scholarly journals Treatment Patterns and Outcomes of Multiple Myeloma (MM) with Chromosome Translocation (11;14) in United States (US) Routine Clinical Practice

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 40-43
Author(s):  
Shebli Atrash ◽  
Evelyn M. Flahavan ◽  
Tao Xu ◽  
Esprit Ma ◽  
Sudeep Karve ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Community Setting ◽  
B Cell Lymphoma ◽  
Chromosome Translocation ◽  
Routine Clinical Practice ◽  
Chromosome 1 ◽  
Test Results ◽  
Publicly Traded ◽  
The Us

Introduction: MM is an incurable disease with risk categorizations by cytogenetic abnormalities. Prognostic implications of chromosome translocation t(11;14)+ are important to inform development of biomarker-targeted therapies such as the B-cell lymphoma-2 (BCL-2) pathway inhibitors. This study aims to evaluate MM treatment (Tx) patterns and outcomes of t(11;14)+ compared with other cytogenetic cohorts in US routine clinical practice. Methods: A retrospective observational cohort study of the Flatiron Health database, which comprises de-identified electronic health record-derived patient (pt)-level data from over 280 community and academic cancer clinics in the US. Pts aged ≥18 years who received a first-line (1L) induction Tx within ≤60 days of MM diagnosis from 1/1/2011 to 1/31/2020, and were not enrolled in a clinical trial were identified at the start of each Tx line (index date) and followed up (f/u) until 1/31/2020. Only cytogenetic results by fluorescence in situ hybridization (FISH) were used to stratify the cohort into: t(11;14)+; standard risk, excluding t(11;14)+ (SR); and high risk, (HR; del 17p, t(4;14), t(14;16), t(14;20), chromosome 1 abnormalities as a proxy for 1q gain; and t(11;14) where it co-occurs). Descriptive analyses of pt characteristics and Tx were conducted. Kaplan-Meier analyses were used to evaluate median time to next treatment (TTNT) and overall survival (OS) with log-rank test for significance. The cohort was stratified by age ≤70/>70 years (yrs) as a proxy for transplant eligibility. Results: Of 10,703 pts with MM in the database, 5982, 3059 and 1595 pts were eligible for 1L, second-line (2L), and third-line (3L) analysis, of which 76%, 84%, and 86%, respectively, had FISH test results before Tx initiation. 14% of pts with FISH test results were t(11;14)+, ~55% SR and ~35% HR. Included pts were predominately male (55%), ~90% treated in the community setting and ~16% African-American. Pts in the 3L cohort were younger at diagnosis with a median age (interquartile range) of 67 (59 ̶ 74) yrs compared with 69 (61 ̶ 76) yrs in both 1L and 2L. The 1L Tx pattern was consistent across cytogenetic cohorts with bortezomib (V), lenalidomide (R), dexamethasone (d) as the most common Tx (>42%). Together, VRd, Rd, Vd, and cyclophosphamide (Cy) in combination with Vd represented ≥90% of 1L Tx (Figure 1). Across 2L cytogenetic cohorts, the most common Tx regimens (≥25%) were VRd and Rd. The use of regimens containing carfilzomib (K) and daratumumab (D) was emerging in 2L: KRd in 8% of t(11;14)+ and HR and 5% in SR; Kd 5% in all groups; DRd in 4% of t(11;14)+ and 3% in SR and HR (Figure 1). 3L Tx pattern was fragmented with different Tx regimens. Rd was the most common 3L Tx option: 9% in t(11;14)+, 10% in SR and 7% in HR (Figure 1). Across all lines of Tx, t(11;14)+ had similar Tx outcomes to SR, and HR had poorest outcomes (Table 1). Pts TTNT shortened as they advanced to later lines of Tx (Table 1). Although TTNT did not differ by age across lines of Tx, OS was superior in pts <70 yrs across all 3 cytogenetic risk cohorts, especially in 1L where transplant in those ≤70 yrs vs >70 yrs at diagnosis was 44% vs 11% for t(11;14)+, 47% vs 10% for SR and 49% vs 9% for HR. Conclusions: This study identified cytogenetic subgroups across 1L to 3L in a predominately community setting in the US. MM t(11;14)+ pts had similar 1L and 2L Tx patterns to SR and HR. Across all lines of Tx, the outcomes of t(11;14)+ and SR pts were comparable and better than HR pts. TTNT was reduced as pts advanced to later lines of Tx. Pts continuing to 3L Tx were younger at diagnosis, but there was not a clear-cut standard of care. While TTNT did not differ by age across lines of Tx, OS was superior in pts <70 yrs across all 3 cytogenetic risk cohorts. This study sets the benchmark for novel treatment options, such as BCL-2 pathway inhibitors, primarily wherever available biomarker-driven therapy is considered appropriate. Disclosures Atrash: Takeda, Amgen, Karyopharm, BMS, Sanofi, Cellactar, Janssen and Celgene: Honoraria; BMS, Jansen oncology, Sanofi: Speakers Bureau; Amgen, GSK, Karyopharm.: Research Funding. Flahavan:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Roche Products Ltd.: Current Employment. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Karve:AbbVie: Current Employment, Current equity holder in publicly-traded company. Hong:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Jirau-Lucca:Genentech, Inc.: Current Employment; AbbVie: Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company; Celgene: Divested equity in a private or publicly-traded company in the past 24 months. Nixon:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Ailawadhi:Takeda: Honoraria; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding; Amgen: Research Funding; Celgene: Honoraria; Janssen: Research Funding.

scholarly journals Treatment Patterns and Outcomes of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Hypomethylating Agents (HMA) in the United States (US)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-16
Author(s):  
Timothy S. Pardee ◽  
Jessica Oschwald ◽  
Esprit Ma ◽  
Tao Xu ◽  
Melissa Montez ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Community Setting ◽  
Patient Characteristics ◽  
Treatment Patterns ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
The Past ◽  
The Us

Introduction: AML is an aggressive disease with poor prognosis that predominantly affects older adults. Due to advanced age and associated comorbidities, many patients are not fit for intensive induction chemotherapy. Monotherapy with HMAs such as azacitidine (AZA) or decitabine (DEC) is often still considered as standard of care for these patients, despite mixed evidence from studies regarding the benefit of HMAs alone (Duchmann & Itzykson. Int J Hematol 2019). The aim of the current study is to evaluate patient characteristics, treatment patterns and outcomes of patients with AML treated with HMA monotherapy as first line (1L) in clinical practice in the US. Methods: This is a retrospective observational study of the Flatiron Health database; a nationwide, longitudinal, demographically and geographically diverse database representing more than 2.4 million patients with cancer in the US. The database contains de-identified data derived from electronic health records from over 280 cancer clinics, which are predominantly community oncology practices. Patients ≥18 years, diagnosed with AML between 1/1/2014 and 3/30/2020 (excluding acute promyelocytic leukemia and clinical trial enrollment), and who received HMAs as 1L treatment ≤30 days from AML diagnosis were evaluated. Descriptive analyses were conducted on patient characteristics and treatment patterns. Kaplan-Meier analyses were used to estimate time to last administration (TTLA; from initiation to last observed administration before death, end of follow-up or a gap of 60 days) and median overall survival (OS). Results: A total of 2589 patients with an AML diagnosis were included for analysis, where 574 (22%) were treated with 1L HMAs (AZA: n=341 [59%]; DEC: n=233 [41%]). The median age of 1L HMA patients was 79 years with 63% male. Most patients were treated in the community setting (n=511 [89%]; median age: 79 years); those treated in academic centers were slightly younger (n=63 [11%]; median age: 77 years). Characteristics for non-antecedent hematological disorder (AHD)-AML (n=327) and AHD-AML (n=247) patients are presented in Table 1. Median TTLA with 1L HMA was 77 days with a median of 3 cycles of both AZA and DEC. Of the 168 patients who received second-line (2L) therapy, 82% (n=138) received another low-intensity therapy or combination (of which only 14 received targeted therapies) (Figure 1). Overall, 44% of 1L HMA patients (n=254) had evidence of molecular testing before 1L treatment initiation (this was more common in later years). Of the 228 patients tested for FLT3, 30 (13%) were FLT3 positive; 7 (23%) FLT3-positive patients were treated with 2L or third-line (3L) FLT3-targeted therapies (gilteritinib, midostaurin or sorafenib). Of the 152 patients tested for IDH1/2, 35 (23%) were IDH1/2 positive; 5 (14%) IDH1/2-positive patients were treated with 2L or 3L targeted agents (enasidenib or ivosidenib). A median OS of 6.3 months (95% CI: 5.5-7.5) was observed in the overall 1L HMA cohort. Median OS in 1L HMA patients did not differ with respect to different types of AML (non-AHD-AML: 6.6 [95% CI: 5.5-7.9] months; AHD-AML: 6.0 [95% CI: 4.8-7.5] months, p=0.34) or practice setting (community: 6.0 [95% CI: 5.3-7.0] months; academic: 8.3 [95% CI: 6.9-13.3] months, p=0.14). One-year OS was 31.4% and 30.1% for non-AHD-AML and AHD-AML patients, respectively. Patients treated in the community setting had numerically lower 1-year OS (29.7% [95% CI: 25.8-34.3]) than those treated in the academic setting (39.5% [95% CI: 28.6-54.6]), which reflects the higher rates of 2L treatment in academic practice, though this analysis is unadjusted. Conclusions: This new database enabled a detailed analysis of 1L HMA-treated patients with newly diagnosed AML in routine clinical practice predominantly in the community setting. 1L HMA patients have poor survival outcomes (median OS 6.3 months) which are comparable to other real-world data from SEER-Medicare (Zeidan et al. Blood Adv 2020; median OS 7-8 months; median age: 77 years); but shorter than the median OS of 9-10 months observed in 1L HMA-treated AML patients in clinical trials (DiNardo et al. EHA 2020). Limitations of the study included limited conduct of bone marrow biopsies for response and lack of transfusion data. The observed survival outcomes highlight the importance of further treatment advances to address the unmet need in older patients with AML ineligible for intensive induction chemotherapy. Disclosures Pardee: Rafael: Research Funding; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Pharmacyclics: Speakers Bureau; Rafael Pharmaceuticals: Consultancy; BMS: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy; Genentech, Inc.: Consultancy; Karyopharm: Research Funding. Oschwald:Roche Products Limited: Current Employment. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Montez:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ramsingh:Genentech, Inc.: Current Employment; NEKTAR: Current equity holder in publicly-traded company; Exelixis: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Hong:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Choi:AbbVie: Current Employment, Current equity holder in publicly-traded company. Flahavan:Roche Products Ltd.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. OffLabel Disclosure: Discussion will include the use of decitabine for the treatment of AML.

scholarly journals Cardiovascular Hospitalization in Patients Treated with Dasatinib or Nilotinib in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients in Routine Clinical Practice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4258-4258
Author(s):  
Michael J. Mauro ◽  
Clara Chen ◽  
Jorge E. Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Ginny P Sen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Hospital Stay ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Routine Clinical Practice ◽  
Kaplan Meier ◽  
The Us ◽  
Line Of Therapy

Abstract Introduction: The combined effect of cardiovascular (CV) risk and tyrosine kinase inhibitor (TKI) therapy may contribute to the incidence of CV events in patients (pts) with chronic phase chronic myeloid leukemia (CP-CML). CV events can affect the overall clinical outcomes and survival of CML patients, and hospitalization due to CV events is costly; analyzing the rates and risks of CV hospitalization in pts with CML receiving TKI therapy may help to inform treatment decisions and risk mitigation strategies and to minimize costs. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML pts in routine clinical practice receiving first-line (1L) TKIs since 2010 in the US and Europe, exploring TKI use and management patterns in clinical practice. This analysis aims to evaluate rates of CV-related hospitalization and estimate related costs in pts treated with the second-generation TKIs dasatinib (DAS) and nilotinib (NIL). Methods: CV hospitalizations were identified retrospectively from events reported by SIMPLICITY investigators over the course of treatment with DAS or NIL, from the start of treatment (any line of therapy) to 30 days after the end of that line of therapy, or prior to the start of a subsequent line of TKI therapy, whichever was sooner. Pts were followed for a maximum of five years. Owing to the observational nature of SIMPLICITY, patients were not matched between cohorts and adjustments for covariates were not made. Kaplan-Meier methods with the log-rank test were used to estimate time to first CV hospitalization. Statistical comparisons were made using t-tests and the Mann-Whitney U test for continuous variables and chi square for categorical variables. Results: Overall, 825 pts received DAS (n=417) or NIL (n=408) as 1L therapy; 376 pts received DAS (n=214) or NIL (n=162) as second-line (2L) therapy; and 124 pts received DAS (n=63) or NIL (n=61) as third-line (3L) therapy. See table for patient baseline demographics and comorbidities. No significant differences were noted between the DAS and NIL cohorts. Median age was similar between the DAS and NIL groups at 56.2 and 54.1 years. At baseline, both groups had similar CV comorbidities. A significantly greater number of pts were treated in the US vs Europe (p=0.017). Investigators reported that, during 1L DAS and NIL therapy, 43% (n=357) of pts experienced a CV disorder: 45.3% (n=189) of DAS pts and 41.2% (n=168) of NIL pts (DAS vs NIL, p=0.28). Numbers of CV-related hospitalizations occurring during DAS and NIL therapy were 16 and 36, respectively, translating to 12.6 and 27.4 CV-related hospitalizations per 1000 pt years. Across 1L, 2L, and 3L (referred to here as 'all lines') of DAS and NIL therapy, 31 and 51 CV-related hospitalizations occurred, translating to 16.7 and 28.8 CV-related hospitalizations per 1000 pt years, respectively. The three most common CV-related reasons for hospitalization were congestive cardiac failure, atrial fibrillation and myocardial infarction. The figure shows Kaplan-Meier curves of time to first CV-related hospitalization for 1L therapy, for five years of follow-up. CV-related hospitalization at 5 years of follow-up was 5% for pts on 1L DAS, 7.5% for pts on 1L NIL, 5.7% for all lines of DAS and 8.5% for all lines of NIL. Durations of hospital stay related to CV disorders for pts on 1L DAS and 1L NIL were 68 days and 263 days, translating to 53.3 and 199.8 days in hospital per 1000 pt years. Durations of hospital stay related to CV disorders for pts on all lines of DAS and NIL were 107.4 days and 226.1 days, translating to 53.3 and 199.8 days in hospital per 1000 pt years. Incremental cost differences based on mean estimates will be presented. Conclusions: CV disorders and related hospitalizations were frequently seen in patients with CP-CML in SIMPLICITY. In these patients, NIL was associated with a rate of CV hospitalization up to double that associated with DAS and lengthier hospital stay. Owing to the survival benefits conferred by TKIs, it is critical to minimize and manage complications that may arise in treated pts; potential for greater morbidity and healthcare cost should be considered when making decisions about TKIs to use in individual pts, particularly those with preexisting CV comorbidities. Disclosures Mauro: Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Novartis: Consultancy, Research Funding. Chen:Bristol-Myers Squibb: Employment. Cortes:Novartis: Consultancy, Research Funding; Arog: Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Gambacorti-Passerini:Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Sen:ICON PLC: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment. Michallet:Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.

scholarly journals Effectiveness and Safety Outcomes in Patients with Hemophilia a Receiving Antihemophilic Factor (Recombinant) for at Least 5 Years in a Real-World Setting: 6-Year Interim Analysis of the Ahead International and German Studies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Dimitrios A. Tsakiris ◽  
Johannes Oldenburg ◽  
Robert Klamroth ◽  
Benoît Guillet ◽  
Kate Khair ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Interim Analysis ◽  
Research Funding ◽  
Hemophilia A ◽  
Routine Clinical Practice ◽  
Publicly Traded ◽  
Real World Setting ◽  
Antihemophilic Factor

Introduction: Long-term effectiveness and safety data in patients treated in routine clinical practice settings can be captured from real-world studies. The international (INT) and German (GER) Antihemophilic factor (recombinant; rAHF) Hemophilia A (HA) outcome Database (AHEAD) studies assess long-term effectiveness and safety outcomes in patients with moderate HA (factor VIII level 1-5%) or severe HA (factor VIII <1%) receiving rAHF (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) in routine clinical practice. Methods: These are non-interventional, prospective, long-term, multicenter studies (INT: NCT02078427; GER: DRKS 00000556). Key outcomes include Gilbert scores (primary endpoint; pain scored 0-3; bleeding scored 0-3, and physical exam scored 0-12), annualized bleeding rates (ABRs) by disease severity, and adverse events (AEs). Findings reported here are from the 6-year interim analysis (data cut-off: July 15, 2019), and focus on patients who have received rAHF prophylaxis or on-demand (OD) treatment for ≥5 years in the studies. All data are reported for the safety analysis set (SAS), which comprised patients who passed screening and were assigned to a treatment group or regimen in the INT study, or were enrolled and have received ≥1 dose of rAHF since study enrollment in the GER study. Results: At the time of analysis, the INT study SAS comprised 707 patients, 156 of whom had received ≥5 years of rAHF treatment during the study. The GER study SAS comprised 382 patients, 231 of whom had received ≥5 years of rAHF treatment. Average Gilbert scores (all joints) were consistently low (years 1-6: median 0-1.0; mean 0-1.3) for both children aged 2 to <12 years and adolescents aged 12 to <18 years receiving rAHF prophylaxis within both studies. In the INT study, average Gilbert scores were lower with prophylaxis than with OD therapy in adults (aged ≥18 years) throughout the observation period (years 1-6: median: 0.9-1.4 [n=8-25] vs 1.4-6.3 [n=2-8], respectively; mean: 1.4-2.2 vs 2.1-6.3; respectively); significant differences (P<0.05) between mean values were observed for years 3, 4, and 6. In the GER study, average Gilbert scores were slightly higher with prophylaxis than with OD in adults (years 1-6: median: 0.7-2.2 [n=12-37] vs 0.3-1.4 [n=2-15], respectively; mean: 1.0-2.7 vs 0.5-2.2, respectively; P-values not available). In the INT study, ABRs were consistently lower in patients receiving rAHF prophylaxis than in those receiving rAHF OD, irrespective of disease severity (Table). A similar trend was observed in the GER study in patients with severe HA, whereas ABRs were similar for both treatment regimens in patients with moderate HA. In both studies, greater proportions of patients with moderate or severe HA receiving rAHF prophylaxis had 0 bleeds than those receiving rAHF OD (Table). In the INT study, 842 AEs were reported in 116/156 (74.4%) patients, including 2 treatment-related serious AEs in 2 (1.3%) patients. In the GER study, 1321 AEs were reported in 197/231 (85.3%) patients, including 29 treatment-related serious AEs in 14 (6.1%) patients. Conclusions: These findings in patients receiving rAHF for ≥5 years in a real-world setting corroborate previous data on the long-term efficacy and tolerability of rAHF in patients with moderate or severe HA. rAHF demonstrated effectiveness in maintaining joint health (as measured by Gilbert scores) in adult patients. Table Disclosures Tsakiris: Roche: Research Funding; Shire, a Takeda company: Research Funding; Sobi: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding. Oldenburg:Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Klamroth:Pfizer: Consultancy, Research Funding, Speakers Bureau; Biotest: Speakers Bureau; Grifols: Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau. Guillet:CSL Behring: Research Funding, Speakers Bureau; Octapharma: Research Funding; Bayer: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Speakers Bureau; Roche-Chugai: Consultancy, Speakers Bureau. Khair:Shire, a Takeda company: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Baxalta/Shire, Takeda companies: Research Funding. Huth-Kühne:Bayer: Consultancy; CSL Behring: Consultancy; Shire, a Takeda company: Consultancy; Sobi: Consultancy. Kurnik:Sobi: Consultancy, Research Funding; Biotest: Consultancy, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Pfizer: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau. Regensburger:Takeda Pharma Vertrieb GmbH & Co. KG: Current Employment, Current equity holder in publicly-traded company. Botha:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Fernandez:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Tang:Takeda Pharmaceutical International AG: Current Employment, Current equity holder in publicly-traded company. Ozelo:Pfizer: Consultancy, Research Funding; Shire/Takeda: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Bioverativ/Sanofi: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau.

scholarly journals Realmind: A Prospective, Multicenter, Observational Study of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Starting Second- or Third-Line Therapy and Not Receiving Autologous Stem Cell Transplant

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5010-5010
Author(s):  
Christopher R. Flowers ◽  
John M. Burke ◽  
Mirko Vukcevic ◽  
Susan Snodgrass ◽  
Shreekant Parasuraman ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Initial Diagnosis ◽  
Cell Transplant ◽  
Publicly Traded ◽  
Line Therapy ◽  
Patient Reported ◽  
The Us ◽  
Third Line

Abstract Background While >60% of patients with diffuse large B-cell lymphoma (DLBCL) are cured when treated with R-CHOP after initial diagnosis, ~40% will be refractory or relapse (R/R) after achieving a response with first-line therapy. Until recently, patients with R/R disease have been treated with rituximab + chemotherapy combinations, rituximab + lenalidomide and salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT). Additional FDA-approved treatment options, recently introduced, include the CD19-directed cytolytic antibody tafasitamab in combination with lenalidomide (granted accelerated approval) for second-line or later patients, as well as CAR T-cell therapies, the CD79b-directed antibody-drug conjugate polatuzumab combined with bendamustine + rituximab, and the CD19-directed antibody-drug conjugate loncastuximab for third-line or later patients. Sequencing these various options and identifying the optimal choice of treatment for individual patients can be challenging for practicing oncologists. The realMIND study (NCT04981795), will assess treatment patterns, physician-reported clinical outcomes and patient-reported health-related quality of life (HRQoL) among patients with R/R DLBCL not eligible for ASCT, and is designed to produce data to support physician decision-making in individualized, patient-centric care. realMIND also has a special focus on patients belonging to racial and ethnic minority groups, different age groups, and those with different socio-economic statuses to ensure strong representation among the US patient population. Study design and methods realMIND is a Phase IV, multicenter, prospective, observational study in which an estimated 1,000 patients will be enrolled from ~75 sites in the US. Enrollment will aim to achieve a representative distribution of adult patients by age, gender, race and ethnicity by actively seeking sites from a broad range of locations, including otherwise under-represented populations. Eligible patients will be aged ≥18 years with histologically confirmed DLBCL at initial diagnosis (including high-grade double- and triple-hit lymphoma), and R/R status after at least one prior systemic therapy and prior to second- or third-line therapy for DLBCL (Figure 1). Patients currently receiving ASCT (but not those with prior ASCT experience) will be excluded. Physician-validated clinical outcomes will include complete response rate, overall response rate, duration of response, event-free survival and overall survival. Safety will be evaluated by assessing serious adverse events (AEs) and AEs leading to treatment discontinuation, interruption or dose modification, as well as AEs in patients treated with tafasitamab. Pathology assessments such as biomarker status (e.g. antigen expression on tumor cells) will be identified using clinical samples taken at initial diagnosis and relapse. Patient-reported outcomes will include general and lymphoma-specific measures of HRQoL (EORTC QLQ-C30 and FACT-Lym), collected as part of usual care visits at least quarterly during follow-up. The end of the study is expected to occur approximately 79 months after the first patient is enrolled to ensure a minimum of 24 months' follow-up after last patient enrollment. The distribution of patient characteristics and all survival outcome measures will be presented using descriptive statistics; time-to-event analyses will be conducted using Kaplan-Meier methods. Summary realMIND is a large-scale, multicenter, real-world study that aims to describe the treatment patterns and clinical outcomes of patients with R/R DLBCL. The study is currently enrolling with a planned sample size of 1,000 patients from ~75 sites in the US. The study population will aim to enroll a representative distribution of patients within the US, facilitating an investigation of outcomes in a patient population reflecting real-world clinical practice. Funding: MorphoSys AG. Figure 1 Figure 1. Disclosures Flowers: National Cancer Institute: Research Funding; BeiGene: Consultancy; Bayer: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Biopharma: Consultancy; Epizyme, Inc.: Consultancy; Denovo: Consultancy; Genmab: Consultancy; Amgen: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech/Roche: Consultancy, Research Funding; Sanofi: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; Ziopharm: Research Funding; Pharmacyclics/Janssen: Consultancy; SeaGen: Consultancy; Xencor: Research Funding; Kite: Research Funding; 4D: Research Funding; Acerta: Research Funding; TG Therapeutics: Research Funding; Pfizer: Research Funding; Spectrum: Consultancy; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Adaptimmune: Research Funding; Allogene: Research Funding; Takeda: Research Funding; Novartis: Research Funding; Nektar: Research Funding; Morphosys: Research Funding; EMD: Research Funding; Janssen: Research Funding; Iovance: Research Funding; Guardant: Research Funding; Cellectis: Research Funding; Pharmacyclics: Research Funding. Burke: Kura: Consultancy; MorphoSys: Consultancy; AbbVie: Consultancy; Roche/Genentech: Consultancy; Verastem: Consultancy; Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy; Kymera: Consultancy; X4 Pharmaceuticals: Consultancy; Beigene: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy; SeaGen: Consultancy, Speakers Bureau; Epizyme: Consultancy. Vukcevic: MorphoSys: Current Employment. Snodgrass: Incyte Corporation: Current Employment. Parasuraman: Incyte Corporation: Current Employment, Current equity holder in publicly-traded company, Other: Support for attending meetings and/or travel. Büchele: MorphoSys: Current Employment, Current equity holder in publicly-traded company. Kurukulasuriya: MorphoSys: Current Employment, Current equity holder in publicly-traded company, Other: Support for attending meetings/travel.

scholarly journals Cardiovascular (CV)-Related Hospitalizations and Associated Costs Among US Patients in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) in Routine Clinical Practice

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4151-4151
Author(s):  
Stuart L. Goldberg ◽  
Michael J. Mauro ◽  
Jorge E. Cortes ◽  
Scott Justin Keating ◽  
Hitesh Bhandari ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Hospital Stay ◽  
Cardiac Failure ◽  
Research Funding ◽  
The United States ◽  
Routine Clinical Practice ◽  
Categorical Variables ◽  
The Us ◽  
Equity Ownership

Introduction: CV events in CP-CML can negatively impact clinical and survival outcomes (Coutinho et al, Clin Lymphoma Myeloma Leuk, 2017), and CV-related hospitalization (hosp.) is costly (Nicholson et al, Clinicoecon Outcomes Res, 2016; Naccarelli et al, Clin. Cardiol, 2010). Mounting evidence suggests the common CV risk factors observed in individuals over the age of 60 combined with tyrosine kinase inhibitor (TKI) therapy may contribute to CV events in patients (pts) with CP-CML (Moslehi & Deininger, J Clin Oncol, 2015; Aghel et al, Vasc Health Risk Manag, 2017). SIMPLICITY is an ongoing observational study of pts with CP-CML receiving first-line (1L) TKIs in routine clinical practice in Europe and the United States (US). Here, we assess CV-related hosp. rates for SIMPLICITY pts in the US receiving 1L imatinib (IM), dasatinib (DAS), or nilotinib (NIL), including the incidence of hospital admissions and length of hospital stay (LOS), and related costs. Methods: In US pts, CV-related hosp. during 1L IM, DAS, or NIL therapy were identified from review of the electronic case report forms completed by clinicians. To control for possible confounding effects of multiple lines of TKI therapy, pts were followed from 1L TKI initiation to 30-days post-treatment or TKI switch, whichever came first. CV-related hosp. rates and LOS during 1L therapy were evaluated on a per-1,000-pt-year (PY) basis. For each CV event, mean total hosp. costs were derived from the 2016 Healthcare Cost and Utilization Project-National (Nationwide) Inpatient Sample database, to which professional fees from peer-reviewed literature were added; the medical component of the Consumer Price Index was used to convert 2016 costs to 2018 US dollars ($). Statistical comparisons for continuous variables were made using t-tests and the Mann-Whitney U test, and chi-square test for categorical variables. Time to first CV-related hosp. was evaluated using Kaplan-Meier methods with the log-rank test. Results: In the US, 808 pts were receiving 1L IM (n=243), DAS (n=301), or NIL (n=264); median follow-up was approximately 4 years (48.7-51.3 months). Age, treatment center type, and baseline fatigue differed significantly between the groups (p<0.05); stratification of duration of therapy in pts showed significant differences between the three TKI cohorts (p=0.0005; Table 1). The number of pts with CV-related hosp. was similar between IM (11 [4.5%]) and DAS (13 [4.3%]) cohorts, but higher in the NIL cohort (21 [8.0%]), equating to 16.6, 14.1, and 25.0 CV-related hosp. per 1,000 PY, respectively. Total CV-related LOS was 81, 36, and 98 days for the IM, DAS, and NIL groups, respectively, translating to 122.4, 46.5, and 116.9 hospital stay days per 1,000 PY. Most frequently experienced CV events were cardiac failure (IM=3.0, DAS=3.2, NIL=7.2 [per 1,000 PY]) and hemorrhage (IM=7.6, DAS=2.2, NIL=4.8 [per 1,000 PY]); rate of the latter was lowest in the DAS group. The rate of myocardial infarction-related hosp. was 1.5 and 2.4 per 1,000 PY for IM and NIL cohorts, respectively. Most inpatient days were due to cardiac failure (IM=13.6, DAS=10.8, NIL=56.1 [per 1,000 PY]) and hemorrhage (IM=80.1, DAS=5.4, NIL=22.7 [per 1,000 PY]); for DAS and NIL, cardiac failure caused the most inpatient days, whereas CV-related hemorrhage was responsible for the most IM-related hospitalization days. 43.8% of the observed CV-related hosp. occurred within 12 months of 1L TKI initiation, with 68.8% occurring by the 18-month mark (Figure 1). No difference in time to first CV-related hosp. with 1L TKI was seen between cohorts (p=0.4644). CV-related hosp. costs were highest among pts receiving IM or NIL, approximately twice that of the DAS cohort. Estimates derived from the product of mean hosp. cost per CV event and the rate of hosp. showed total CV hosp. costs of $475,058, $264,053, and $495,688 per 1,000 PY for IM, DAS, and NIL, respectively. Conclusions: CV-related events and hosp. were reported among US pts with CP-CML receiving 1L TKIs; the majority of which occurred within 18 months of TKI initiation. The incidence of CV-related hosp. and LOS, and mean hosp. costs were lowest among pts receiving DAS compared with the IM and NIL cohorts. The potential for added morbidity, healthcare utilization, and associated costs due to CV complications must be considered when making decisions on the appropriate TKI for individual pts with CP-CML. Disclosures Goldberg: Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership; Bristol-Myers Squibb: Consultancy; COTA: Equity Ownership. Mauro:Bristol-Myers Squibb: Consultancy; Novartis Oncology: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; BiolineRx: Consultancy; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Keating:Bristol-Myers Squibb: Employment. Bhandari:SmartAnalyst India (Pvt.) Ltd.: Employment, Other: I am an employee of SmartAnalyst India (Pvt.) Ltd., a subsidiary of SmartAnalyst Inc. which was contracted by Bristol-Myers Squibb for carrying out this analysis. Chen:Bristol-Myers Squibb: Employment.

Perceptions of Patient Disease Burden and Management Approaches of Systemic Mastocytosis (SM) By Healthcare Providers: Results from the TouchStone SM Survey

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Ruben A. Mesa ◽  
Erin M. Sullivan ◽  
David Dubinsky ◽  
Brittany Carroll ◽  
Valerie M. Slee ◽  
...  
Keyword(s):  
Disease Management ◽  
Symptom Onset ◽  
Research Funding ◽  
Healthcare Providers ◽  
Diagnostic Tools ◽  
Treatment Goals ◽  
Publicly Traded ◽  
Similar Treatment ◽  
The Us ◽  
Kit D816v

Introduction: SM is a rare, mast cell neoplasm characterized by uncontrolled proliferation, accumulation, and activation of abnormal mast cells (MCs). Approximately 95% of patients with SM harbor the D816V mutation, which results in constitutive activation of the KIT receptor, causing debilitating symptoms across all SM subtypes such as pruritus, headaches, bone pain, nausea, vomiting, diarrhea, brain fog, and anaphylaxis. Patients with SM are managed across specialties depending on symptom severity and organ involvement. Hematologists/oncologists and allergists/immunologists both play key roles in the management of disease. With few multidisciplinary SM practices in the US, more information is needed across specialties to enable optimal SM care. Here we report findings from the TouchStone SM survey of healthcare providers (HCPs) in the US to inform perceptions of disease and disease management strategies. Methods: HCPs completed an online survey containing 47 items covering a range of concepts related to diagnosis (how made, how long it takes), symptoms (how assessed, what symptoms patients experience, how HCPs discuss symptoms with patients, treatment and management), perceived impact on daily life, treatment received (prescription and over-the-counter, treatment goals, unmet needs) and satisfaction (symptom management, overall treatment and disease management). The focus of these analyses are HCP perceptions of disease severity, treatment goals, and disease management. Practicing hematologists/oncologists and allergists/immunologists were eligible if caring for ≥4 SM patients and in practice ≥3 years post fellowship. HCPs were recruited through double-blinded market research survey panels, with individual responses kept confidential. Descriptive analyses were performed on survey responses. Results: Of 304 HCPs contacted, 60 allergists/immunologists and 59 hematologists/oncologists were enrolled with an average of 14 years of practice experience. On average, participating HCPs had 25 SM patients (range: 4-100) under their care. HCPs reported perceived prevalence of the KIT D816V mutation at 46% of patients (range 0-100), substantially lower than published prevalence rates of up to 95%.1 Among HCPs, the average perceived time from patient symptom onset to diagnosis was 8 months, in contrast to 7 years as reported by patients.2 Allergist/immunologists reported primarily seeing patients with non-advanced disease (80%), while hematologists/oncologists reported managing both non-advanced (50%) and advanced patients (50%). Participating HCPs reported that 58% of their patients have moderate-severe SM. HCP treatment goals for SM patients were consistent across specialties. The 2 most important treatment goals for non-advanced patients were improved quality of life (QoL) (40%; 48/120) and improvement of symptoms (24%; 29/119), while the 2 most important treatment goals for advanced patients were improved progression-free survival /improved overall survival (34%, 35/104) and improved QoL (25%, 26/104). Conclusions: Allergists/immunologists co-manage SM care with hematologists/oncologists, particularly in non-advanced SM, and have similar treatment goals for this patient population, including improvement in QoL and symptom control. In this sample of HCPs, the perceived prevalence of the KIT D816V mutation as well as the perceived time from symptom onset to diagnosis were substantially lower than published estimates. These gaps identified suggest a need to improve HCP awareness of SM symptoms and diagnostic tools to help facilitate earlier patient diagnosis. 1. Garcia-Montero et al. Blood. 2006;108(7):2366-2372. 2. Jennings SV et al. Immuno Allergy Clin North Am. 2018;38(3):505-525. Disclosures Mesa: Promedior: Research Funding; Incyte: Research Funding; Genetech: Research Funding; CTI: Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Sierra Onc: Consultancy; Novartis: Consultancy; LaJolla Pharma: Consultancy; Samus: Research Funding. Sullivan:Blueprint Medicines Corporation: Current Employment, Current equity holder in publicly-traded company. Dubinsky:Blueprint Medicines Corporation: Current Employment, Current equity holder in publicly-traded company. Carroll:Blueprint Medicines Corporation: Consultancy, Current equity holder in publicly-traded company. Mathias:Blueprint Medicines Corporation: Other: employed by Health Outcomes Solutions, which received funding Blueprint for providing assistance in developing the Touchstone survey. Castells:Blueprint Medicines Corporation: Consultancy, Other: Clinical trials: Principle Investigator; UpToDate: Other: Author fee; Annals of Allergy, Asthma & Immunology: Other: Editorial Board.

scholarly journals Follow-up Analysis of Ixazomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Routine Clinical Practice

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2716-2716
Author(s):  
Jiri Minarik ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
Jan Straub ◽  
Tomas Jelinek ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Previous Analysis ◽  
Progression Free Survival ◽  
Routine Clinical Practice ◽  
Toxicity Profile ◽  
Advisory Committees ◽  
Free Survival ◽  
Significant Difference

Abstract Background: The addition of ixazomib to the doublet lenalidomide and dexamethasone (RD) in relapsed and refractory multiple myeloma (RRMM) has shown significant benefit in progression free survival (PFS) in the TOURMALINE-MM1 study. Several real-world data including our previous analysis confirmed that the combination IRD is feasible and with fair outcomes even outside the clinical trial. Here we report an updated analysis which is aimed at overall survival (OS) and the PFS2 interval which is defined as the time from the date of treatment initiation to the date of first documentation of progressive disease after initiation of further anti-myeloma treatment or death from any cause. Methods: We analyzed a cohort of 344 patients with RRMM, 127 being treated by IRD and 217 by RD combination. The group characteristics and study design are described elsewhere. 1 The median follow-up of the whole cohort was 28.5 months. The primary endpoint was OS, OS in patients with relapse 1-3, progression free survival (PFS), and PFS2. Secondary endpoints were response rates and toxicity profile. For statistical analysis we used Fisher's exact test or Mann-Whitney U test. Survival measures were assessed using the Kaplan-Meier methodology, and statistical significance was assessed using the log-rank test at a significance level of α = 0.05 (all tests two-sided). Results: The outcomes of OS in the whole cohort were already published before, with significantly longer median OS in the IRD vs RD cohort (mOS 36.6 months vs 26.0 months, p = 0.008).1 In the follow-up analysis, the medians were slightly improved, maintaining a significant difference (mOS 40.9 vs 27.1 months, p = 0.001). In patients treated within relapse 1-3, the results outcomes were even more pronounced (mOS 51.7 vs 27.8 months, p ˂ 0.001). The median PFS was also better in the IRD cohort (mPFS 17.5 vs 12.5 months, p = 0.013) but the results did not substantially differ from our previous analysis. The median PFS2 in the IRD vs RD cohort was significantly longer in the IRD cohort (mPFS2 29.8 vs 21.6 months, p = 0.016). The subsequent therapy included mostly pomalidomide (27.5% vs 30.8%), bortezomib (28.8% vs 28.2%) or thalidomide (10.0% vs 16.2%). Monoclonal antibodies (daratumumab, isatuximab) were more frequently used after IRD combination (21.3% vs 4.3%). The response rates in the IRD vs RD cohort were similar as in our primary analysis: overall response rate (ORR) 73.0% vs 66.8%, with significant difference in very good partial response and better (VGPR+) 38.1% vs 26.3%. The toxicity profile did not reveal any additional safety concerns. Majority of grade 3+ toxicities included hematological toxicity (anemia, neutropenia, thrombocytopenia) and infections, with similar distribution in the cohorts. Conclusion: The treatment of RRMM using the full oral IRD regimen in routine clinical practice is easy, safe and with significantly improved outcomes in comparison to RD doublet. Our follow-up analysis confirmed the impact on OS in patients in the whole cohort including relapse 1-3. The median PFS2 was also longer in the IRD cohort, possibly affected by more frequent use of monoclonal antibodies in the next treatment. With support of AZV 17-29343A, NV18-03-00500, MH CZ - DRO (FNOl, 00098892), IGA-LF-2021-001. 1) Minarik J, Pika T, Radocha J. et al. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. BMC Cancer 2021; 21: https://doi.org/10.1186/s12885-020-07732-1 Disclosures Minarik: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Hajek: Novartis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Pharma MAR: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Safety and Antitumor Activity Study Evaluating Loncastuximab Tesirine and Rituximab Versus Immunochemotherapy in Diffuse Large B-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Yuliya Linhares ◽  
Mitul D Gandhi ◽  
Michael Chung ◽  
Jennifer Adeleye ◽  
David Ungar ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Advisory Board ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Introduction: Patients with diffuse large B-cell lymphoma (DLBCL) who fail immunochemotherapy (IC) and are unsuitable for autologous stem cell transplantation (ASCT) and those who relapse shortly after ASCT have extremely poor prognosis and need additional treatment options. Loncastuximab tesirine (Lonca) is an antibody-drug conjugate (ADC) composed of a humanized anti-CD19 antibody conjugated to a pyrrolobenzodiazepine dimer toxin. In a Phase 2 study (NCT03589469), Lonca demonstrated single-agent antitumor activity with manageable toxicity in patients with relapsed/refractory (R/R) DLBCL. Rituximab is a CD20-targeting monoclonal antibody used in front-line IC for DLBCL and in salvage regimens, such as rituximab/gemcitabine/oxaliplatin (R-GemOx). The addition of rituximab to a CD19-targeting pyrrolobenzodiazepine ADC appears to prolong tumor control in preclinical studies, providing the rationale for evaluating Lonca combined with rituximab (Lonca-R) as a treatment for R/R DLBCL. Study Design and Methods: This is a Phase 3, randomized, open-label, 2-part, 2-arm, multicenter study of Lonca-R versus standard IC in patients with R/R DLBCL (NCT04384484). Part 1 is a nonrandomized safety run-in with Lonca-R. The toxicity of Lonca-R will be compared with previous single-agent Lonca safety data after 20 patients have completed Cycle 1 in Part 1. Provided no significant increase in toxicity is observed, Part 2 will be initiated. Part 2 is a randomized study of Lonca-R versus R-GemOx (Figure 1). Key inclusion and exclusion criteria are reported in Table 1. The primary objective of Part 2 is to evaluate the efficacy of Lonca-R versus R-GemOx, using progression-free survival (PFS) as the primary endpoint. PFS will be defined as the time between randomization and first documentation of recurrence, disease progression or death (central review) and the primary analysis will compare PFS between treatment arms using stratified log-rank testing. Secondary objectives include evaluation of safety, pharmacokinetics, and immunogenicity of the combination, in addition to the impact of treatment on symptoms, patient-reported outcomes and patients' overall health. In Part 1 and in the Lonca-R arm of Part 2, patients will receive intravenous (iv) Lonca at 150 µg/kg on day 1 of each 21-day cycle for 2 cycles, then at 75 µg/kg on day 1 for up to 6 additional cycles. Rituximab 375 mg/m2 iv will be administered subsequent to Lonca infusion on day 1 of each cycle. Patients treated with Lonca-R will also be given dexamethasone 4 mg (oral, twice a day), where not contraindicated, on the day before, the day of, and the day after Lonca-R infusion. In the R-GemOx arm, patients will receive rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatin 100 mg/m2 iv on day 1 of each 14-day cycle up to a total of 8 cycles. Patients will receive premedication and supportive care according to the respective prescribing information for rituximab, gemcitabine, and oxaliplatin. The trial is planned to open in Q3/Q4 2020, and target enrollment is 350 patients. Funding: This study is sponsored by ADC Therapeutics SA; https://clinicaltrials.gov/ct2/show/NCT04384484. Disclosures Linhares: Jazz Pharmaceuticals: Consultancy; ADC Therapeutics, Verastem Oncology, Bristol Myers-Squibb (Juno), AstraZeneca: Research Funding; Miami Cancer Institute, Baptist Health South Florida: Current Employment. Gandhi:TG Therapeutics (Advisory board), GlaxoSmithKline (Advisory board): Membership on an entity's Board of Directors or advisory committees. Adeleye:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Ungar:ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Hamadani:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme, AstraZeneca: Speakers Bureau; Janssen R&D; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio: Consultancy; Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma: Research Funding. OffLabel Disclosure: Rituximab is licensed for treatment of NHL but is being used in combination with an unlicensed drug (loncastuximab tesirine) in this study

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