxelotor initiation. Among all 1275 patients, mean (SD) overall transfusion rates declined from 0.45 (1.67) PPPY pre-index to 0.31 (1.88) post-index, a change of -0.14 PPPY (P=0.005). Among 169 patients who received at least 1 transfusion in the year prior to initiation of voxelotor, the transfusion rate dropped from 3.39 (3.34) to 1.75 (4.30) PPPY, a change of -1.64 PPPY (P<0.001). Among 17 patients receiving chronic transfusions, the transfusion rate dropped from 11.29 (3.12) to 6.74 (7.37) PPPY, a change of -4.56 PPPY (P=0.013) (Table 2). After voxelotor initiation, the annualized rates of VOC were numerically reduced from 3.86 (6.69) to 3.64 (8.54) (P=0.248). To address the potential bias from the relatively short follow-up duration, similar results of transfusion and VOC rates were observed among patients with at least 30 days of follow-up or when only events within 3 months prior to index date were considered. Conclusions: Based on the first 6 months' data after the approval of voxelotor in the US, in real-world practice, voxelotor increases Hb by at least 1 g/dL, consistent with the HOPE randomized controlled trial results. Evidence suggests that transfusion rates decreased after voxelotor initiation. A favorable downward trend in VOC rates was also observed. This real-world evidence provides additional support for the use of this novel therapy in the treatment of hemolytic anemia and its associated complications in the SCD population. Further evaluation with a larger sample size and longer follow-up will help to confirm these findings. Disclosures Zaidi: Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria; Cyclerion: Consultancy, Honoraria; Imara: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; Emmaus Life Sciences: Consultancy, Honoraria. Alvarez:Novartis: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees. Lonshteyn:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Weycker:Policy Analysis Inc.: Current Employment, Current equity holder in publicly-traded company; Novartis: Research Funding; Global Blood Therapeutics: Research Funding. Pham:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Delea:Global Blood Therapeutics: Research Funding; Novartis: Research Funding; Policy Analysis Inc.: Current Employment, Current equity holder in private company. Agodoa:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Cong:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Alexion: Speakers Bureau; Bluebird Bio: Consultancy.

scholarly journals First Results from a Nationwide Prospective Non-Interventional Study of Venetoclax-Based 1st Line Therapies in Patients with Acute Myeloid Leukemia (AML) - Revive Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Ofir Wolach ◽  
Itai Levi ◽  
Jonathan Canaani ◽  
Tamar Tadmor ◽  
Sigal Tavor ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Performance Status ◽  
Hypomethylating Agents ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Related Factors ◽  
Real World Setting

Background: The outcome of elderly patients with Acute Myeloid Leukemia (AML) is poor and treatment options in these high-risk groups are limited. Recently, venetoclax combinations with hypomethylating agents or low dose cytarabine were approved to treat patients with AML ineligible for intensive chemotherapy. However limited prospective data is available on the safety and efficacy of venetoclax treatment in routine clinical practice. Israel is among the first countries to have approved venetoclax-based combinations as first line therapy for AML and this treatment is fully reimbursed via the national health system. Here we present the initial results of a prospective, multicenter, nationwide trial that sought to assess the use of venetoclax-based therapy in a real-world setting. Methods: A prospective observational nationwide multicenter trial. Newly diagnosed patients with AML were enrolled at the time of venetoclax-based therapy initiation. Demographic, clinical and patient-related baseline characteristics were documented. Treatment patterns, safety and efficacy outcomes are reported. Patient related outcomes were assessed at baseline and after cycle 3 using the EQ-5D-5L and EORTC QLQ-C30 questionnaires. Results: A total of 70 patients were enrolled between August 2019 and June 2020 (data cut off) with a median age of 75 years (range 45-88) and a median follow-up of 74 days (8-232). Two-thirds of patients were males (62.9%). Over one-quarter (28.6%) of patients had an ECOG performance status of 2 or higher; the median modified Charlson Comorbidity Index (CCI) was 0 (range 1-4) with 27.1% with a CCI ≥2. De-novo AML was documented in 44.3%, secondary AML was diagnosed in 52.8% (secondary to MDS (27.1%), MPNs (11.4%) and therapy related AML (14.3%)). European LeukemiaNet (ELN) risk category was favorable, intermediate and adverse in 8.6%, 30% and 42.9%, respectively (Table 1). Time from diagnosis to initiation of therapy was 8 days (median, range 1-38). The main reasons for choosing venetoclax-based low intensity therapy as reported by treating physicians were patient related factors (mainly age>75 years, performance status) in the majority of cases and adverse disease biology predicting poor response to intensive chemotherapy in 17.1%. Of the 57 patients with available data, 38 (67%) initiated therapy in an inpatient setting with a median hospitalization duration of 12 days (range 1-62 days) and 19 (33%) patients started therapy as outpatients. By data cutoff, of 63 patients that initiated therapy 45, 23 and 7 patients completed cycle 1, cycle 3 and cycle 6 assessments, respectively. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 23/44 (52.3%) patients that were assessed for best response. Of responding patients, 6 (23%, 5 CRi and 1 Partial Remission (PR)) went on to receive an allogeneic transplantation (median age 70.5 years). Ninety percent of patients received venetoclax in combination with hypomethylating agents (azacytidine n=56, decitabine n=1). The full dose of 400mg was administered in 87% of cases with a median ramp-up duration of 3 days. Dose interruptions, dose modifications and dose discontinuations during follow-up were frequent and occurred in 41%, 35% and 27%, respectively. During therapy 63.5% of patients experienced adverse events (AE) of any grade; severe AE's were recorded in 41.3% of patients. Febrile neutropenia was documented in 22.2% and Tumor Lysis Syndrome (TLS) was documented in 2 patients (grade 2; 3.2%). Early death rates at 30 and 60 days were 6.3% and 11.1%, respectively. Conclusion: In the real-world setting venetoclax-based therapies are effective and associated with manageable toxicity including in the outpatient setting. In routine practice patient-related factors and disease-related factors (disease-risk) both seem to play a role in choice of therapy. Venetoclax treatment in real-life practice in Israel appears to follow general recommendations, is tolerable with approximately 90% of patients achieving target dose. These observational data are expected to provide information on patient selection patterns, efficacy and safety and patient related outcomes in patients not in clinical trial. Table Disclosures Wolach: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy. Levi:Abbvie Inc: Consultancy, Research Funding. Canaani:Abbvie: Consultancy, Honoraria, Research Funding. Tadmor:AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; Neopharm: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Tavor:Abbvie: Consultancy, Honoraria, Research Funding. Hellmann:Abbvie: Research Funding. Stemer:Abbvie: Research Funding. Cohen:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Afik:Abbvie Inc: Current equity holder in publicly-traded company. Ofek:Abbvie Inc: Current Employment. Banayan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Kan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Grunspan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Ofran:AbbVie: Membership on an entity's Board of Directors or advisory committees. Moshe:Astellas: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding.

scholarly journals Disease Burden Impacts Outcomes in Pediatric and Young Adult B-Cell Acute Lymphoblastic Leukemia after Commercial Tisagenlecleucel: Results from the Pediatric Real World CAR Consortium (PRWCC)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Liora M. Schultz ◽  
Christina Baggott ◽  
Snehit Prabhu ◽  
Holly Pacenta ◽  
Christine L Phillips ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Disease Burden ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Car T

Introduction: Chimeric Antigen Receptor (CAR) T cell therapy targeting CD19 has shifted our treatment approach for relapsed and refractory (r/r) pediatric B cell acute lymphoblastic leukemia (ALL). The landmark ELIANA pediatric trial studying tisagenlecleucel, CD19-specific CAR T cells, demonstrated a complete response (CR) rate of 81% in 75 infused patients and 12 month overall survival (OS) and event-free survival (EFS) rates of 76% and 50% respectively. Cytokine release syndrome (CRS) and neurotoxicity rates of 77% and 40% were respectively reported. In August 2017, the FDA approved tisagenlecleucel for B-cell ALL that is refractory or in second or greater relapse in patients up to age 25. With CAR commercialization, institutions deliver tisagenlecleucel without the regulation of a clinical study and practices relating to CAR delivery and reporting remain heterogeneous. Here, we report real world clinical outcomes using commercially available tisagenlecleucel for pediatric r/r B-ALL. Methods and Results: Retrospective data were collected from PRWCC member institutions (n=15) and included 200 patients. This includes 15 (7.5%) patients not infused due to manufacturing failure (n=6), death from disease progression and/or toxicity (n=7), or physician discretion following disease remission from prior therapy(n=2). The remaining 185 patients (92.5%) were infused with tisagenlecleucel, including 87% (161) receiving standard-of-care CAR T cell products meeting manufacturing release criteria and 13% (24) receiving CD19-CAR T cells manufactured by Novartis and provided on the managed access program (NCT03601442; n=14) or with single-patient IND approval (n=10). At time of CAR T cell infusion, median age was 12 years (range 0-26) with 40% females and 60% males. Median duration of follow-up at time of analysis was 11.2 months (range 0.2-28.8). The CR rate at 1 month follow up was 79% (156/198) on an intent-to-treat basis and 85% (156/184) among evaluable infused patients. Of infused patients achieving morphologic CR with available testing, 97% (148/153) were negative for MRD by flow cytometry. Duration of remission at 6 and 12 months among patients who achieved CR was 75% and 63% respectively, with 35% (55/156) of responders experiencing relapse. At time of relapse, 41% (21/51) of evaluable patients had relapse with CD19- disease and 59% (30/51) had continued CD19 expression. OS and EFS rates were 85% and 64% at 6 months and 72% and 51% at 12 months, respectively. CRS and neurotoxicity of any grade were seen in 60% (111/184) and 22% (39/181) of evaluable patients with ≥ grade 3 CRS and neurotoxicity rates of 19% (35/184) and 7% (12/181) respectively. One grade 5 CRS and 1 grade 5 neurotoxicity (intracranial hemorrhage) were reported. Post infusion toxicity management included tocilizumab in 26% (47/184) and systemic steroids in 14% (25/184) of patients. Among 181 infused patients with documented disease burden, 51% (95) had high burden (HB) disease , as defined by >5% bone marrow lymphoblasts, peripheral blood lymphoblasts, CNS3 status or non-CNS extramedullary (EM) site of disease; 22% (40) had low burden (LB) disease, defined by detectable disease not meeting the HB criteria; and 25% (46) had no detectable disease (NDD) at time of last evaluation prior to CAR infusion. The morphologic CR rate was lower at day 28 in HB vs. LB and NDD (74% vs. 98% and 96%) and the OS and EFS were lower among patients with HB at 6 mo [OS; 75% (HB), 94%(LB), 98% (NDD), EFS; 50% (HB), 86% (LB), 75%(NDD), p<0.0001] and 12 mo [OS; 58% (HB), 85% (LB), 95% (NDD), EFS; 34% (HB), 69%(LB), 72%(NDD), p<0.0001]. Multivariate analysis will be presented at the meeting. Conclusions: This retrospective, multi-institutional analysis describes real world outcomes using tisagenlecleucel to treat pediatric r/r B-ALL. Early responses at 1 month and OS and EFS at 6 and 12 months are comparable to reported ELIANA trial outcomes. Safety is demonstrated in this cohort with lower rates or CRS and neurotoxicity, likely related to a lower disease burden cohort. Continued relapse and decrease in OS without evident plateau is seen following 6 months post-infusion warranting expanded follow up. Comparative analysis of outcomes in patient cohorts with varying disease burden demonstrate decreased CR, EFS and OS in patients with high disease burden as compared to patients with lower disease burden or no detectable disease at last evaluation prior to CAR infusion. Disclosures Phillips: Novartis: Membership on an entity's Board of Directors or advisory committees. Stefanski:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Margossian:Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Verneris:Fate Therapeutics: Consultancy, Current equity holder in publicly-traded company; Novartis: Membership on an entity's Board of Directors or advisory committees; Bmogen: Consultancy, Current equity holder in publicly-traded company; Uptodate: Consultancy. Myers:Novartis: Consultancy, Honoraria, Other: ELIANA trial Steering Committee, Speakers Bureau. Brown:Jazz: Honoraria; Servier: Honoraria; Janssen: Consultancy; Novartis: Consultancy. Qayed:Novartis: Consultancy; Mesoblast: Consultancy. Hermiston:Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Satwani:Takeda: Consultancy; Mesoblast: Consultancy. Curran:Novartis: Consultancy, Research Funding; Mesoblast: Consultancy; Celgene: Research Funding. Mackall:Lyell Immunopharma: Consultancy, Current equity holder in private company; Nektar Therapeutics: Consultancy; NeoImmune Tech: Consultancy; Apricity Health: Consultancy, Current equity holder in private company; BMS: Consultancy; Allogene: Current equity holder in publicly-traded company. Laetsch:Cellectis: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Research Funding; Bayer: Consultancy, Research Funding.

scholarly journals Lower-Risk Myelodysplastic Syndromes: Erythropoiesis-Stimulating Agent Treatment Approaches and Outcomes in the United States

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4657-4657
Author(s):  
Kristin M. Zimmerman Savill ◽  
Ajeet Gajra ◽  
Kwanza Price ◽  
Jonathan K. Kish ◽  
Cherrishe Brown-Bickerstaff ◽  
...  
Keyword(s):  
Data Collection ◽  
Board Of Directors ◽  
Systemic Therapy ◽  
Research Funding ◽  
Patient Characteristics ◽  
Treatment Patterns ◽  
Publicly Traded ◽  
Independent Contractor ◽  
Advisory Committees

Abstract Introduction: Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, dysplasia in ≥ 1 cell line, cytogenetic and molecular abnormalities, and variable risk of progression to acute myeloid leukemia. Treatment goals for MDS classified as lower-risk (LR-MDS) include transfusion independence, improvement in hemoglobin (Hb) levels, and maintenance of or improvement in quality of life. Erythropoiesis-stimulating agents (ESAs) are the first-line (1L) treatment for anemia in most patients with LR-MDS lacking del(5q), but a proportion of patients do not respond to ESA treatment, or experience progression of anemia despite ESA treatment. The objective of this real-world analysis was to describe patient characteristics, treatment patterns (including ESA use), and outcomes in patients with LR-MDS. Methods: A retrospective, observational, US multisite, cohort study was conducted among adult patients initially diagnosed with LR-MDS between January 1, 2017 and June 25, 2020. Eligible patients had ≥ 1 year of follow-up after diagnosis (unless the patient died during this time) and did not receive luspatercept or any MDS treatment as part of a randomized, controlled trial. Community oncologists abstracted data from medical records, and descriptive statistics were used to summarize patient characteristics, treatment patterns, and outcomes. Data presented are from an interim analysis of an ongoing study; the last date of data collection for this analysis was July 6, 2021. Results: Among 125 eligible patients with LR-MDS, median follow-up time was 16 months, and 83% of patients were still alive at the time of data collection. In the 8 weeks prior to diagnosis, 54% of patients did not receive any red blood cell (RBC) or platelet transfusions, while 42% and 4% had low or moderate transfusion burden, respectively. Overall, 75% of patients were negative for del(5q), and 80% of patients were negative for ring sideroblasts (RS). At diagnosis of LR-MDS, serum erythropoietin levels were < 200 U/L in 49% of patients, ≥ 200 U/L in 25%, and unknown in 26%. In terms of disease management, 35% of patients did not receive any systemic therapy or transfusions, 14% received RBC and/or platelet transfusions, but no systemic therapy for MDS, and 50% were reported to have received ≤ 2 lines of systemic therapy following LR-MDS diagnosis (Table). Of the 42% of patients who received an ESA, 70% received an ESA for MDS as a single agent (SA) only, 15% as combination therapy only, and 8% as both SA and combination therapy. A further 8% received SA ESA followed by a non-ESA-based regimen. Among 45 patients who received SA ESA as 1L treatment, 18% went on to receive a hypomethylating agent (HMA) or immunomodulatory imide drug as an SA, or ESA combined with HMA or a granulocyte or granulocyte-macrophage colony-stimulating factor (G-CSF/GM-CSF) in a subsequent line. Among patients who received an ESA, 72% were still on ESA-based therapy at the time of data collection. Abstracting physicians reported that 17% of patients who received an ESA failed ESA treatment. Among these patients, physicians' determination of ESA failure was based on the National Comprehensive Cancer Network guidelines/International Working Group 2006 response criteria for 78% of patients, and on physicians' own clinical judgement for 22%. At data collection, ESA was still being administered to 22% of patients considered to have failed ESA treatment. Finally, 34% of those who received an ESA also received RBC transfusion(s) during ESA-based treatment and therefore were not transfusion independent for the entire duration of ESA-based treatment (Table). Conclusions: Results from this real-world cohort study indicate that over a third of patients with LR-MDS have been managed using watchful waiting only, with no systemic treatment or transfusions received; among those patients who received treatment, most received an ESA. Nearly one-fifth of patients in this study treated with an ESA were considered to have failed ESA treatment by abstracting physicians, though this proportion is likely to be higher with extended follow-up; 2 of 9 patients who failed ESA treatment were still receiving an ESA. Further research including longer follow-up is warranted to understand how patients with LR-MDS respond to different treatment regimens. Figure 1 Figure 1. Disclosures Zimmerman Savill: Cardinal Health: Current Employment; Roche/Genentech: Ended employment in the past 24 months. Gajra: Cardinal Health: Current Employment, Current equity holder in publicly-traded company. Price: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Kish: Cardinal Health: Current Employment, Current equity holder in publicly-traded company, Research Funding. Brown-Bickerstaff: Cardinal Health: Current Employment. Falkenstein: Cardinal Health: Current Employment. Miller: Cardinal Health: Current Employment. Laney: Cardinal Health: Current Employment. Mukherjee: Acceleron: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research/Independent Contractor, Research Funding; McGraw Hill: Honoraria, Other: Editor of Hematology Oncology Board Review (ongoing); Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research/Independent Contractor, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; AAMDS in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria; Eusa Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Teaching and Speaking; Jazz Pharmaceuticals: Research Funding; Bristol-Myers Squibb Co.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BioPharm: Consultancy; Partnership for Health Analytic Research: Honoraria; Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees.

scholarly journals To Treat or Not to Treat? Understanding Treatment Patterns in Patients with Lower-Risk Myelofibrosis at the Time of Enrollment in the MOST Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 49-51
Author(s):  
Rami S. Komrokji ◽  
Brady L. Stein ◽  
Robyn M. Scherber ◽  
Patricia Kalafut ◽  
Haobo Ren ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Lower Risk ◽  
Research Funding ◽  
Symptom Burden ◽  
Risk Groups ◽  
Treatment Patterns ◽  
Low Risk ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Therapy Initiation

Background: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by extramedullary hematopoiesis, bone marrow fibrosis, splenomegaly, constitutional symptoms, and diminished quality of life. Treatment decisions may involve a variety of factors including prognosis and symptomatology. Data regarding real-world disease and demographic factors that contribute to therapy initiation and choice in pts with lower risk MF are limited. This analysis of data from the ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) assessed whether these factors differ for lower risk pts who were treated vs untreated at enrollment. Methods: MOST is a longitudinal, noninterventional, prospective, observational study in pts with MF or essential thrombocythemia enrolled at clinical practices within the US. Pts included in the analysis (≥18 y), had low risk MF by the Dynamic International Prognostic Scoring System (DIPSS; Blood. 2010;115:1703), or intermediate-1 (INT-1) risk by age >65 y alone. Pt data were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Pt-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 233 pts with MF enrolled at 124 sites between 11/29/2016 and 03/29/2019, 205 were included in this analysis; 28 were excluded for being INT-1 risk for reasons other than age. Of the 205 pts, 85 (41.5%) were low- and 120 (58.5%) were INT-1 risk; 56.5% (48/85) and 59.2% (71/120), respectively, were being treated at enrollment. Pt characteristics are listed in Table 1A. Fewer low- vs INT-1 risk pts were JAK2 V617F or MPL positive, and more were CALR positive. The proportion of pts with palpable splenomegaly was similar for treated low- and INT-1 risk pts. In low risk pts, the proportion of pts with palpable splenomegaly was higher in untreated vs treated pts; whereas, in INT-1 risk pts, the opposite was observed (ie, lower proportion in untreated vs treated pts). Blood counts were generally similar across cohorts, except median leukocytes were lower for low risk treated pts and platelet counts were elevated in low- vs INT-1 risk pts. The proportion of pts with comorbidities was similar across cohorts, except for fewer cardiovascular comorbidities in low- vs INT-1 risk pts. Mean TSS was lower in low- vs INT-1 risk pts, but the proportion of pts with TSS ≥20 was greater in treated vs untreated pts in both low- and INT-1 risk groups. Fatigue was the most severe pt-reported symptom in all cohorts. Differences in mean TSS and individual symptom scores between risk groups were not significant (P > 0.05), except itching was worse among INT-1 risk pts (P=0.03). Physician-reported signs and symptoms were generally more frequent for untreated vs treated pts, irrespective of risk (all P > 0.05). Most low risk (69.4%) and INT-1 risk pts (61.2%) who were currently untreated at enrollment had not received any prior MF-directed treatment (Table 1B); the most common prior treatment among currently untreated pts was hydroxyurea (HU) in both risk groups. Of currently treated pts, HU was the most common MF-directed monotherapy at enrollment in low-risk pts, and ruxolitinib was most common in INT-1 risk pts. No low risk pts and few INT-1 risk pts were currently receiving >1 MF-directed therapy at enrollment. Conclusion: These real-world data from pts with MF enrolled in MOST show that a substantial proportion of both low- and INT-1 risk pts who had received treatment before enrollment were not being treated at the time of enrollment. Although watch-and-wait is a therapeutic option, the finding that many of these lower risk pts had in fact received prior therapies suggests an unmet need for effective and tolerable second-line treatment options. Treated pts had greater pt-reported symptom burden vs untreated pts, which suggests that high symptom burden may contribute to the decision for treatment. Prospective studies are needed to evaluate symptom burden change with therapy initiation. In this regard, future analyses of data from MOST are planned to assess the longitudinal evolution of the clinical characteristics, treatment patterns, and management of pts with MF. Disclosures Komrokji: Geron: Honoraria; Agios: Honoraria, Speakers Bureau; AbbVie: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau; Acceleron: Honoraria. Stein:Incyte: Research Funding; Kartos: Other: educational content presented; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; CTI Biopharma Corp: Research Funding; NS Pharma: Research Funding; ItalPharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding.

scholarly journals Real-World Outcomes for Standard-of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4075-4075
Author(s):  
Michel Delforge ◽  
Marie-Christiane Vekemans ◽  
Sébastien Anguille ◽  
Julien Depaus ◽  
Nathalie Meuleman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Retrospective Chart Review ◽  
Standard Of Care ◽  
Real World Data ◽  
Advisory Committees ◽  
Treatment Regimens

Abstract Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p<0.001), being male (p=0.001), older age (p<0.001), shorter duration of prior lines (p<0.001), shorter time to progression in prior line (p=0.025), and higher LDH levels (p<0.002) were prognostic for worse outcomes for both OS (Figure 1) and PFS. Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of <10 months. A wide variety of treatment regimens used in clinical practice confirm the absence of a clear standard-of-care in this patient population. The literature also confirms that these poor outcomes observed in Belgium, for this subset of MM patients, are similar in other countries. These real-world data highlight the high unmet medical need in this patient population and critical need for new and effective treatment options. MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

scholarly journals Real-World Outcomes for Pediatric and Young Adult Patients with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL) Treated with Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 428-428
Author(s):  
Samuel John ◽  
Michael A. Pulsipher ◽  
Amy Moskop ◽  
Zhen-Huan Hu ◽  
Christine L. Phillips ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Ad Hoc ◽  
Age Groups ◽  
Advisory Committees ◽  
Advisory Boards

Abstract Background: Tisagenlecleucel is an autologous CD19-directed T-cell immunotherapy indicated in the USA for treatment of patients up to 25 years (y) of age with B-cell ALL that is refractory or in second or later relapse. Overall response rate was 82% with 24 months' (mo) follow-up in the registrational ELIANA trial [Grupp et al. Blood 2018]; pooled data from ELIANA and ENSIGN revealed similar outcomes upon stratification by age (<18y and ≥18y) [Rives et al. HemaSphere 2018]. Early real-world data for tisagenlecleucel from the CIBMTR registry reported similar efficacy to ELIANA with no new safety signals [Pasquini et al. Blood Adv 2020]. Outcomes are reported here for patients who received tisagenlecleucel in the real-world setting, stratified by age (<18y and ≥18y). Methods: This noninterventional prospective study used data from the CIBMTR registry and included patients aged ≤25y with R/R ALL. Eligible patients received commercial tisagenlecleucel after August 30, 2017, in the USA or Canada. Age-specific analyses were conducted in patients aged <18y and ≥18y at the time of infusion. Efficacy was assessed in patients with ≥12mo follow-up at each reporting center and included best overall response (BOR) of complete remission (CR), duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). Safety was evaluated in all patients who completed the first (100-day) assessment. Adverse events (AEs) of interest - including cytokine release syndrome (CRS) and neurotoxicity - were monitored throughout the reporting period. CRS and neurotoxicity were graded using the ASTCT criteria. Results: As of October 30, 2020, data from 451 patients were collected, all of whom received tisagenlecleucel. The median time from receipt of leukapheresis product at the manufacturing site to shipment was 27 days (interquartile range: 25-34). Patients aged ≥18y appeared to have greater disease burden at baseline than those aged <18y, indicated by lower rates of morphologic CR and minimal residual disease (MRD) negativity prior to infusion. Older patients were also more heavily pre-treated before infusion. All other patient characteristics at baseline were comparable between the two groups (Table 1). In the efficacy set (median follow-up 21.5mo; range 11.9-37.2; N=322), BOR of CR was 87.3% (95% CI 83.1-90.7); MRD status was available for 150 patients, of whom 98.7% were MRD negative. Median DOR was 23.9mo (95% CI 12.3-not estimable [NE]), median EFS was 14.0mo (9.8-24.8) and median RFS was 23.9mo (13.0-NE); 12mo EFS and RFS were 54.3% and 62.3%, respectively. For OS, the median was not reached. Efficacy outcomes were generally similar across age groups (Table 1). In the safety set (median follow-up 20.0mo; range 2.6-37.2; N=400), most AEs of interest occurred within 100 days of infusion. Any-grade CRS was observed in 58.0% of patients; Grade ≥3 in 17.8%. Treatment for CRS included tocilizumab (n=113; 28.3% of all patients) and corticosteroids (n=31; 7.8%). Neurotoxicity was observed in 27.3% of patients; Grade ≥3 in 10.0%. Treatment for neurotoxicity included tocilizumab (n=17; 4.3% of all patients) and corticosteroids (n=28; 7.0%). During the reporting period, 82 (20.5%) patients died; the most common cause of death was recurrence/persistence/progression of primary disease. CRS and chimeric antigen receptor (CAR)-T cell-related encephalopathy syndrome were the primary cause of death in 2 patients and 1 patient, respectively. Overall, safety data were similar across age groups, although more patients aged ≥18y experienced any-grade CRS or neurotoxicity and were subsequently treated (Table 1). Conclusions: Updated registry data for pediatric and young adult patients with R/R ALL treated with tisagenlecleucel revealed that patients aged ≥18y had a greater disease burden and were more heavily pre-treated at baseline than patients aged <18y. The overall efficacy and safety profiles of commercial tisagenlecleucel reflected those observed in the clinical trial setting [Grupp et al. Blood 2018; Rives et al. HemaSphere 2018] and were broadly consistent across age groups. Some important differences between the <18y and ≥18y groups were identified, which may point to challenges in timely identification and/or referral of older patients for CAR-T cell therapy. Figure 1 Figure 1. Disclosures Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Hu: Kite/Gilead: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Phillips: Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Margossian: Cue Biopharma, Inc.: Current Employment; Novartis: Other: Ad hoc Advisory Boards. Nikiforow: Kite/Gilead: Other: Ad hoc advisory boards; Novartis: Other: Ad hoc advisory boards; Iovance: Other: Ad hoc advisory boards; GlaxoSmithKline (GSK): Other: Ad hoc advisory boards. Martin: Novartis: Other: Local PI for clinical trial; Bluebird Bio: Other: Local PI for clinical trial. Rouce: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Pfizer: Consultancy. Tiwari: Novartis Healthcare private limited: Current Employment. Redondo: Novartis: Current Employment. Willert: Novartis: Current Employment. Agarwal: Novartis Pharmaceutical Corporation: Current Employment, Current holder of individual stocks in a privately-held company. Pasquini: Kite Pharma: Research Funding; GlaxoSmithKline: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Grupp: Novartis, Roche, GSK, Humanigen, CBMG, Eureka, and Janssen/JnJ: Consultancy; Novartis, Kite, Vertex, and Servier: Research Funding; Novartis, Adaptimmune, TCR2, Cellectis, Juno, Vertex, Allogene and Cabaletta: Other: Study steering committees or scientific advisory boards; Jazz Pharmaceuticals: Consultancy, Other: Steering committee, Research Funding.

scholarly journals Final Primary Results from the Defifrance Registry Study: Effectiveness and Safety of Defibrotide in the Treatment of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Mohamad Mohty ◽  
Ibrahim Yakoub-Agha ◽  
Myriam Labopin ◽  
Didier Blaise ◽  
Delphine Lebon ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Sinusoidal Obstruction Syndrome ◽  
Publicly Traded ◽  
Real World Data ◽  
Advisory Committees ◽  
World Data

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication that occurs after hematopoietic cell transplantation (HCT) conditioning. In its most severe form, VOD/SOS is associated with multi-organ failure (MOF) and a mortality rate of >80% if untreated. Defibrotide is approved for the treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in adult and pediatric patients in the United States and severe hepatic VOD/SOS post-HCT in patients aged >1 month in the European Union. The DEFIFrance study collected real-world data on the safety and effectiveness of defibrotide in France. This analysis presents final primary data on the subgroup of DEFIFrance patients who received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT. This post-marketing study collected retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centers in France from July 15, 2014 to March 31, 2020. VOD/SOS severity was categorized using European Society for Blood and Marrow Transplantation criteria (adults) or study steering committee member adjudication (pediatric patients). The primary endpoints included Kaplan-Meier (KM)-estimated Day 100 (post-HCT) survival and Day 100 complete response (CR; total serum bilirubin <2 mg/dL and MOF resolution per investigators' assessment) in patients with severe/very severe VOD/SOS post-HCT. Secondary endpoints included evaluation of adverse events (AEs) of interest, such as hemorrhage, coagulopathy, injection-site reactions, infections, and thromboembolic events, irrespective of their relationship to treatment. Of the 775 defibrotide-treated patients included in the study analysis, 250 received defibrotide for the treatment of severe/very severe VOD/SOS post-HCT (severe: 119 [48%]; very severe: 131 [52%]). The median patient age was 45 years (range: 5 months, 74 years) and 52 (21%) patients were less than 18 years of age. A total of 219 (88%) patients had received allogeneic HCT and 95 (38%) patients had an unrelated donor. The Day 100 KM-estimated survival was 58% (95% confidence interval [CI]: 52%, 64%) in patients with severe/very severe VOD/SOS post-HCT. The estimated Day 100 survival rate was higher in patients with severe (74% [95% CI: 65%, 81%]) versus very severe (43% [95% CI: 35%, 52%]) VOD/SOS. Among patients with severe/very severe VOD/SOS post-HCT, the CR rate at Day 100 was 53% (95% CI: 47%, 59%). The Day 100 CR rate was higher in patients with severe (68% [95% CI: 60%, 77%]) versus very severe (39% [95% CI: 30%, 47%]) VOD/SOS. Treatment emergent AEs of interest occurred in 41% of patients with severe/very severe VOD/SOS, with infection (23%) and bleeding (17%) being the most commonly reported. The DEFIFrance study represents the largest collection of real-world data on the use of defibrotide. The effectiveness and safety observed in this study build upon prior studies supporting the utility of defibrotide for treating severe/very severe VOD/SOS post-HCT in a real-world setting. Among patients receiving defibrotide for VOD/SOS post-HCT, outcomes were better in patients with severe versus very severe disease, highlighting the importance of early diagnosis and treatment of VOD/SOS before patients reach the most severe stage of VOD/SOS. Disclosures Mohty: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria. Labopin:Jazz Pharmaceuticals: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria. Renard:Jazz Pharmaceuticals: Research Funding. Jubert:Jazz Pharmaceuticals: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Bouvatier:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Dalle:Bellicum: Consultancy, Honoraria; Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Consultancy, Honoraria; Gilead: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orchard: Consultancy, Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Peffault De Latour:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Blinatumomab in Children with Relapsed or Refractory B-Precursor Acute Lymphoblastic Leukemia (R/R-ALL): Final Results of 110 Patients Treated in an Expanded Access Study (RIALTO)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Noemi Mergen ◽  
Peter Bader ◽  
Sima Jeha ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Board Of Directors ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Final Analysis ◽  
Publicly Traded ◽  
Primary Analysis ◽  
Advisory Committees ◽  
Grade 3

Introduction: The open-label, expanded access study (RIALTO) demonstrated that blinatumomab is efficacious with a manageable safety profile in children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Blinatumomab is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that activates cytotoxic T cells to kill target B cells. Here, findings from the final analysis of RIALTO are presented (NCT02187354). Methods: Enrolled in the study were children >28 days and <18 years of age with R/R CD19+ BCP-ALL (defined as ≥2 relapses, relapse after allogeneic hematopoietic stem cell transplant [alloHSCT], or refractory to prior treatments) and ≥5% blasts or <5% blasts but with minimal residual disease (MRD) level ≥10−3. Blinatumomab was given as continuous infusion in a 6-week cycle (4 weeks on and 2 weeks off) for up to 5 cycles and safety follow-up visit 30 days post-treatment. Patients with <25% blasts were dosed at 15 µg/m2/day, whereas those with ≥25% blasts were dosed at 5 µg/m2/day (days 1-7 of cycle 1) followed by dose increase to 15 µg/m2/day. Primary endpoint was incidence of treatment-emergent (TE) and treatment-related (TR) adverse events (AEs). Secondary endpoints included complete response (CR; <5% blasts) and MRD response (<10−4 blasts by PCR or flow-cytometry) in the first 2 cycles, relapse-free survival (RFS), overall survival (OS), and alloHSCT rate after blinatumomab treatment. Results: As of the data cutoff date (January 10, 2020) for the final analysis, demographics and baseline characteristics of 110 patients enrolled (median age, 8.5 years [95% CI 0.4-17.0]), 61% had <50% blasts at baseline, and 11% had <5% blasts (n=12; with MRD ≥10−3) remain unchanged compared with the primary analysis (Table 1). For best treatment response within the first 2 cycles, results are comparable to that of the primary analysis. Among 110 patients, overall CR rate was 62.7% (n= 69). Of 98 patients with ≥5% blasts at baseline, 59% (n=58) achieved CR; of them, 79% (n=46) achieved an MRD response and 62% (n=39) proceeded to HSCT. The 2 patients with t(17;19) achieved CR with an MRD response. Of the 4 patients with germline trisomy 21 (Down syndrome), 3 achieved CR with an MRD response Among the 12 patients with <5% blasts but with MRD ≥10−3 at baseline, 92% (n=11) achieved CR and MRD response; 75% (n=9) proceeded to HSCT (Table 2). Of the 5 patients who had received prior blinatumomab , 4 achieved CR. Of 110 patients treated with blinatumomab, median OS (95% CI) was 14.6 (11-24.5) months with median follow-up time of 18.2 months, which increased by 1.5 months compared with that reported in the primary analysis, with 29.9% of patients still surviving at month 24. Median RFS (95% CI) remains unchanged at 8.5 months (4.7-14.0), with a median follow-up time of 11.5 months in patients who achieved CR; 38% of patients relapsed and 9% died. RFS was more favorable for patients who received HSCT post blinatumomab (70%) than for those who did not (30%) at month 12, respectively, which is consistent with the results from primary analysis. Among patients who had HSCT prior to blinatumomab (n= 45), median OS (95%) was 16.6 (7.1-NE) months vs 14.6 (10.9-24.5) months in patients without HSCT prior to blinatumomab (n= 65). Compared with the primary analysis, 5 additional patients received HSCT after achieving CR in the final analysis. Median OS among patients in CR after HSCT by MRD responders vs MRD non-responders was NE at 15-month analysis (Figure). Safety results in the final analysis were consistent with those reported in the primary analysis. Of 110 patients, 99% experienced TEAEs, with 65% being grade ≥3 (see Table 3 for details). TRAEs were reported in 74% of patients; 26% were grade ≥3 and 19% were deemed serious. Details on grade ≥3 TRAEs are shown in Table 3. The 9 fatal AEs, unrelated to blinatumomab, occurred due to relapse and progressive nature of the disease (Table 3). Conclusions: Overall, the safety and efficacy results from the final analysis are consistent with those reported in the primary analysis as no new safety signals were observed. These findings strengthen the observation that blinatumomab demonstrates durable efficacy and is a suitable treatment option in children with R/R BCP-ALL. Table 1. Disclosures Locatelli: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Speakers Bureau; Miltenyi: Speakers Bureau; Bellicum Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceeutical: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zugmaier:Amgen: Current Employment, Other: Personal Fees ; 20190300609: Patents & Royalties: Licensed patient . Mergen:Amgen: Current Employment, Current equity holder in publicly-traded company. Bader:Medac: Patents & Royalties, Research Funding; Amgen: Consultancy, Speakers Bureau; Neovii: Research Funding; Celgene: Consultancy; Novartis: Consultancy, Speakers Bureau; Riemser: Research Funding. Schlegel:bluebird bio: Honoraria. Bourquin:Servier: Other: Travel Support. Handgretinger:Amgen: Honoraria. Brethon:Amgen: Other: invitation to meetings, remunerations for oral presentations, advices for the record of Blinatumomab in pediatrics in France. Rössig:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Pfizer: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Kormany:Amgen: Current Employment, Current equity holder in publicly-traded company. Viswagnachar:IQVIA: Current Employment.

Real World Evidence of Prescription Patterns and Effect of Oxbryta (voxelotor) for Patients with Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Nirmish Shah ◽  
Ahmar Urooj Zaidi ◽  
Michael U. Callaghan ◽  
Darla Liles ◽  
Clarissa E. Johnson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Real World ◽  
Research Funding ◽  
Cell Disease ◽  
Advisory Committees ◽  
Real World Evidence ◽  
Disease Modifying

Background: Sickle cell disease (SCD) is a chronic illness characterized by anemia, recurrent severe pain and recurrent organ damage, affecting approximately 100,000 persons in the United States. Prior to November 2019, FDA approved SCD disease-modifying treatments included only hydroxyurea (HU) and L-glutamine. However, voxelotor (Oxbryta®) was recently approved under an accelerated approval based on the HOPE study for the treatment of adult and pediatric patients with SCD 12 years of age and older. We aimed to provide real world evidence of the types of patients prescribed voxelotor and preliminary evidence of potential treatment effects. Methods: Patient records were reviewed from five medical centers with comprehensive sickle cell care. All patients prescribed voxelotor from Nov 25, 2019 to July 31, 2020 were included in our analysis. Data reviewed included: patient demographics, hydroxyurea use, as well as pre- and post- voxelotor changes on red cell transfusion number, vaso-occlusive crisis (VOC) and hemoglobin (Hb) values. In addition, voxelotor dosage changes, side effects, and patients perception on impact on their health were recorded. Descriptive and summary statistics were used to provide results. Results: We reviewed data from 60 patients (18 pediatric and 42 adult), across the five centers, who were prescribed voxelotor. Mean age was 33 (SD 13.8) years old with 63% female patients. All patients were African-American/Black and 96% were HbSS (2% Hb SC and 2% HbSOArab). Eighty (80)% were on hydroxyurea, 20% were on chronic transfusions, and 10% were on erythropoietin stimulating agents when prescribed voxelotor. Mean baseline hemoglobin during the 3 months prior to initiation was 7.38 g/dL (SD 1.46) with all patients started at the recommended dose of 1500mg. Annualized VOC events for the year prior to starting voxelotor was 0.62 (SD) or 7.44 VOCs per year. Across all sites, 31 patients were prescribed voxelotor but had either not initiated drug, not returned for follow up labs at time of analysis, or refused to take drug once approved (n=1). Nine patients had only 1 month of follow labs to review and an additional 18 patients with 3 months of follow up labs. These 27 patients were followed for an average of 6.0 months (SD 7.7) on treatment with 4 patients (15%) requiring dose adjustment to 1000mg. Dose adjustments were for side effects including abdominal pain, diarrhea, loose stools and nausea/vomiting. One patient had dosing changed from daily to three times a day. Average hemoglobin during steady state after 1 and 3 months of treatment were 8.6 g/dL (SD 1.8) and 8.0 g/dL (SD 1.8), respectively. In addition, 52% increased by 1g/dL at 1 month (n=21) and 44% increased by 1g/dL at 3 months (n=18). The mean maximum hemoglobin obtained during the 3-month period following initiation of voxelotor was 8.9 (SD 2.1) g/dL. During follow up visits, several patients reported 'more energy' and improvement in 'morning achiness' and 'quality of life', while a few patients noted no change in stamina or well-being. Three patients (5%) had drug discontinued due to becoming pregnant, unexplained elevation of liver enzymes, and due to excessive abdominal pain and nausea. Annualized VOC rates after voxelotor initiation were numerically decreased, although limited by short follow up. Conclusion: We present real world evidence of prescribing patterns and initial outcomes from the use of newly approved voxelotor. We found the majority of patients prescribed voxelotor were the HbSS genotype, on hydroxyurea, and with a mean baseline Hb <7.5 g/dL, indicating an initial focus on more anemic patients. Interestingly, one-fifth of the prescribed patients where on chronic transfusions. Consistent with the HOPE trial, the average Hb levels was found to have increased at 1 month and 3-month follow up. Our preliminary results support an overall increase in hemoglobin in patients treated with voxelotor and we aim to continue following patients over a longer follow up period. This provides important real-world evidence for this newly approved disease-modifying therapy for SCD. Disclosures Shah: Alexion: Speakers Bureau; CSL Behring: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; Bluebird Bio: Consultancy. Zaidi:Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Emmaus Life Sciences: Consultancy, Honoraria; Imara: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; Cyclerion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Callaghan:Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Research Funding; Sancillio: Other; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NovoNordisk: Other, Speakers Bureau; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Alnylum: Current equity holder in publicly-traded company; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Hema Biologics: Honoraria, Membership on an entity's Board of Directors or advisory committees. De Castro:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlycoMimetics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Sign in / Sign up

Export Citation Format

Share Document