scholarly journals Clinical & Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice in Israel

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 23-24
Author(s):  
Martin H. Ellis ◽  
Tamar Tadmor ◽  
Gabriel Chodick ◽  
Naama Yekutiel ◽  
Moti Levi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Polycythemia Vera ◽  
Board Of Directors ◽  
Routine Clinical Practice ◽  
Institutional Research ◽  
Advisory Committees ◽  
Economic Implications ◽  
A Company ◽  
Research Grant

Background: Hydroxyurea (HU) is an effective and common therapy for high-risk Polycythemia Vera (PV). Some patients may demonstrate resistance or intolerance to HU, but the consequences of these warrant further studies. Objective: Evaluate the clinical and economic implications of HU resistance/intolerance, in routine clinical practice in Israel. Methods: A retrospective analysis of Maccabi Health Services' (MHS) database was performed. MHS is a Non-for-Profit healthcare insurer and provider in Israel, with over 2.2 million members. Patients were included in the study if they had a recorded PV diagnosis or complete blood count indicative of PV, and had purchased HU for at least 3 months between 2000-2015. Enrolled patients were divided into 3 groups: A) Resistant to HU (patients prescribed 2g/day of HU); B) Intolerant of HU (patients who stopped HU, transitioned to another line of therapy or who developed HU related cytopenias); C) Stable on HU. A mid-time point was added to "Stable" to compensate for the time required for transition in the "Intolerant" group. Only patients who developed Intolerance within 5 years were included. Collected data pertained to demographics, clinical outcomes, resource utilization and expenditure data. Results: A total of 830 patients were identified. Only 3 met criteria for Resistance and were disregarded for further analysis, while 318 (38%) were defined as "Intolerant" and 509 (61%) as "Stable". At baseline, there were no significant differences between "Intolerant" and "Stable" groups, apart from platelet counts (431 vs. 495, respectively) and red cell distribution width (RDW) (18.4 vs. 17.6, respectively). Intolerance was determined based on HU-related cytopenias (n=144, 45% of Intolerant), transition to other treatment line (n=52, 16%) or stopping HU (n=122, 38%). These results indicate some patients continue HU treatment despite lack of disease control. "Intolerant" patients who had transitioned by 5 years from first HU purchase (N=173) and "Stable" patients who met the mid-point of time to transition (N=487) were eligible for comparison. Median follow up time was 4.9 and 5.5 years for "Intolerant" and "Stable" groups, respectively. Thrombotic events occurred in 8% of the "Intolerant" group compared with 3% of "Stable" (p=0.003) and event rate per 100 patient-years was 1.6 versus 0.5 (p<0.001). Progression to MF occurred in 28% versus 5% (p<0.001), and progression to AML occurred in 6% compared with 1% (p<0.001) among "Intolerant" and "Stable", respectively. Interestingly no significant difference was found regarding major arterial thrombotic complications, (myocardial infarction, acute coronary syndrome, cerebrovascular accident or limb ischemia). During study follow up, hospitalization occurred in 84% versus 69% (p<0.001), and hospitalization days were 5.3 vs 1.9 per year (p=0.004) among "Intolerant" and "Stable" groups, respectively. Death occurred in 58% of "Intolerant" compared with 30% of "Stable"(p<0.001). Treatment costs for an Intolerant patient in the first year after intolerance were 2.6-fold higher than those for a Stable patient, driven mainly by hospitalization costs being 3.6-fold higher (data available from 2010). Conclusions: The results of this analysis indicate that intolerance to HU treatment in PV patients is associated with serious clinical and economic implications, indicating a need for improved treatment for these patients. Disclosures Ellis: Novartis Pharma AG: Consultancy, Honoraria, Other: Institutional research grant; BMS: Consultancy, Other: Institutional research grant; Gilead: Other: Institutional research grant. 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. Chodick:Novartis Pharma AG: Other: Institutional grant. Yekutiel:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Other: Institutional grant. Sharf:Novartis Pharma AG: Consultancy, Other: Institutional Grant; Leukaemia Patient Advocates Foundation: Ended employment in the past 24 months, Membership on an entity's Board of Directors or advisory committees; Israeli CML Patient Organisation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Other: Institutional grant; AbbVie: Consultancy, Other: Institutional Grant; Amgen: Consultancy, Other: Institutional grant; Bristol Mayers Squibb: Consultancy, Other: Institutional Grant; Celgene: Consultancy, Other: Institutional Grant; AOP Orphan: Other: Institutional grant; CTI: Other: Institutional grant; Medison: Other; Roche: Other; Jansseb: Other; Pfizer: Consultancy, Other; Takeda: Other; Gilead: Other. Feine:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Leef:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Ben Zvi:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Shavit:6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment.

scholarly journals Overview of French Routine Clinical Practice for the Management of Chemotherapy-Induced Anemia (CIA) with Biosimilar Epoetin Alfa in 563 Patients with Lymphoid Malignancies: A National Observational Study (The OncoBOS study)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3342-3342
Author(s):  
Lionel Karlin ◽  
Jean-Philippe Metges ◽  
Nataliya Khobta ◽  
Gilles Boschetti ◽  
Alain Toledano ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Board Of Directors ◽  
Treatment Period ◽  
Blood Cells ◽  
Cell Lymphoma ◽  
Routine Clinical Practice ◽  
Advisory Committees ◽  
Lymphoid Malignancies

Abstract Background. OncoBOS is a prospective, non-interventional study conducted in France to describe modalities of treatment with Binocrit® in routine clinical practice setting, for the correction of hemoglobin (Hb) in patients with CIA receiving chemotherapy (CT) for solid tumors, lymphoma or myeloma. This analysis focuses on patients with lymphoid malignancies (LM). Patients & methods. Patient ≥18 years old with LM, CIA and eligible for treatment with Binocrit® were included. This analysis reports patients characteristics along with anemia-related data such as Hb outcomes, Binocrit® treatment characteristics and concomitant treatments received, at baseline, 3-4 weeks and 12 (± 1) weeks later. Factors associated with a Hb increase ≥2 g/dL in patients with LM were analyzed by means of univariate and multivariate analyses. Results. 563 evaluable patients (302 males (53.6%), mean age 67.9 (SD 14.0) years were recruited from 34 sites, between September 2011 and July 2014. Non-Hodgkin lymphoma (NHL) (281 patients; 49.9%) and multiple myeloma (165 patients; 29.3%) were most prevalent. Among patients with NHL, 46.0% had a diffuse large B cell lymphoma, 11.5% a follicular lymphoma and 11.1% a mantle cell lymphoma. 62.5% of patients with NHL had a stage IV disease and bone marrow was involved by NHL in 45.2% of patients. A vast majority of patients (84.3%) suffering from multiple myeloma had a Durie-Salmon stage III myeloma. Mean baseline Hb was 9.5 (SD 1.0) g/dL, which increased by an average of 0.9 (SD 1.4) g/dL and 1.9 (SD 1.7) g/dL after 1 and 3 months, respectively. A Hb increase ≥1 g/dL was achieved by 51.3% of patients after 3-4 weeks of treatment with Binocrit®. About half of patients (53.0%) achieved a Hb increase ≥2 g/dL at week 12 (± 1). Patients received a mean Binocrit® dose of 31252.4 ± (SD 5815.9; median: 30000) UI once-weekly, over an average time span of 10.8 (SD 3.2; median: 13) weeks. Iron status (serum ferritin and transferrin saturation coefficient) was assessed in 29.1% of subjects at baseline. In total, 2.8% and 1.4% of patients concomitantly received oral or intravenous iron, respectively, during the follow-up period. 12.1% and 11.6% of patients received a folate supplementation at week 3-4 and 12, respectively. Moreover, 16.2% and 15.0% of patients received red blood cells transfusion over the 3-4 first weeks, and over the next 2 months, respectively. Over the treatment period, no treatment‐related adverse reaction was recorded. Factors negatively/positively associated with a Hb increase ≥2 g/dL (p<0.05) in the multivariate analysis were: prior radiotherapy [HR 0.16 (CI95% 0.04;0.64)]; history of venous thrombotic disease [HR 1.93 (1.14;3.28)]; administration of folate during the follow-up [HR 2.43 (1.69;3.49)]; a Hb level < 8 or [8;10[ g/dL at inclusion [HR 3.04 (1.97;4.69) and HR 1.62 (1.25;2.11), respectively]; 2 units of red blood cells received over the treatment period [HR 2.82 (1.91;4.16)]. Conclusions. This study indicates that in real-life clinical conditions Binocrit® increases effectively Hb, without any adverse drug reaction, in anemic patients with lymphoid malignancies, whatever chemotherapy received. The effect of treatment with Binocrit® is rapid, with mean hemoglobin increase of 0.9 (SD1.4) g/dL seen as early as 3 or 4 weeks following the start of therapy. Disclosures Karlin: Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. Metges:Sandoz: Consultancy. Khobta:Sandoz: Membership on an entity's Board of Directors or advisory committees. Boschetti:Sandoz: Membership on an entity's Board of Directors or advisory committees. Toledano:Sandoz: Membership on an entity's Board of Directors or advisory committees. Aubron-Olivier:Sandoz: Employment. Fernet:Sandoz: Employment. Fitoussi:Sandoz: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Minimal Residual Disease Eradication with Venetoclax in Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-14
Author(s):  
Alexander Coltoff ◽  
Joseph G. Jurcic ◽  
Peter Campbell ◽  
Daniel J. Lee ◽  
Mark L Heaney ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Institutional Research ◽  
Negative Group ◽  
Advisory Committees ◽  
Research Grants

Introduction The combination of the BCL-2 inhibitor venetoclax with an HMA (HMA/Ven) has improved outcomes in previously untreated patients with AML not eligible for intensive induction therapy. In a phase Ib study, 67% of patients achieved a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) with a median overall survival (OS) of 17.5 months (DiNardo CD et al. Blood 2019; 133(1):7-17). HMA/Ven has also demonstrated efficacy in a heavily pretreated population with relapsed or refractory (R/R) AML, the majority of whom had prior HMA exposure (DiNardo CD et al. Am J Hematol 2018; 93(3):401-7). Measurable residual disease (MRD) is recognized as an independent prognostic indicator important for risk stratification and treatment planning (Schuurhuis GJ et al. Blood 2018; 131(12):1275-91). To date, however, there have been few reports on the effect of HMA/Ven on MRD. Methods This is a retrospective case series of patients with AML at a single-center tertiary-care institution. Patients ≥ 18 years of age who were treated with HMA/Ven between January 2017 and June 2020, either in the upfront or salvage setting, for AML were included. Outcomes included CR/CRi rate, MRD response, relapse free survival (RFS), and OS. MRD was assessed via multicolor flow cytometry with a sensitivity of 10-3 (0.1%). Results Nineteen patients were identified, 12 (63%) of whom were female. The median age at the time of HMA/Ven initiation was 71 years (range, 21 - 87 years). Ten (53%) patients had de novo AML and 9 had secondary or therapy-related AML. By 2017 ELN criteria, 3 (16%) patients had favorable-risk, 9 (47%) had intermediate-risk, and 7 (37%) had adverse-risk AML. Nine (47%) patients had R/R AML; 5 received HMA/Ven as first salvage therapy, and 4 as 2nd or greater salvage. Three (16%) patients had prior HMA exposure. No patient had prior venetoclax exposure. Median follow-up was 9.1 months (range, 1-21.1 months). Ten (53%) patients received azacitidine and 9 (47%) were given decitabine. Venetoclax doses ranged from 50 to 400 mg daily, depending on participation in a clinical trial and concomitant medications. Eight patients achieved a CR and 7 patients achieved a CRi for a combined CR/CRi rate of 79%. The CR/CRi rate was 90% (9/10) in the upfront setting, and 66% (6/9) in the salvage setting. The median time and number of cycles to best clinical response was 2.3 months (range, 0.9-3.9 months) and 2 (range, 1-3 cycles), respectively. Eleven (73%) of the 15 responders achieved MRD clearance after a median of 2 cycles (range, 1-3 cycles) (Table 1). Two of 4 (50%) MRD-positive patients relapsed, while 4 (36%) of 11 MRD-negative patients relapsed (Figure 1). Relapse occurred at a median of 2.0 months (range, 1.3-2.7 months) in the MRD positive group and 11.0 months (range, 2.8-14 months) in the MRD negative group. One patient died of infectious complications while MRD negative. Three patients, all of whom were treated for R/R disease, proceeded to an allogeneic stem cell transplant (HSCT). Two were MRD negative at the time of HSCT and all remained in remission. At the time of data cutoff, 7 (64%) of 11 MRD-negative patients were alive, and all 4 MRD-positive patients were alive. Causes of death in the MRD-negative group included disease relapse (3 patients) and infection (1 patient). Median overall survival in the entire cohort (range, 32 days-NR) was not reached. Conclusions HMA/Ven was highly effective as both upfront and salvage therapy. Surprisingly, the salvage CR/CRi rate in this series was 66%, allowing half of the responders to proceed to HSCT. The majority (73%) of responders achieved MRD negativity. While MRD status influenced RFS, 36% of MRD-negative patients relapsed. Additionally, the same percentage of MRD-negative patients died during follow-up, versus none of the patients with MRD-positivity. This indicates the need for more sensitive methods to assess MRD and for novel therapeutic strategies to eliminate MRD, thereby improving long-term outcomes. Larger prospective studies are needed to define the role of MRD assessment with venetoclax-containing regimens. Disclosures Jurcic: AbbVie:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Syros Pharmaceuticals:Research Funding;PTC Therapeutics:Research Funding;Arog Pharmaceuticals:Research Funding;Kura Oncology:Research Funding;Forma Therapeutics:Research Funding;Astellas:Research Funding;Genentech:Research Funding;Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS:Consultancy, Research Funding.Campbell:AstraZeneca:Consultancy.Lee:Genentech:Research Funding;Sumitomo Dainippon Pharma Oncology, Inc.:Research Funding;AbbVie:Research Funding;Novartis:Research Funding;Bayer:Research Funding;Celgene:Consultancy;Forty Seven:Research Funding.Heaney:Blueprint Medicines Corporation:Research Funding;BMS:Research Funding;CTI Biopharma:Consultancy, Research Funding;Deciphera:Research Funding;Incyte:Research Funding;Novartis:Consultancy, Research Funding;Sierra Oncology:Research Funding;AbbVie:Consultancy;Partner Therapeutics:Consultancy.Lamanna:Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Octapharma:Research Funding;Juno:Other: Institutional research grants, Research Funding;Gilead:Consultancy, Membership on an entity's Board of Directors or advisory committees;Astra Zeneca:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Pharmacyclics:Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Bei-Gene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Abbvie:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Oncternal, Verastem, TG Therapeutics:Other: Institutional research grants, Research Funding;MingSight:Other: Institutional research grants, Research Funding;Loxo:Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees;Columbia University Medical Center:Current Employment.

scholarly journals Weight Loss Predicts Inferior Outcome in Polycythemia Vera Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Albert Jang ◽  
Hussein Hamad ◽  
Sarvari Venkata Yellapragada ◽  
Iberia R. Sosa ◽  
Gustavo A. Rivero
Keyword(s):  
Weight Loss ◽  
High Risk ◽  
Blood Cell ◽  
Polycythemia Vera ◽  
Board Of Directors ◽  
Clinical Variable ◽  
Advisory Committees ◽  
Wbc Count

Background: Conventional risk factors for inferior outcomes in polycythemia vera (PV) include elevated hematocrit, white blood cell (WBC) count, age, and abnormal karyotype. Weight loss adversely impacts survival in cancer patients. JAK2 myeloproliferative neoplasms (MPN) upregulate tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8 and induce decreased leptin levels leading to weight loss. The impact of weight loss in PV patients receiving best supportive care (i.e. frontline hydroxyurea [HU] therapy, phlebotomy) on overall survival (OS) is largely unknown. In this study, we seek to investigate: (1) differential effect on survival for weight loss, and (2) variables with predictive value for weight loss among JAK2 inhibitor-naïve PV patients. Methods: After IRB approval, 46 patients at the Michael E. DeBakey VA Medical Center diagnosed with PV between 2000 and 2016 were selected for analysis. Our outcome of interest was OS among PV patients exhibiting weight loss versus patients who maintained, gained weight or had minor weight loss. To objectively estimate weight changes overtime, the difference between baseline BMI [BMI-B] at the time of diagnosis and BMI at last follow-up (BMI-L) was obtained for each patient. Survival analysis was performed for PV patients exhibiting more than 10% weight loss (&gt;10%) versus all other patients (less than 10% loss, stable and increased weight) (&lt;10%) over time. Kaplan-Meier (KM) method was used to determine OS. Cox regression model was performed to assess independent role of different variables including age, blood cell counts and ferritin level Statistical analysis was performed using SAS software. Results: Median BMI loss was 10% (0.03-36.72%); 33/46 (71.7%) and 13/46 (28.2%) patients developed &lt;10% and &gt;10% BMI loss, respectively. Baseline characteristics are summarized in Table 1. Median BMI at last follow up was 21 for PV patients exhibiting &gt;10% BMI loss and 27.7 for PV patients exhibiting &lt;10% BMI loss (p&lt;0.01). Median age was higher among patients exhibiting &gt;10% BMI loss (68 vs 56 y, respectively, p=0.006). A non-significant clinical trend for higher WBC was observed among patients losing &gt;10% BMI (10.9 vs 7.6 K/uL, p=0.08). Median Hemoglobin (Hb), hematocrit (Hct) and ferritin were intriguingly lower in the &gt;10% loss group at 16 vs 18.3 g/dL (p=0.01), 49.3 vs 54.2% (p=0.04) and 29.8 vs 50.6 ng/mL (p=0.09) respectively, while median RDW was higher at 18 vs 15.1% (p=0.01). OS was 9125 days vs 5364 days, in patients with &lt;10% and &gt;10% BMI loss, respectively (p=0.02, HR=0.20; CI 95% 0.04-0.84) (Figure 1). On multivariate analysis, age (hazard ratio [HR], 1.34; p&lt;0.02) and WBC count (HR, 1.57; p&lt;0.01), were predictive of OS. Conclusions: A subgroup of PV patients exhibit progressive weight loss. Over 10% BMI reduction is associated with decreased survival, suggesting that "early weight loss" is an independent clinical variable that predicts high risk PV. While a larger study is needed to validate this observation, this small study highlights the role of leukocytosis, advanced age and weight loss in PV. Confirmation of the observations reported here could unveil an important role for pharmacologic and/or dietary interventions to improve survival among high-risk PV patients. Disclosures Rivero: agios: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees.

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 EARLY Results of TOTAL Therapy 7 (TT7): High Response Rates of NEWLY Diagnosed High Risk Myeloma to Daratumumab

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4569-4569 ◽  
Author(s):  
Frits van Rhee ◽  
Sharmilan Thanendrarajan ◽  
Carolina D. Schinke ◽  
Jeffery R. Sawyer ◽  
Adam Rosenthal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rates ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Early Results ◽  
Research Grant

Background. The TT approach has significantly improved the outcome of multiple myeloma (MM) by combining new drugs with a regimen that comprises induction, tandem autologous stem cell transplantation (ASCT), consolidation and maintenance. However, a group of 15% of patients with high risk multiple myeloma (HRMM) have derived little benefit despite similar response rates to induction chemotherapy and ASCT when compared to low risk MM. The poor outcome of HRMM is explained by early relapse post ASCT resulting in a short progression free survival (PFS) with only 15-20% of patients surviving long-term. Daratumumab (Dara) is a human IgG1k anti-CD38 monoclonal antibody that has shown favorable results in early single-arm studies and more recently in phase III studies for relapsed/refractory and newly diagnosed MM. In TT7, we introduced Dara during all phases of therapy, including immune consolidation early post ASCT, to improve responses rate and PFS in HRMM. Methods. Patients had newly diagnosed HRMM as defined by high risk cytogenetic abnormalities, presence of extramedullary disease, >3 focal lesions on CT-PET, elevated LDH due to MM, or ISS II/III with cytogenetic abnormality. Dara (16mg/kgx1) was added to induction with KTD-PACE (carfilzomib, thalidomide, dexamethasone; and four-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, etoposide). Conditioning for tandem autologous stem cell transplantation (ASCT) was with fractionated melphalan (50mg/m2x4) (fMEL) based on prior observations that patients with adverse cytogenetics fare better with fMEL rather than single high dose MEL200mg/m2.In the inter tandem ASCT period immunological consolidation with Dara (16mg/kg) alone for 2 doses was followed by Dara (16mg/kg) on day 1 combined with K (36mg/m2) and D (20mg) weekly for 2 cycles. DaraKD was administered to avoid treatment free periods allowing for myeloma regrowth. The 2nd ASCT was followed by further immunological consolidation with Dara (16mg/k) for 2 doses, and maintenance therapy for 3 yrs with 3-months block of alternating Dara-KD (dara 16mg/kg day 1; K 36mg/m2 and dex 20mg weekly) and Dara-lenalidomide (R)D (dara 16mg/kg day 1; R 15mg day 1-21 q28 and D 20mg weekly). Results. TT7 enrolled 43 patients thus far. The median follow-up was 11 months (range: 1-22). The median age was 61 yrs (range 44-73). Sixteen patients were ≥65 yrs (37.2%). A mean of 29.4x106 CD34+ cells/kg (range: 4.6-86.4) were collected. 36 patients completed ASCT #1 (83.7%) and 18 (41.9%) ASCT #2, whilst 14 patients have proceeded to the maintenance phase. R-ISS II/III or metaphase cytogenetic abnormalities were present in 85.1 and 58.1% of patients, respectively. Elevated LDH or >3FL on CT-PET were noted in 30 and 41.8%. The 1-yr cumulative incidence estimates for reaching VGPR and PR were 87 and 83%, respectively. A CR or sCR was achieved in 68 and 46%. The 1-yr estimates of PFS and OS were 91.6 and 87.2%. 40 subjects are alive, whilst 5 progressed on study therapy and 3 subsequently died. 38 patients are progression free at the time of reporting. Dara was well-tolerated and no subjects discontinued therapy due to dara-related side effects. The CR and sCR rates compared favorably to the predecessor HRMM TT5 protocol where CR and sCR rates were 59 and 27%. Conclusion. The early results of TT7 point to increased response rates of HRMM to a dara-based TT regimen with especially higher rates of CR and sCR. Longer follow-up is required to determine if these early results translate into superior PFS and OS. Figure Disclosures van Rhee: Karyopharm Therapeutics: Consultancy; Kite Pharma: Consultancy; Adicet Bio: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy; Castleman Disease Collaborative Network: Consultancy; EUSA: Consultancy. Walker:Celgene: Research Funding. Morgan:Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: research grant, Research Funding. Davies:Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor; Janssen, Celgene: Other: Research Grant, Research Funding.

scholarly journals Solid Tumors in Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Study on 2220 Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3039-3039
Author(s):  
Barbara Mora ◽  
Elisa Rumi ◽  
Paola Guglielmelli ◽  
Daniela Barraco ◽  
Margherita Maffioli ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Board Of Directors ◽  
Solid Tumors ◽  
Essential Thrombocythemia ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Time Dependent ◽  
Jak Inhibitors ◽  
Advisory Committees

Abstract Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) that can progress to post-PV (PPV) myelofibrosis (MF) and post-ET (PET) MF, from now on referred to as secondary myelofibrosis (SMF). Recent studies have shown an increased risk of developing solid tumors (ST) in MPN patients in comparison to the general population. Information on development of ST in SMF is scant. Objectives of this study are to investigate ST in SMF correlating clinical phenotypes and treatments and to evaluate differences in the incidence of ST between PV and ET patients who developed SMF and those who did not. Methods: The SMF group (including only PV and ET who developed SMF) was from the MYSEC cohort with ST-data collected (n=768 SMF); the PV/ET group including only patients who did not evolved into SMF at the time of this analysis was from the Pavia cohort (n=1452, 611 PV and 841 ET). SMF diagnosis was performed according to the IWG-MRT criteria (2008), PV and ET diagnosis was reviewed according to the most recent WHO criteria. We performed time-to-event analysis with Cox regression models using either the time elapsed after ET or PV diagnosis or the time elapsed after SMF diagnosis, events being defined as the diagnosis of ST. Concomitant JAK inhibitor therapy was considered a dynamic (time-dependent) covariate present from the date of drug start. Likewise, the pre- and post-SMF periods were compared considering SMF as a time-dependent state. This study was approved by the Review Board of each Institution and conducted in accordance with the Declaration of Helsinki. Results: Within 768 SMF, 394 were PET and 374 PPV MF. Median follow up time was 14.5 years (range, 0.9-45.9) from ET/PV diagnosis and 3.0 years (range, 0.6-27.3) from SMF diagnosis. We identified 71 patients (9.2% of the entire cohort) who developed a ST (included one multiple myeloma and four lymphoproliferative disorders). We excluded from the analysis myelodysplastic syndromes, acute leukemias, carcinomas in situ, breast fibroadenomas, superficial bladder carcinoma and non-melanoma skin cancers. The most frequent (≥10%) ST subtypes were: breast (17 cases), prostatic (10) and kidney cancer (7). In 11 patients the date of ST occurrence was unreported and therefore they were excluded from time dependent analysis. As for the other 60 cases, 13 (21.7%) were diagnosed before ET/PV development, 22 (36.7%) during the ET/PV phase and 25 (41.6%) after SMF transformation. The cumulative incidence of ST was 0.44% person-year of follow up for ET/PV developing SMF and 0.98% person-year of follow up for SMF. There was a trend of association between male gender and ST occurrence after ET/PV (P=0.054) and after SMF diagnosis as well (P=0.055). No other statistically significant differences in demographics, driver mutations, karyotype, bone marrow fibrosis, and MYSEC-PM strata were found at the time of SMF diagnosis between SMF patients with and without ST. Then, we focused on 165 SMF patients treated with JAK inhibitors (of whom 10 during ET and 15 during PV phase): 128 received ruxolitinib, 11 fedratinib, 11 momelotinib, one XL019 and 14 JAK inhibitors sequentially. We did not find any correlation between JAK inhibitors treatment given at any time point of the follow-up and occurrence of ST (Log-rank P=1). Of note, the four patients with lymphoma did not receive JAK inhibition. In the Pavia cohort, within a median follow up of 4.7 years (range, 0.6-39.7), 24 (3.9%) PV and 40 (4.8%) ET patients developed a ST. The incidence of ST in the Pavia dataset was 0.74% person-year of follow up. We eventually merged the MYSEC and the Pavia cohorts. As for the latter dataset we can not exclude SMF evolution with a longer follow-up, we treated SMF occurrence of the merged group as a time dependent covariate. The probability of developing ST was similar in the group of patients evolved into SMF and in those who did not (P=0.7, Figure 1). Conclusions: This study provides evidence that: 1) the cumulative incidence of ST is about 1% person-year of follow up in SMF patients; 2) JAK inhibitors given during ET/PV or SMF phase are neutral for ST development within the limit of current follow up; 3) developing SMF in patients with PV or ET does not imply a higher risk of ST. These findings highlight the need of studies aimed at identifying patients at higher risk of ST occurrence. Disclosures Rambaldi: Roche: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Omeros: Consultancy; Amgen Inc.: Consultancy; Pfizer: Consultancy. Komrokji:Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding. Gotlib:Kartos: Consultancy; Promedior: Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria, Research Funding; Deciphera: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Kiladjian:Celgene: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Cervantes:Hospital Clinic Barcelona: Employment; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees. Devos:Celgene: Consultancy; Novartis: Consultancy; Takeda: Consultancy. Palandri:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Passamonti:Janssen: Consultancy, Speakers Bureau; Roche: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

scholarly journals Long-Term Outcome of Total Therapy Regimens: Impact of Molecular Subgroups

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3309-3309
Author(s):  
Frits van Rhee ◽  
Maurizio Zangari ◽  
Carolina D. Schinke ◽  
Guido J. Tricot ◽  
Doug Steward ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Low Risk ◽  
Event Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Cure Fraction ◽  
Research Grant

Introduction. Our TT regimens for newly diagnosed multiple myeloma (MM) incorporate novel agents into a sequential treatment program comprising induction, tandem autologous stem cell transplantation and consolidation followed by 3 years of maintenance. Herein, we report the very long-term results in a large cohort of 1986 patients treated on successive TT protocols, the most mature of which (TT1, 2, and 3a) have a median follow-up ranging from 12.8 to 23.1 yrs. Methods. TT1 (1990) was followed by TT2 (1998), which introduced Thalidomide (T) in a randomized fashion. TT3 used bortezomib (V) throughout, with TT3a (2003) and 3b (2006) having different maintenance. TT3a used in year 1 of maintenance V, T and dexamethasone (D) and in years 2 and 3 TD. TT3b introduced lenalidomide (R) during maintenance for 3 years together with V and D. TT4 (2009) only enrolled patients with GEP-defined low risk disease and randomized patients to a standard arm or light arm using a similar regimen as TT3b. TT5 (2009) was specifically designed for patients who have a high 70-gene score and employed a dose dense treatment approach. Finally, TT6 (2009) accrued previously treated, patients irrespective of GEP-defined risk using a treatment schema similar to that used in TT5. Gene expression profiling was used to assign molecular classifications. These include HY (hyperdiploidy), LB (gene expression patterns frequently seen in patients with fewer focal bone lesions), MF (spikes in MAF and MAFB expression), MS (hyperactivation of MMSET +/- FGFR3), PR (over-expression of proliferation-related genes), and CD-1 or CD-2 (different forms of aberrant CCND1 and CCND3 expression). A mixed parametric cure model was used to estimate the proportion of patients with long-term, event-free survival, or the "cure fraction." When using progression free survival (PFS) in the model, the cure fraction is the percent of patients who are likely to never experience relapse based on trends in the survival times that have been observed. When using complete remission duration (CRD) in the model, the model estimates the cure fraction among patients who achieved complete response. Results. The median follow-up on the entire cohort patients was 11.6 years (range: 0.0-27.6) The median overall survival was 9.2 years, with 79.3% and 48.0% having an event-free survival greater than 3 and 10 years, respectively. Overall, patients with GEP70 low risk MM had estimated PFS and CRD cure fractions of 20.1% and 32.7%, respectively. GEP70 high risk MM patients fared much worse with estimated cure fractions of only 8.2 and 11.0%. The estimated PFS- and-CRD based cure fractions increased over time with successive protocols (PFS-cure: 6.0% in TT1 to 27.7% in TT4; CRD-cure: 9.3 to 49.8%). These cure fractions were consistent with the early plateau in the PFS and CRD curves seen at 9 years in TT4 patients. The highest cure fractions were seen in the CD-1 molecular group (34.9 and 40.3%) with intermediate outcomes in the HY (20.1 and 30.0%) and MS (22.8 and 33.5%) groups (Table 1). Surprisingly, low cure fractions were observed in the LB (1.1 and 13.5%) and CD-2 groups (13.5 and 26.4%). CD-1, LB and CD-2 groups had similar 5-yr PFS rates of 60, 60 and 63% respectively, but a steady low rate of relapse was observed in the CD-2 and especially the LB group. These findings were confirmed in a 5-yr landmark analysis showing high PFS and CRD cure fractions in the CD-1 group of 62.7 and 72.3% respectively contrasting to much lower cure fractions in the CD-2 (47.2 and 49.2%) and LB (30.8 and 45.0%) groups. Conclusions. We report excellent long-term outcomes in patients with GEP70 low risk MM and cure fractions in the range of 20-30%. Patients with LB and CD-2 subgroups have lower overall cure rates, despites similar initial 5-yr PFS rates compared to the superior performing CD-1 group, which can be explained by the occurrence of late relapses. Table 1 Disclosures van Rhee: EUSA: Consultancy; Adicet Bio: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy; Kite Pharma: Consultancy; Karyopharm Therapeutics: Consultancy; Castleman Disease Collaborative Network: Consultancy. Walker:Celgene: Research Funding. Davies:Janssen, Celgene: Other: Research Grant, Research Funding; Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor. Morgan:Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: research grant, Research Funding. OffLabel Disclosure: anti-CD38 monoclonal antibody targeting myeloma

scholarly journals Four-Year Interim Analysis of Miroir, a French Multicenter, Non-Interventional Study of Pomalidomide in Relapsed/Refractory Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1836-1836
Author(s):  
Olivier Decaux ◽  
Margaret Macro ◽  
Sophie Gourgou ◽  
Florence Lachenal ◽  
Caroline Bureau Lenoir ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Board Of Directors ◽  
Interim Analysis ◽  
Research Funding ◽  
Routine Clinical Practice ◽  
Interventional Study ◽  
Real World Data ◽  
Advisory Committees ◽  
Refractory Multiple Myeloma

BACKGROUND Real-world data on the use of pomalidomide (POM) for the treatment (Tx) of relapsed/refractory multiple myeloma (RRMM) are limited. The MIROIR study was designed to evaluate POM Tx in routine clinical practice in France. Here, we present results from a prespecified 4-year interim analysis. METHODS MIROIR is a multicenter, observational, ambispective, non-interventional study of POM in routine clinical practice. Adult patients (pts) with MM who initiated POM Tx in France between October 1, 2014, and September 30, 2018, were included. All pts were required to be enrolled in the French IMNOVID® registry. Data were collected from medical records of consenting pts. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. The primary endpoint is progression-free survival (PFS) at 6 months. Key secondary endpoints include time to next Tx (TTNT), overall survival (OS), and safety. This study is ongoing; targeted enrollment is 3000 pts (ClinicalTrials.gov, NCT02902900). RESULTS A total of 2099 pts were included in this analysis (median follow-up: 23.3 months; data cutoff: February 1, 2019). Median age was 70.0 years, and 655 pts (31.2%) were aged ≥ 75 years; 1134 pts (54.0%) were male. Median time from start of first-line Tx to POM initiation was 51.4 months. Pts had received a median of 3 prior lines of therapy (range: 0-9), with 914 (43.5%), 644 (30.7%), 312 (14.9%) and 229 pts (10.9%) receiving ≤ 2, 3, 4, and ≥ 5 prior lines, respectively. From 2014 to 2016, the median number of prior lines of therapy before POM initiation was 3, and from 2016 to 2018, the median was 2. Nearly all pts received prior lenalidomide (LEN; 97.0%) and bortezomib (96.7%). POM was initiated at 4 mg/day in 1635 pts (77.9%) overall and in 1216 pts (84.2%) aged < 75 years and in 419 pts (64.0%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 507 (35.1%) and 732 pts (50.7%) aged < 75 years and in 405 (61.8%) and 62 pts (9.5%) aged ≥ 75 years. Overall, the 6-month PFS rate was 51.7% (95% CI, 49.4%-54.1%). Other key PFS data in pt subgroups are reported in the Table. In the overall population, median TTNT, 12-month OS rate, and median OS were 10.4 months (95% CI, 9.7-11.2), 70.6% (95% CI, 68.5-72.6), and 24.6 months (95% CI, 22.9-not reached), respectively. Among 1164 pts (55.5%) with ≥ 1 adverse event (AE), the most common AEs were neutropenia (290 pts; 24.9%), infections (263 pts; 22.6%), thrombocytopenia (99 pts; 8.5%), and asthenia (87 pts; 7.5%). POM dose was reduced due to an AE in 20.7% of pts; POM Tx was interrupted or discontinued due to an AE in 36.2% and 15.2% of pts, respectively. CONCLUSIONS The results of this interim analysis confirm the efficacy of POM reported in clinical trials and underscore its role in Tx of RRMM, including after LEN Tx. Median PFS in pts with ≤ 2 prior Tx lines was numerically longer than in pts who had more Tx lines, supporting earlier Tx with POM. PFS outcomes were similar regardless of the duration of LEN Tx (< or ≥ 6 months) before initiation of POM and whether pts had received LEN or another Tx as their most recent therapy. The latter finding suggests that POM can be used after relapse or resistance to LEN and that there is no need to replace an IMiD agent with another class of treatment. Disclosures Decaux: Celgene Corporation, Janssen, Takeda, Amgen: Honoraria. Macro:Celgene, Janssen, Amgen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support. Gourgou:Celgene: Employment, Equity Ownership. Lachenal:Celgene: Other: Scientific Comittee's. Stoppa:Celgene: Honoraria. Jaccard:Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Karlin:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fohrer:Celgene: Consultancy, Honoraria. Leleu:Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria.

Open-Label, Multicenter, Phase 1b Study of Daratumumab in Combination with Pomalidomide and Dexamethasone in Patients with at Least 2 Lines of Prior Therapy and Relapsed or Relapsed and Refractory Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 508-508 ◽  
Author(s):  
Ajai Chari ◽  
Sagar Lonial ◽  
Attaya Suvannasankha ◽  
Joseph W. Fay ◽  
Bertrand Arnulf ◽  
...  
Keyword(s):  
Adverse Events ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rate ◽  
Institutional Research ◽  
Advisory Committees ◽  
Multicenter Phase ◽  
Phase 1B ◽  
Grade 3

Abstract Introduction : Daratumumab (DARA) is a human anti-CD38 IgG1κ monoclonal antibody with remarkable safety and activity as monotherapy in heavily treated relapsed and refractory (RR) multiple myeloma (MM) (Lokhorst HM. J Clin Oncol 2014;32 Suppl:abstr 8513. Lonial S. J Clin Oncol 2015;33 Suppl:abstr LBA8512). DARA has demonstrated clinical activity in combination with lenalidomide (LEN) and dexamethasone (D) in relapsed or RR MM (Plesner T. Blood 2014;124(21):84). This ongoing 4-arm, multicenter, phase 1b study (NCT01998971) evaluated the safety and efficacy of DARA in combination with various backbone therapies and pomalidomide plus D (POM-D). Results in newly diagnosed patients treated with DARA and backbone therapies were previously reported (Mateos MV, et al. Haematologica 2015;100(s1):84). Methods : Patients in the DARA + POM-D arm had relapsed or RR MM with ≥2 prior lines of therapy including ≥2 consecutive cycles of LEN and bortezomib. During 28-day treatment cycles patients received DARA 16 mg/kg qw for 2 cycles, then q2w for 4 cycles, and q4w until disease progression (PD). Pomalidomide 4 mg was administered qd for 21 days with D 40 mg qw (20 mg for patients >75 years of age). The primary endpoint was safety and tolerability of DARA in combination with POM-D. Overall response rate (ORR) was a secondary endpoint. Disease responses were evaluated by an independent data safety monitoring board. Results: A total of 77 patients were enrolled into the DARA + POM-D arm. The median (range) age was 64 (35-86) years and the median number of prior therapies was 3.5 (2-10). Sixty-five percent of the patients were refractory to bortezomib, 30% to carfilzomib, 88% to lenalidomide, and 65% to both a PI and IMiD. With a median (range) duration of follow-up of 72 (1-423) days, 28 (36%) patients have discontinued treatment due to PD (15 [20%]), adverse events (AEs; 6 [8%]), death or physician's decision (3 [4%] each), and one (1%) patient withdrawal. The median (range) duration of treatment was 69 days (1-416), and the median (range) number of infusions was 7.5 (1-25). Forty-nine (64%) patients continue on study treatment and enrollment is ongoing. There was little additional toxicity when DARA was added to POM-D other than DARA-specific infusion related reactions (IRRs; 47/77 patients). Most occurred on Cycle 1 Day 1 (45/47 patients), and the most common (>10%) IRRs were chills (13%), cough (13%), and dyspnea (11%). The most common (>10%) and grade ≥3 adverse events (AEs) are presented in Table 1. Five patients died within 30 days of receiving study treatment due to AEs (4[5%]) or progressive disease (1 [1%]). In 53 patients with >1 post-baseline assessment, the ORR was 58.5%, with 3 stringent complete responses (sCR), 1 complete response (CR), 12 very good partial responses (VGPR), 15 partial responses (PR), 2 minimal responses, 18 stable disease, and 2 PD. Many responses deepened over time. Median (range) time to first response was 30 (28-92) days. After a median follow-up of 148 days, 4 out of 31 responders developed PD. Among the evaluable double refractory patients (n = 40), there was 1 sCR, 1 CR, 10 VGPRs, and 11 PRs with an ORR of 57.5%. Conclusions : The addition of DARA to POM-D was well tolerated and did not result in additional toxicities with the exception of DARA-related infusion reactions. Deep and durable responses were observed quickly, along with a high response rate. Study enrollment is ongoing and data will be updated at the meeting. Table 1. Most Common (>10%) Adverse Events (N = 77) Adverse Event, n (%) Any Grade Grade ≥3 Neutropenia 42 (54.5%) 39 (50.6%) Anemia 28 (36.4%) 16 (20.8%) Fatigue 28 (36.4%) 4 (5.2%) Cough 24 (31.2%) 0 Nausea 21 (27.3%) 0 Dyspnea 20 (26.0%) 5 (6.5%) Diarrhea 19 (24.7%) 1 (1.3%) Leukopenia 19 (24.7%) 12 (15.6%) Thrombocytopenia 17 (22.1%) 8 (10.4%) Pyrexia 16 (20.8%) 1 (1.3%) Dizziness 15 (19.5%) 0 Chills 14 (18.2%) 0 Nasal Congestion 14 (18.2%) 0 Upper Respiratory Tract Infection 14 (18.2%) 1 (1.3%) Back Pain 13 (16.9%) 2 (2.6%) Constipation 13 (16.9%) 0 Tremor 13 (16.9%) 2 (2.6%) Insomnia 12 (15.6%) 1 (1.3%) Lymphopenia 11 (14.3%) 7 (9.1%) Muscle Spasms 11 (14.3%) 0 Vomiting 11 (14.3%) 0 Arthralgia 9 (11.7%) 1 (1.3%) Pruritus 9 (11.7%) 0 Throat Irritation 9 (11.7%) 0 Anxiety 8 (10.4%) 0 Headache 8 (10.4%) 0 Hypertension 8 (10.4%) 4 (5.2%) Musculoskeletal Chest Pain 8 (10.4%) 2 (2.6%) Peripheral Edema 8 (10.4%) 1 (1.3%) Disclosures Chari: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Array Biopharma: Consultancy, Other: Institutional Research Funding, Research Funding; Novartis: Consultancy, Research Funding; Biotest: Other: Institutional Research Funding; Onyx: Consultancy, Research Funding. Lonial:Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Suvannasankha:Celgene: Honoraria, Research Funding; Onyx: Honoraria, Research Funding. Arnulf:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Qin:Janssen: Employment. Masterson:Janssen: Employment. Nottage:Janssen: Employment. Schecter:Janssen: Employment. Ahmadi:Janssen: Employment. Weiss:Janssen and Millennium: Consultancy; Janssen and Onclave: Research Funding. Krishnan:Millenium: Speakers Bureau; BMS: Consultancy; Jazz: Consultancy; Janssen: Consultancy; Onyx: Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Lentzsch:Celgene: Consultancy; Janssen: Consultancy; Axiom: Honoraria; Novartis: Consultancy; BMS: Consultancy.

Development of a Novel Patient-Reported Outcome Measure in Haematological Malignancy for Use in Routine Clinical Practice: Item Generation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5985-5985 ◽  
Author(s):  
Pushpendra Goswami ◽  
Sam Salek ◽  
Adele K. Fielding ◽  
Jonathan Kell ◽  
Saad Al-Ismail ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Patient Reported Outcome ◽  
Routine Clinical Practice ◽  
Advisory Committees ◽  
Patient Reported ◽  
Low Prevalence ◽  
The Impact ◽  
Prototype Instrument

Abstract Aims: The impact of haematological malignancies (HM) on patients' health-related quality of life (HRQoL) is still not well understood. The aim of this study was to identify HRQoL issues and symptoms in patients with HM to be included in a new patient-reported outcome measure for use in routine clinical practice. Methods: In a multicentre observational study carried out in the UK, adult patients with various HM, capable of reading English and give written informed consent were recruited from five hospitals in England and Wales. This qualitative study employed semi-structured face-to-face interviews with open-ended questions related to the impact of haematological malignancy and its treatment on HRQoL and symptoms. All the interviews were audio recorded and transcribed verbatim. Content analysis was carried out using the NVivo 11 qualitative analysis software. The themes and the sub-themes generated from the transcribed interviews were discussed during a 2-day "data definition" panel meeting by 2 hematologists, 1 patient research partner, 1 representative of a hematology patient organisation and 3 QoL research experts to select items for inclusion in the prototype instrument. These items will be further re-grouped and refined using cognitive debriefing, content validity and factor analysis. Results: 127 (male=75; mean age = 61.6 years; SD=15.1; median age 65.4 years; and age range =18-88 years) with mean duration of the HM of 3.7 years (SD=4.3; median=2.1 years; and range= 19 days-23 years) were recruited into the study. Diagnoses were: Acute Myeloid Leukaemia (18); Acute Lymphoid Leukaemia (7); Chronic Myeloid Leukaemia (12); Chronic Lymphatic Leukaemia (11); Aggressive Non-Hodgkin Lymphoma (16); Indolent Non-Hodgkin Lymphoma (14); Hodgkin Lymphoma (10); Multiple Myeloma (21); Myeloproliferative Neoplasm (10); and Myelodysplastic Syndrome (8). 383 items were reported by the patients under different themes and subthemes. 117 of these items were reported by more than 5% of the patients. 149 items were selected by the data definition panel to be included in the prototype instrument. The most prevalent QoL issues important to HM patients (Figure 1) were: 'eating and drinking habits (57 patients changed eating and drinking habits; 48 reported loss of appetite; 29 stopped drinking alcohol; and 11 reported increase in appetite); impaired social life and participatory function (86); impaired physical ability or independency (71); disturbed sleep (66); impaired psychological well-being (64); impaired daily activities (61); impaired ability to go on holidays or travelling (60); impaired work life & studies (57 ); impaired sexual life (55); impaired ability to manage finances (34); recreational activities and pastime (32); and relationships (26), from high to low prevalence, respectively. With respect to disease related symptoms, 102 issues were identified, the most prevalent being 'tiredness (65), feeling unwell (28), breathlessness (24), lack of energy (21), back pain (17) and weight loss (17)", from high to low prevalence respectively. Out of 124 treatment related symptoms identified, the most prevalent were: 'tiredness (73); feeling sick (36); lack of energy (20); taste disturbance (20); breathlessness (15); and diarrhoea (15)', from high to low prevalence respectively. Conclusion: The findings of the qualitative and item generation phase clearly indicate that HMs affect patients' QoL significantly. However, in the absence of a validated measure for use in routine clinical practice, this is not captured in a systematic manner. Thus, this highlights the need for the development and validation of a new HM-specific PRO measure for use in such settings. Psychometric testing of the prototype instrument will be carried out to establish the measurement properties of the new HM-specific PRO measure. Figure Figure. Disclosures Salek: EHA: Other: Educational and travel grant. Fielding:Amgen: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Kell:Celgene: Honoraria; Novartis: Honoraria; Sunesis: Equity Ownership. Oliva:Pharma Companies: Honoraria; Italy: Speakers Bureau; Pharma Companies: Consultancy. Ionova:BMS: Research Funding; MSD: Other: lecturer bureau.

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