Treatment Sequencing Patterns in Medicare-Enrolled Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2120-2120 ◽  
Author(s):  
Shuling Li ◽  
Tanya Natwick ◽  
Akeem Yusuf ◽  
Irena Sarah Vidito ◽  
Khalid Mezzi ◽  
...  

Abstract Introduction: Over the last decade, several novel therapies have been approved for multiple myeloma (MM) leading to significant improvement in the prognosis of MM patients. MM patients are often treated with multiple lines of therapy as relapse occurs. With the numerous options of therapeutic agents and novel combinations of regimens, the treatment for MM has become more complicated. However, little is known regarding the treatment sequencing patterns for Medicare patients with MM. In this study, we described the use of drug regimens by lines of therapy and characterized treatment sequences in Medicare patients with MM. Methods: Using a validated algorithm (Princic et al. Blood 2015;126:4521), we identified adult MM patients (≥ 18 years old) in 2008-2011 from the Centers for Medicare & Medicaid Services 100% Hematologic Cancer file (2007-2012) who began first-line (1L) treatment. Patients who advanced to second-line (2L), third-line (3L), and fourth-line (4L) were identified if a 90 day gap in all treatments was observed or when a drug was added to a regimen >90 days after the line index date. Drug regimens were based on National Comprehensive Cancer Network MM treatment guidelines and were identified using National Drug Code and Healthcare Common Procedure Coding System codes. Patients were included in the study if they received monotherapy, doublets, or triplets at 1L. The study period was from the 1L initiation date to the earliest of death, disenrollment from Medicare Parts A, B, and D coverage, receipt of treatments other than the above-mentioned drug regimens, or December, 31, 2012. We described the distribution of type of drug regimens by lines of therapy, overall and by age defined at MM index date, and characterized treatment sequencing patterns for patients who advanced to 2L, 3L, and 4L by type of drug regimens in the prior line of therapy, respectively. Results: In total, 12563 MM patients initiated 1L therapy. Of these, 9% were aged 18-64 years (enrolled in Medicare due to disabilities), 42% aged 65-74 years, and 49% aged ≥ 75 years. Most patients were white (78%) and more than half were female (53%). We identified 5647 (45%), 2243 (18%), and 773 (6%) patients who advanced to 2L, 3L, and 4L, respectively. Overall, doublets were the most common 1L regimen (62%), followed by monotherapy (21%) and triplets (17%). Most common treatments for monotherapy in 1L were dexamethasone (52%), lenalidomide (21%), and bortezomib (17%). The pattern was similar among patients who advanced to a 2L, 3L, or 4L, respectively, though more triplets were used at advanced lines. For 1L therapy, only 12% of patients aged ≥ 75 years received triplets, in contrast to >20% of triplet use in 3L and 4L respectively (Table). Of patients who received monotherapy in 1L and advanced to 2L, 37% continued monotherapy and 63% switched to more dense regimens (doublets, 53%; triplets 10%). Of patients who received doublets in 1L and advanced to 2L, 58% continued doublets, 22% switched to triplets, and 20% to monotherapy. Of patients who received triplets in 1L and advanced to 2L, 26% continued triplets and 74% switched to less dense regimens (doublets, 47%; monotherapy, 27%). Treatment sequencing patterns were similar for patients who advanced to 3L and 4L with monotherapy or doublets in prior lines, while the proportion of patients who repeated triplets increased to about 32% in 3L and 37% in 4L (Figure). Conclusions: Among Medicare patients with MM, doublets were the most frequently used regimens across all lines of therapy, while triplets were used in more advanced lines. Patients on monotherapy or doublets were more likely to retain their treatment pattern when they advance to the next line of therapy, while those on triplet regimen were more likely to switch to a less dense regimen when they advance to their next line of therapy. Fewer patients of older age (75+ years) were prescribed triplet therapies, however triplet use in this patient group increases in more advanced lines. These results provide a baseline description of treatment patterns from which we will be able to benchmark the impact of the recent introduction of novel agents and their use in elderly MM patients. Further studies assessing the comparative effectiveness and benefit-risk of treatment sequences are warranted. Figure Figure. Disclosures Yusuf: Amgen Inc.: Employment, Equity Ownership. Vidito:Amgen Inc.: Employment, Equity Ownership. Mezzi:Amgen Inc.: Employment, Equity Ownership. Werther:Amgen Inc.: Employment, Equity Ownership.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 836-836 ◽  
Author(s):  
Rohan Medhekar ◽  
Dionne Hines ◽  
Sumeet Panjabi ◽  
Tim Welliver ◽  
Xin Wang ◽  
...  

Abstract Introduction: Carfilzomib (K) was first approved in 2012 for the treatment of relapsed/refractory multiple myeloma (RRMM) at a dose of 27 mg/m2 twice weekly (27 BIW). The K dose has since been optimized; carfilzomib plus dexamethasone (Kd) is approved for patients with RRMM at a recommended K dose of 56 mg/m2 twice weekly (56 BIW) since 2016. Recently, the A.R.R.O.W trial showed that Kd 70mg/m2 once weekly (70 QW) significantly improved progression free survival compared to Kd 27 BIW. Considering the study time-period, however, patients are still treated with 27 BIW in the real-world leaving them possibly under-treated. The Kd 27 BIW, corresponds to a cumulative weekly dose (CWD) of K <120mg, while both Kd 56 BIW and Kd 70 QW (optimized dose-56 BIW/70 QW) correspond to a CWD of K >120mg. Therefore, in order to understand the relationship between dose and outcomes we examined the impact of K-dosing (CWD >120mg [optimized dose-56 BIW/70 QW] vs. CWD ≤120 mg [27 BIW]) on time to next treatment (TTNT) and overall survival (OS) among patients treated with Kd regimen. Methods: IQVIA's Oncology Electronic Medical Records database was used to identify patients ≥18 years of age, with a diagnosis of MM between 1/1/2010 and 10/31/2017, receiving Kd regimen in any line of therapy, with ≥ 3 doses of K on or after their K-index date (first administration of K in the Kd regimen, between 1/1/2013 and 10/31/2017). Patients were required to have ≥ 3 doses of K in order to establish continuity and for calculating CWD. CWD was calculated as the cumulative sum of weekly dose of K received by the patient divided by the number of weeks with Kd administration. The first two K doses were excluded from the calculation of CWD as these represent the loading dose. OS and TTNT were compared between patients receiving optimized dose-56 BIW/70 QW vs. 27 BIW. OS was evaluated among the subset of patients with a recorded deceased or alive status and measured from the K-index date until death due to any cause or the end of the study period, where they were censored. TTNT was defined as the time from initiation of the Kd regimen until the start of a subsequent regimen that did not contain Kd (treatment progression). Additionally, a landmark analysis at 12 months from initiation of Kd regimen was conducted to measure the proportion of patients alive and the proportion of patients with treatment progression. Kaplan-Meier analysis was used to estimate OS and TTNT and the log-rank test was used to compare the groups. Adjusted hazard ratios for OS and TTNT were evaluated using Cox models. Results : A total of 1,469 eligible MM patients with ≥3 Kd administrations were identified, of which 129 (8.8%; mean age: 63.5, SD: 9.8) received optimized dose-56 BIW/70 QW and 1,340 (91.2%; mean age: 67.0, SD: 10.4) received 27 BIW. The median follow-up time was slightly over a year for patients in both cohorts. The median K dose was 147.0 mg among patients in optimized dose-56 BIW/70 QW group and 88.1 mg among patients in 27 BIW group. Median OS was not estimable (NE), however, OS for the optimized dose-56 BIW/70 QW group (n=78) was significantly longer than that of the 27 BIW group (n=771; p=0.002) (Fig. 1). The proportion of patients in optimized dose-56 BIW/70 QW group alive at 12 months was 90.3% compared to 79.7% for patients in 27 BIW group respectively. Covariate-adjusted cox model showed that patients in optimized dose-56 BIW/70 QW group had a 64% lower risk of death than patients in 27 BIW group (adjusted HR: 0.364; 95% CI: 0.178-0.745; p = 0.0057, Table 1). TTNT was significantly longer for patients in optimized dose-56 BIW/70 QW group compared to patients in 27 BIW group (p=0.023; median TTNT: 17.5 [95% CI: 14.8-NE] and 13.2, [95% CI: 12.4-14.4], respectively) (Fig. 2). Covariate-adjusted cox model showed that patients in optimized dose-56 BIW/70 QW group had a 33% lower risk of treatment progression than patients in 27 BIW group (adjusted HR: 0.669; 95% CI: 0.483-0.927; p=0.0155, Table 1). Conclusion: Among patients treated with Kd regimen, a smaller proportion were prescribed K at optimized dose-56 BIW/70 QW. Patients receiving the optimized dose-56 BIW/70 QW had significantly improved OS and TTNT compared to those receiving 27 BIW. Our findings suggest that these patient-relevant outcomes may be improved in a vast majority of RRMM patients currently under-treated with carfilzomib by optimizing the dose, taking into consideration patients' comorbidities and ability to tolerate therapy. Disclosures Medhekar: Amgen: Employment, Equity Ownership. Hines:Amgen: Consultancy. Panjabi:Amgen: Employment, Equity Ownership. Welliver:Amgen: Employment, Equity Ownership. Wang:Amgen: Consultancy. Wade:Amgen: Consultancy.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2084-2084
Author(s):  
Robert M. Rifkin ◽  
Eileen Fonseca ◽  
Yaozhu J. Chen ◽  
Patricia S. Fox ◽  
James E. Browning ◽  
...  

Abstract Introduction While novel agents have improved survival over the last decade, multiple myeloma (MM) remains incurable. Carfilzomib (CFZ), a second-generation proteasome inhibitor, was approved in July 2012 by the US Food and Drug Administration and had a label change in July 2015. During this study's data period, the label recommended Cycle 1 dose at 20 mg/m2/day and if tolerated increase Cycle 2 dose and subsequent cycles doses to 27 mg/m2/day. The purpose of this study is to assess baseline characteristics, CFZ dosing patterns and survival among MM patients in a US community oncology setting. Methods A retrospective study of MM patients from US Oncology Network practices that fully implemented McKesson Specialty Health's iKnowMed (iKM) oncology-specific electronic health records database was conducted on patients whose first treatment of CFZ (index) occurred between Jul-2012 and Nov-2014. Patients were eligible if they had a documented initial MM diagnosis date and had their first CFZ cycle documented in the database. Additionally, patients were required, before Dec-2014, to have either another visit to the practice post-index or a record of death and not have participated in interventional clinical trials during the previous 6 years. Data on eligible patients were collected up to March 2015. The death event was defined by the Social Security Death Index, supplemented by iKM; patients without the event were censored at the date of last observed visit. To adjust for clinical practice variations, a 10% variability was allowed for the recommended daily dose levels of 20 mg/m2 and 27 mg/m2. A subgroup was defined for patients with a 2nd cycle: "escalators" if they received 20 mg/m2/day doses throughout Cycle 1 and increased to 27 mg/m2/day on the first dose of Cycle 2; "non-escalators" if they received only 20 mg/m2 doses throughout Cycle 1 and did not increase to 27 mg/m2 on the first dose of Cycle 2; receiving any dose not equal to 20 or 27 mg/m2 were classified into "other". Survival after index was estimated using the Kaplan-Meier method with 95% confidence intervals (CI). A multivariable Cox proportional hazards (PH) model was conducted to evaluate the impact of escalation on survival accounting for selected baseline demographic and clinical characteristics. Results The cohort of 718 CFZ patients were identified with a median (interquartile range [IQR]) age of 68 (61-75) years at index, 57% (n=409) were male, and 12% (n=87) were Black and 77% (n=551) were Caucasian. At initial MM diagnosis, 19%, 27% and 42% were ISS Stage I, II, and III, respectively. Median (IQR) time from MM diagnosis to index was 3.6 (1.9-5.8) years. At index, 66% of patients had an ECOG performance status of 0-1, 21% of 2, and 2% of 3+; 54% (n=369) had moderate to severe renal impairment (eGFR<60 mL/min per 1.73 m2). Ninety percent (n=644) of patients started CFZ at 20 mg/m2, 4% (n=27) at 27 mg/m2 and 4% (n=25) at 15 mg/m2. Patients had a median (IQR) of 4 (2-7) cycles of CFZ and 45% (n=321) escalated to ≥27 mg/m2. Among these 321 patients, median (IQR) time to first escalation was 30 (28-56) days with 60% escalating in Cycle 2. The subgroup defined in "Methods" included 605 patients: 148 (24%) escalators, 342 (57%) non-escalators, and 115 (19%) other. Median (95% CI) duration from index to death was 21 (17.5-23.2) months. Unadjusted overall survival (OS) was significantly lower among non-escalators compared to escalators (log-rank p=0.024) [Figure 1]. Survival rates (95% CI) for non-escalators and escalators were 68% (62-74%) and 75% (66-82%) at year 1 and 42% (33-50%) and 61% (49-71%) at year 2, respectively. Within the multivariable Cox model, escalators showed a 33% significantly lower risk of death compared to non-escalators (HR=0.67, p=0.03) while also accounting for race, sex, age group, renal function per EGFR, and MM chain type. Other significant variables in this model were: EGFR < 15 and 15-29 vs 30-59 ml/min per 1.73m2 (HR=2.79, p<0.01; HR=1.64, p=0.04, respectively) and lambda vs kappa light chain (HR=1.55, p=0.03). Conclusions These results indicate escalation of CFZ at first dose of Cycle 2 is associated with better survival than dosing at 20 mg/m2 in Cycle 1 but not escalating at the start of Cycle 2. More research is needed to assess factors that impact physician decision-making on dose escalation to better inform physicians to improve the quality of multiple myeloma care. Disclosures Rifkin: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fonseca:McKesson Specialty Health, which received funding to conduct this research: Employment, Equity Ownership. Chen:Onyx Pharmaceuticals: Employment. Fox:McKesson Specialty Health, which received funding to conduct this research: Employment. Browning:Onyx Pharmaceuticals, An Amgen Subsidiary: Employment. Cong:Onyx Pharmaceuticals: Employment, Equity Ownership.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4219-4219 ◽  
Author(s):  
Shaji K. Kumar ◽  
Ravi Vij ◽  
Jonathan L. Kaufman ◽  
Joseph R. Mikhael ◽  
Thierry Facon ◽  
...  

Abstract Background: The anti-apoptotic protein BCL-2 has been implicated in mediating the survival of multiple myeloma (MM) cells. Venetoclax is a potent, selective, orally bioavailable small-molecule BCL-2 inhibitor. Venetoclax induces cell death in MM cell lines in vitro and primary MM samples ex vivo. Certain genetic subtypes of MM cells are particularly sensitive to venetoclax, including t(11;14) cells, which express a high ratio of BCL2 to MCL1 (venetoclax resistance factor). The current Phase 1 study evaluates safety, efficacy, and pharmacokinetics (PK) in patients (pts) with relapsed/refractory MM. Methods: Primary objectives are to evaluate safety, PK, and recommended phase two dose; other objectives include assessing preliminary efficacy and the impact of chromosomal abnormalities. In dose-escalation (DE) cohorts, venetoclax was given orally daily at 300, 600, 900, or 1200 mg after a 2-week dose ramp-up (3+3 design). Patients in the safety expansion (SE) cohort received 1200 mg daily after ramp-up. All patients were monitored for tumor lysis syndrome (TLS). Results: As of June 17, 2015, 37 patients were enrolled in the study: 30 from DE cohorts and 7 from the SE. Median (range) age was 66 years; 19 (51%) were female. Fourteen were ISS stage I, 13 stage II, 8 stage III, 2 unknown. The median (range) number of prior lines of therapy was 6 (1-19). Thirty-two had prior bortezomib (20 refractory), 35 lenalidomide (18 refractory), and 26 had prior stem cell transplant. Fourteen patients had t(11;14), 4 had t(4;14), 5 had del 17p, and 17 had del 13q. Adverse events (AEs) in ≥20% of patients were nausea (49%), diarrhea (38%), vomiting (30%), anemia (27%), fatigue (24%). Grade 3/4 AEs (≥10%): thrombocytopenia (22%), anemia (19%), neutropenia (11 %). Serious AEs (≥2 patients): pyrexia (n=3), cough, malignant neoplasm progression, and sepsis (2 each); 2 (upper abdominal pain and anemia) were possibly related to venetoclax. Thirty (81%) patients have discontinued venetoclax: 24 due to PD, 3 for AEs (worsening shortness of breath, hypokalemia, and nausea), 2 withdrew consent, 1 due to death (brain hemorrhage following injury). Four deaths occurred (2 due to PD, 1 due to brain hemorrhage, 1 due to pneumopathy). Two of the 6 patients in the 600 mg cohort experienced DLTs of upper abdominal pain and nausea with abdominal pain. No patients met the criteria for laboratory or clinical TLS. Based on preliminary PK (n=21), the mean Cmax and AUC24 were ~dose-proportional at all studied doses (300, 600, 1200 mg) except 900 mg, and dose-normalized venetoclax exposure in MM was similar to that in CLL and NHL pts. Thirty-two of the 37 patients were evaluable for preliminary efficacy (Table). Two patients, both t(11;14), achieved a complete response (1 at 600 mg and 1 at 900 mg). Responses were first achieved at 1.8 and 1.1 months and were maintained for 9.7 and 9.0 months, respectively (900 mg pt remains in CR). Among the 16 patients receiving 1200 mg in the DE or SE cohort, 6 of whom had t(11;14), 5 achieved SD, 6 experienced PD, and 5 are not yet evaluable. Conclusions: Venetoclax monotherapy had a tolerable safety profile in heavily-pretreated relapsed/refractory MM, and no new safety signals were observed compared to other venetoclax studies. The study continues to enroll in the SE cohort at 1200 mg. Responses (including CR) and longer time on venetoclax were observed in t(11;14) patients. These early results suggest that venetoclax has single agent activity, most prominently in t(11;14) patients. Figure 1. Figure 1. Disclosures Kumar: Celgene: Research Funding; Millenium/Takeda: Research Funding; Onyx: Research Funding; AbbVie: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation,; Skyline, Noxxon: Honoraria. Off Label Use: Venetoclax is an investigational drug that is not yet approved in this indication.. Vij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy. Kaufman:Janssen: Consultancy; Spectrum: Consultancy; Merck: Research Funding; Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; Novartis: Research Funding; Onyx: Research Funding. Mikhael:Sanofi: Research Funding; AbbVie: Research Funding; Celgene: Research Funding; Onyx: Research Funding. Moreau:Takeda: Other: Adboard; Janssen: Other: Adboard; Celgene: Other: Adboard; Novartis: Other: Adboard; Amgen: Other: Adboard. Alzate:AbbVie: Employment, Equity Ownership. Morris:AbbVie: Employment, Equity Ownership. Ross:AbbVie: Employment, Equity Ownership. Dunbar:AbbVie: Employment, Equity Ownership. Zhu:AbbVie: Employment, Equity Ownership. Maciag:AbbVie: Employment, Equity Ownership. Agarwal:AbbVie: Employment, Equity Ownership. Leverson:AbbVie: Employment, Equity Ownership. Enschede:AbbVie: Employment, Equity Ownership. Humerickhouse:AbbVie: Employment, Equity Ownership. Touzeau:AbbVie: Research Funding.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4223-4223 ◽  
Author(s):  
Andrzej Jakubowiak ◽  
Jagoda Jasielec ◽  
Cara A. Rosenbaum ◽  
Jeffrey A Zonder ◽  
Craig E. Cole ◽  
...  

Abstract Background There is an increasing number of multiple myeloma patients (pts) refractory to currently available drugs, including the proteasome inhibitors bortezomib and Carfilzomib (CFZ), necessitating development of novel effective therapeutics. Pre-clinical evaluation of selinexor, a novel orally available selective inhibitor of nuclear export (SINE), in human myeloma cell lines (HMCL), primary plasma cells derived from myeloma patients, and HMCL tumor-bearing mice demonstrated synergistic myeloma cell death with CFZ (Rosebeck et al. ASH 2013) and the ability to overcome resistance to CFZ (Rosebeck et al. ASH 2014). Aims The primary objective is to assess the maximum tolerated dose (MTD) of selinexor and CFZ in combination with DEX in RRMM pts and to provide preliminary evaluation of efficacy of this novel triplet regimen. Methods Pts with RRMM, including CFZ-refractory pts, who have failed at least two prior treatment regimens of myeloma therapy, were eligible for enrollment. Dose escalation follows the 3+3 design with pts receiving 30 mg/m2 - 40 mg/m2 selinexor PO on days 1, 3, 8, 10, 15, 17; 20 mg/m2 - 56 mg/m2 CFZ given IV on days 1, 2, 8, 9, 15, 16, and DEX PO 20/10mg (cycles 1-4/cycles 5+) in 28-day cycles. At least 12 and up to 48 pts are planned for evaluation. Dose Limiting Toxicities (DLT) are measured for the Cycle 1 as well as Day 1 of Cycle 2. Dose modifications are allowed to manage toxicities. Response was assessed by IMWG criteria plus near complete response (nCR). Results As of July 1st, 2015 the study has enrolled 8 pts, 5 pts were treated at dose level 1 (30 mg/m2 selinexor, 20/27 mg/m2 CFZ, 20/10 mg DEX) and 3 patients were treated at dose level 2a (30 mg/m2 selinexor, 20/36 mg/m2 CFZ, 20/10 mg DEX). Pts had median age of 65.5 (range 55-73) and a median of 5 prior treatment regimens (range 2-5). Six pts were refractory to CFZ combinations at their last line of therapy, including 4 to CFZ, pomalidomide (POM), and DEX. Of the 2 remaining pts, 1 was refractory to high dose CFZ with DEX in prior line of therapy and both were refractory to last line of therapy. Six pts were DLT-evaluable and two pts required replacement for DLT evaluation (1 pt had DEX reduced in cycle 1 not due to DLT; 1 pt did not receive all scheduled cycle 1 doses due to progressive disease). There have been no DLTs and MTD is not yet established. Adverse events (AEs) were reversible and managed with concomitant therapy. G3/4 hematologic AEs include thrombocytopenia (75%), neutropenia (50%), leukopenia (37.5%), lymphopenia (25%), and anemia (25%). The most common G3/4 non-hematologic AEs included fatigue (25%) and upper respiratory tract infection (25%). The most common G1/2 AEs are fatigue (75%), dyspnea (62.5%), nausea (62.5%), anemia (50%), leukopenia (50%), and thrombocytopenia (50%). Response rates for all enrolled pts are 87.5% ≥MR, 75% ≥PR, 12.5% ≥VGPR. Responses occurred rapidly; after 1 cycle: 75% ≥MR, 63% ≥PR, 12.5% VGPR. As of the cut off date, 4 pts have progressed (after 1, 2, 4, and 4 months) and 4 pts remain on treatment (10+, 1+, 1+, and 1+ months); 1 pt did not respond and died due to progression of disease. Conclusions Although still very early, the combination of selinexor, CFZ, and DEX demonstrates encouraging activity with 75% PR or better and no unexpected toxicities in highly refractory MM pts, including those previously refractory to CFZ. Responses in pts refractory to very active CFZ combinations in the last line of therapy suggest that this regimen has the ability to overcome CFZ resistance. Disclosures Jakubowiak: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SkylineDx: Membership on an entity's Board of Directors or advisory committees; SkylineDx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: institutional funding for support of clinical trial conduct, Speakers Bureau; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Off Label Use: The combination of Carfilzomib and Selinexor is being used for the treatment of Multiple Myeloma. Rosenbaum:Celgene: Speakers Bureau. Zonder:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: research support; Prothena: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Chari:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array BioPharma: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Millenium/Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Rashal:Karyopharm Therapeutics Inc: Employment. Youssoufian:Karyopharm Therapeutics Inc: Employment. Henry:Karyopharm: Employment, Equity Ownership. Shacham:Karyopharm: Employment, Equity Ownership. Kauffman:Karyopharm: Employment, Equity Ownership.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 405-405 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Teresa Petrucci ◽  
Robin Foà ◽  
John V. Catalano ◽  
Martin Kropff ◽  
...  

Abstract Introduction In a phase 3 trial of transplant non-eligible elderly (≥ 65 yrs) patients (pts) with NDMM, the combination of melphalan-prednisone-lenalidomide (LEN) followed by LEN maintenance (MPR-R) reduced the risk of progression by 60% compared with 9 cycles of MP (HR=0.40; P < 0.001) and by 51% compared with 9 cycles of MPR (HR=0.49; P < 0.001) (Palumbo, NEJM. 2012). The progression-free survival (PFS) benefit was seen in all patient types. With a median follow-up of 53 mos, the median overall survival (OS) was similar across the 3 treatment (Tx) groups (54 mos for MPR-R vs. 52 mos for MPR vs. 55 mos for MP) (Dimopoulos, ASH 2012; abstract 944). The similar OS benefit seen across the 3 arms could be due in part to the availability of more effective Tx options in subsequent lines of therapy. Assessment of PFS2, defined as the time from initial randomization to time of objective disease progression (PD) after next-line of therapy or death from any cause, has recently been proposed as a surrogate for OS, particularly for trials evaluating maintenance Tx (EMA guideline, www.ema.europa.eu). Therefore, data from MM-015 were analyzed to estimate PFS2 in pts treated with MPR-R, MPR, or MP. Methods The MM-015 study design has been previously described (Palumbo, NEJM. 2012). Refractory multiple myeloma pts who progressed during MM-015 study could receive LEN 25 mg (D1–21/28-day cycle) ± dexamethasone 40 mg (on days 1–4, 9–12, and 17–20) as part of an open-label extension phase, or any other anti-myeloma Tx outside of the protocol as part of the follow-up phase. The data of PD following 2nd-line Tx was not collected prospectively; therefore, the start of 3rd-line Tx was used as a surrogate for analyzing the PFS2 endpoint. The assessment included data up to July 31, 2012 (median follow-up: 53 mos after initial randomization). Results A total of 459 pts were randomized to MPR-R (n= 152), MPR (n= 153), or MP (n= 154). At the time of the data cut-off, fewer pts in the MPR-R group had started 2nd-line Tx (53%) compared with the MPR and MP groups (77% and 82%, respectively) due to the improved PFS seen with MPR-R in the 1st-line setting. Most pts in the MP group “crossed over” to receive LEN as 2nd-line Tx (72%); choice of 2nd-line Tx in the MPR-R group was heterogeneous (Table). Median PFS2 was significantly higher with MPR-R (39.7 mos) vs. MP (28.5 mos; HR=0.71; log-rank P = 0.013) (Figure). The safety profile of continuous therapy with LEN was predictable and manageable with little evidence of cumulative toxicity and low second primary malignancy risk (Delforge, IMW 2013: abstract O-17). Conclusion PFS2 was markedly improved in the MPR-R group vs. the MP group. LEN provided a durable progression-free interval also when including the impact of 2nd-line Tx, confirming the clinical benefits of continuous LEN Tx. The benefit of MPR-R was apparent regardless of subsequent Tx; long-term treatment with LEN did not affect the efficacy of subsequent therapy. Use of continuous LEN in the 1st-line setting in combination with MP is more beneficial than sequential use of MP and LEN. PFS and PFS2 were improved with MPR-R; OS was similar among the 3 Tx groups; the reason for this is unclear, but may be related to the impact of subsequent Tx (i.e., 3rd and 4th line), which was more frequently needed in the MPR and MP groups. Disclosures: Dimopoulos: Orthobiotech: Honoraria; Celgene Corporation: Honoraria. Off Label Use: Lenalidomide in the frontline and maintenance treatment of multiple myeloma. Petrucci:Celgene Corporation: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Catalano:Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Yu:Celgene Corporation: Employment, Equity Ownership. Grote:Celgene Corporation: Employment, Equity Ownership. Jacques:Celgene Corporation: Employment, Equity Ownership. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4770-4770
Author(s):  
Shivani Pandya ◽  
Zoe Clancy ◽  
Sulena Shrestha ◽  
Li Wang ◽  
Onur Baser

Abstract Background: For decades, CRAB criteria (hypercalcemia, renal impairment, anemia, and bone disease) have been used to diagnose multiple myeloma (MM), but little is known about the economic burden of CRAB in patients with MM who have relapsed. The only category 1 doublet regimens recommended by NCCN Guidelines for non-transplant candidates are lenalidomide-based (NCCN Myeloma v4.2018). This study aims to evaluate CRAB event rates and the associated economic burden among newly diagnosed MM (NDMM) patients on doublet therapy who were not eligible for stem cell transplant (SCT) and were followed to next line of therapy. Methods: This retrospective study identified patients with ≥ 2 claims of MM (ICD-9-CM code: 203.0x; ICD-10-CM code: C90.0x) ≥ 30 days apart and ≥ 1 treatment (first claim date was used as index date) between January 1, 2011 and December 31, 2015 from the Medicare database. Eligible patients were required to have continuous enrollment from 6 months pre-index or first MM diagnosis date until ≥ 12 months post-index date unless patients died < 12 months post-index date (the follow-up period); ≥ 1 full cycle of therapy; no evidence of prior MM diagnosis or treatment (including autologous SCT [ASCT]); and no evidence of ASCT in the follow-up period. First line of therapy (LOT1) included all treatments prescribed within 60 days of the index date, and patients were included in the doublet therapy cohort based on the index treatment regimen. Progression to a subsequent LOT (LOT2) was defined by the earliest occurrence of an addition or switch to new non-maintenance treatment > 60 days post-index date, restart of any non-maintenance MM treatment after a > 180-day gap, or a dose increase from maintenance to relapse therapy. CRAB event rate per 1,000 person-years (PYs), CRAB event-related healthcare resource utilization (HRU) per patient per month (PPPM), and costs PPPM were evaluated during the LOT1 (the time from index date to end of LOT1) and LOT2 (the time from initiation of LOT2 to end of LOT2) among patients on doublet therapy with LOT1 and those who progressed to LOT2, respectively. Mean was calculated for the continuous variables, while categorical variables were presented as percentage values. Since the LOT2 population was a subset of the LOT1 population and they were not mutually exclusive cohorts, no statistical comparisons were made. Results: The study included 4,970 patients with MM not eligible for ASCT, of which 3,065 (61.7%) patients were prescribed doublet therapy in LOT1. Among these patients on doublet therapy, 1,122 (36.6%) initiated LOT2. The mean age was approximately 77 years, and most patients were white (LOT1, 77.0%; LOT2, 79.7%). The majority of the patients had hypertension (LOT1, 88.3%; LOT2, 86.1%), followed by anemia (LOT1, 79.0%; LOT2, 75.6%) and osteoarthritis (LOT1, 75.7%; LOT2, 76.7%), as comorbidities during the 6 months prior to the index date. CRAB event rates declined from LOT1 to LOT2, with the highest event rate per 1,000 PYs observed for anemia (LOT1, 1,965.1; LOT2, 1,808.2), followed by bone disease (LOT1, 258.1; LOT2, 244.1), renal impairment (LOT1, 167.9; LOT2, 159.9), and hypercalcemia (LOT1, 106.9; LOT2, 99.6); a decline in event rate was observed from LOT1 to LOT2 (Figure 1). CRAB event-related HRU PPPM increased from LOT1 to LOT2, including number of inpatient visits (LOT1, 0.1; LOT2, 0.2), length of inpatient stay (LOT1, 0.8 days; LOT2, 1.0 days), and number of outpatient hospital visits (LOT1, 2.0; LOT2, 2.2). However, the number of outpatient office visits PPPM decreased from LOT1 to LOT2 (LOT1, 0.9; LOT2, 0.8). Similarly, there was a trend toward increased CRAB event-related healthcare costs PPPM from LOT1 to LOT2 (Figure 2) including inpatient (LOT1, USD 1,548; LOT2, USD 2,031), outpatient hospital (LOT1, USD 214; LOT2, USD 301), outpatient office (LOT1, USD 77; LOT2, USD 89), and total medical costs (LOT1, USD 2,120; LOT2, USD 2,593). Conclusions: This study shows that CRAB events were more expensive to treat as patients relapse. Delaying disease progression may be associated with lower HRU and potential cost savings, thereby reducing the burden of MM. A potential limitation of this study is that claims data do not include clinical parameters. Future studies should be considered to evaluate the impact of age and comorbidities on the economic burden associated with CRAB events. This study also highlights the value of delaying progression and the time to next treatment. Disclosures Pandya: Celgene Corporation: Consultancy; STATinMED Research: Employment. Clancy:Celgene Corporation: Employment, Equity Ownership, Research Funding. Shrestha:STATinMED Research: Employment, Equity Ownership. Wang:STATinMED Research: Employment, Equity Ownership.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5676-5676 ◽  
Author(s):  
David Robinson ◽  
Satyin Kaura ◽  
Daniel Kiely ◽  
Mohamad A. Hussein ◽  
Knar Nersesyan ◽  
...  

Abstract BACKGROUND: Multiple myeloma survival has significantly improved with the introduction of new therapeutic classes in the early 2000s. The magnitude of improvement in survival with better tolerated therapy is essentially transforming the disease from an acute condition, to a potentially manageable chronic disease . The impact of further advances in multiple myeloma therapy is not yet known but can be projected based on analysis of historical data and positive outcomes that are expected for future clinical trials. METHODOLOGY: Analysis of data from the Surveillance, Epidemiology and End Results (SEER) were performed using SEERStat software. The first part of this analysis compares the median relative survival, based on cohort analysis, and five year relative survival, based on period analysis, for different time periods that coincided with the introduction of newer, better tolerated, more effective therapies for treating multiple myeloma. The second part of this analysis attempts to estimate future changes in survival, that may potentially result from additional disease modifying therapies planned to become available over the next 5-10 years. This will be accomplished through analysis of evidence-based metrics including extrapolation from early phase clinical trial data and validation with key opinion leaders. RESULTS: Median, cumulative and 5 year relative survival of multiple myeloma have improved over the last decade primarily as a result of the introduction of newer therapies such as thalidomide, lenalidomide and bortezomib. Based on analysis of SEER data, median relative survival from the 1980s to 2000 showed modest changes, averaging approximately 30 months through the two decades. Thereafter, median survival increased to nearly 50 months by 2007 (FIGURE 1). Five year relative survival improved from about 30% in 1990 to over 46% in 2010 (FIGURE 2). SUMMARY: This analysis highlights the dramatic improvements in multiple myeloma survival over the last three decades in the U.S., and demonstrates the transformative impact and value of novel therapies for multiple myeloma. The most substantial improvements were observed during the period between 2001 and 2007, when multiple myeloma median survival rates increased by 45%. This improvement has predominantly been driven by the introduction of novel classes of drugs and agents, including immunomodulatory and proteasome inhibitors. Over the next 10 years we expect to see a similar trend, where further advances in the treatment of multiple myeloma will yield additional novel therapies that could result in improvements of comparable or better magnitude. FIGURE 1 FIGURE 1. FIGURE 2 FIGURE 2. Disclosures Kaura: Celgene: Employment, Equity Ownership. Kiely:Celgene: Employment, Equity Ownership. Hussein:Celgene: Employment, Equity Ownership. Durie:Celgene: Advisory Board Celgene, IRC Onyx, DMC Millennium, IRC J&J Other.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3294-3294
Author(s):  
Steven R Arikian ◽  
Gary Binder ◽  
Craig Gibson ◽  
X Henry Hu ◽  
Yasir Nagarwala ◽  
...  

Abstract Introduction. A previous study of patients (pts) with newly-diagnosed multiple myeloma (NDMM) showed that initial high monthly total costs declined over time until returning near initial levels upon pts advancing to later lines of treatment (Tx) at disease progression (Arikian, CMRO 2015). However, the longer-term economic implications of the choice of first-line Tx, regardless of subsequent Tx regimens, have not been described. We utilized an intent-to-treat approach to further evaluate and compare the total costs of NDMM patient cohorts initiated on Lenalidomide (LEN) or Bortezomib (BORT)-based Tx and followed these patients over 54 months. Methods: A retrospective analysis was performed using a large US medical and pharmacy claims database, covering > 25 million commercial and Medicare lives annually. NDMM patients were defined as having ≥ 2 outpatient claims or ≥ 1 inpatient medical claim with a diagnosis of MM (ICD-9-CM code 203.0X), with the first such claim used to define the index date. Inclusion criteria required ≥ 12 months' pre-index and ≥ 6 months' post-index continuous enrollment from 2006 - 2013, and evidence of initiation of a subsequent line of therapy. Pts with claims for stem cell transplantation (SCT) or receiving concurrent LEN plus BORT as first-line Tx were excluded. The analysis focused on cohorts of NDMM pts receiving LEN or BORT-based first line Tx, who progressed to one or more subsequent lines of Tx, using time to next therapy (TTNT) as a proxy for progression. Pts receiving LEN or BORT-based first line Tx were randomly matched 1:1 on age (+/- 3 years at index), sex, baseline Charlson comorbidity score (+/- 1), and presence of renal disease. Using methods similar to those described by Gaultney(J Clin Pharm Ther, 2013), pts' average monthly costs and standard errors were determined, including medical and pharmacy costs, and total cost patterns were calculated from first line Tx initiation until the end of patient eligibility or 54 months. Results: 1,181 NDMM pts receiving LEN (N=444) or BORT-based (N=737) first line Tx with complete data available through initiation of subsequent line of Tx were identified. After matching, 856 NDMM patients remained (428 LEN, 428 BORT). Monthly total direct medical plus pharmacy costs for these pts were in excess of $12,000 at initiation. Total monthly costs declined quarterly for each cohort until the median TTNT was reached (20 months for BORT; 37 months for LEN). As increasing numbers of pts in each cohort then advanced to subsequent lines of therapy, costs of those patients began to offset continued cost declines for pts still on first line of therapy. Over the full 54 month follow-up period, total monthly costs averaged $8,324 (SE = $370.30) for pts initiated on LEN vs. $10,728 (SE = $500.55) for pts initiated on BORT (p-value <0.001). Medical costs represented 54-57% of total monthly costs for each cohort. In each cohort, the most common Tx option upon disease progression was to switch to the other regimen. Conclusions: For a matched population of NDMM pts followed continuously for 54 months, initiation on LEN- versus BORT-based Tx without SCT was associated with an average of $2,404 lower monthly direct total costs. Following initiation of first-line therapy, total monthly costs per pt declined quarterly until initiation of the next line of Tx. Cumulative costs over the 54-month period were over $120,000 lower per pt in favor of the LEN cohort, influenced by more rapid advancement to subsequent Tx in the BORT cohort, and the associated higher costs. Based on second-line Tx patterns, this analysis also suggests that a sequence of LEN in first line followed by BORT in second line is associated with lower costs over time compared to the reverse sequence. Due to the nature of retrospective claims, some underlying differences may remain between the two cohorts even after matching. Figure 1. Direct monthly costs (medical and pharmacy) for LEN- and BORT-initiated patients and savings attributed to LEN-initiated patients Figure 1. Direct monthly costs (medical and pharmacy) for LEN- and BORT-initiated patients and savings attributed to LEN-initiated patients Disclosures Arikian: Genesis Research: Consultancy. Binder:Celgene Corporation: Employment, Equity Ownership. Gibson:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Nagarwala:Celgene Corporation: Employment. Hussein:Celgene Corporation: Employment, Equity Ownership. Corvino:Genesis Research LLC: Consultancy. Lee:Genesis Research LLC: Consultancy. Surinach:Genesis Research LLC: Consultancy. Kaura:Celgene Corporation: Employment. Usmani:Onyx: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria; Janssen: Research Funding.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3290-3290
Author(s):  
Jenny Willson ◽  
Amanda Bruno ◽  
Joanna Opalinska ◽  
Jeannene Nelson ◽  
Orsolya Lunacsek ◽  
...  

Abstract Introduction: Limited real-world data exist on treatments for relapsed/refractory multiple myeloma (RRMM) since the approval of several new agents. This study assessed treatment patterns and outcomes of patients with RRMM receiving ≥2 lines of therapy in US community oncology practices. Methods: A chart review was conducted in patients ≥18 years with MM diagnosed January 1, 2011-May 31, 2017, from a large electronic medical record database. Patient data were examined from the date of initiation of first-line therapy (1LT) for MM until death, loss to follow-up, or study end date, whichever was earliest. This study was hypothesis generating, thus no statistical tests were performed. Descriptive statistics were used to describe baseline demographic/clinical characteristics, treatment patterns, median progression-free survival (mPFS) and median overall survival (mOS) for the overall RRMM population. Patients were then stratified into "older" vs. "newer" treatment cohorts based on whether the drugs used in each line of therapy were approved before, or after 2013. Results: Of 1005 charts reviewed, 456 patients had received ≥2 lines of therapy and were included in the chart review study (median age at diagnosis: 70.4 years; females: 39.5%, males 60.5%; bone involvement at diagnosis: 66.0%; International Staging System stage within 1 month of diagnosis: I 28.7%, II 27.9%, III 43.4%; 183 (40.1%) patients received 3LT, 75 (16.4%) 4LT, and 29 (6.4%) 5LT. 1LT was dominated by bortezomib (BTZ), lenalidomide (LEN), and the combination of the two, with 93.3% of patients using these agents as 1LT and 69.8% of patients as 2LT. In 3LT and beyond, there was greater use of newly approved drugs (approved since 2013) compared with 1LT and 2LT; pomalidomide (14.8% 3LT, 17.3% 4LT, 17.2% 5LT), carfilzomib (19.1% 3LT, 13.3% 4LT, 17.2% 5LT), elotuzumab (2.2% 3LT, 4.0% 4LT, 3.4% 5LT), panobinostat (0% 3LT, 2.7% 4LT, 3.4% 5LT), daratumumab (6.6% 3LT, 13.3% 4LT, 17.2% 5LT), and ixazomib (0% 3LT, 1.3% 4LT, 3.4% 5LT) with the exception of the BTZ/LEN combination. However, patients receiving either BTZ, LEN, or both in combination as 1LT or 2LT often received the agent(s) as re-treatment in lines 2-6 (46.2%-55.6%). Median time on treatment decreased from 7.5 months in 1LT to ≤2.3 months in 4LT and 5LT, and median treatment-free intervals decreased from 1.6 months between 1LT and 2LT to 0.5 months between 4LT and 5LT. The most common reason for discontinuation was disease progression and drug toxicity/intolerability. The most commonly reported adverse events (AEs) for all lines of therapy were fatigue (71.6%-78.3%), bone pain (38.5%-69.1%) and anemia (53.8%-69.3%). AEs were generally constant across lines of therapy, except for bone pain, anemia, and neuropathy, which broadly decreased with increasing line of therapy. Overall, mPFS ranged from 12.0 months in 1LT to 3.5 months in 5LT and mOS ranged from 48.2 months in 1LT to 5.8 months in 5LT (Figure 1). A trend for increased mPFS and mOS with newer vs. older drugs was observed across treatment lines. The magnitude of the "new" treatment benefit on mPFS was pronounced in 1LT. Conclusions: Forty percent of patients received therapy beyond 2lines demonstrating a great unmet need in the treatment of RRMM. While BTZ and LEN were predominant in 1st and 2nd lines, substantial fragmentation was seen in ≥3 line, highlighting the lack of defined treatment pathways for these patients. The results further indicated that treatments beyond 2LT offer shorter benefit as disease progresses; median time on treatment and mPFS decreased as treatment line increased. Also, median PFS and OS in this real-world analysis were also slightly lower than that observed in recent clinical trials of novel agents, which is consistent with other real-world studies. While there remains a need to replicate these results within a larger dataset where statistical comparisons could be made and confounding factors controlled for, the trends observed in this study suggest improved PFS and OS outcomes may be associated with newly approved treatments. In particular, the trends suggested that newer treatments may have a greater mPFS benefit vs. older treatments if used in earlier lines of treatment. Funding: GSK (HO-17-17767) Disclosures Willson: GlaxoSmithKline: Employment, Equity Ownership. Bruno:GlaxoSmithKline: Employment, Equity Ownership. Opalinska:GlaxoSmithKline: Employment, Equity Ownership. Nelson:GlaxoSmithKline: Equity Ownership. Stafkey-Mailey:Xcenda: Employment.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3313-3313 ◽  
Author(s):  
Asher A. Chanan-Khan ◽  
Suzanne Lentzsch ◽  
Hang Quach ◽  
Noemi Horvath ◽  
Marcelo Capra ◽  
...  

Abstract Introduction: Daratumumab is a human CD38 IgGκ monoclonal antibody that demonstrated significant activity and a manageable safety profile in combination with bortezomib and dexamethasone. In a randomized phase 3 study, daratumumab in combination with bortezomib and dexamethasone (DVd) significantly prolonged progression-free survival (PFS) versus bortezomib and dexamethasone alone (Vd) in a pre-specified interim analysis of patients (pts) with relapsed or refractory multiple myeloma (RRMM; Palumbo A. N Engl J Med 2016; in press). Herein, we examine subgroups from this study to compare the efficacy of DVd vs Vd in bortezomib-naive and bortezomib-experienced pt populations. In addition, the efficacy of DVd vs Vd in pts who were refractory to lenalidomide at last prior line of therapy was also evaluated. Methods: Pts who received ≥1 prior line of therapy were randomized (1:1) to 8 cycles (q3w) of Vd (bortezomib: 1.3 mg/m2 SC on Days 1, 4, 8, 11; dexamethasone: 20 mg PO on Days 1, 2, 4, 5, 8, 9, 11, 12) with or without daratumumab (16 mg/kg IV qw in Cycles 1-3, Day 1 of Cycles 4-8, then q4w until progression). Pts who were refractory to bortezomib were not eligible. The primary endpoint was PFS. Bone marrow aspirate samples that had been prepared with Ficoll were evaluated for minimal residual disease (MRD) using three different thresholds (10-4, 10-5, and 10-6) based on the ClonoSEQ assay (Adaptive Biotechnologies, Seattle, WA, USA). Results: Median follow-up was 7.4 months. Among bortezomib-naive pts (DVd, n=89; Vd, n=83), PFS was significantly improved with DVd vs Vd (median: not reached [NR] vs 7.5 months; HR, 0.25; 95% CI, 0.13-0.47; P&lt;0.0001); estimated 12-month PFS rates were 72% vs 28%, respectively. ORR was 88% with DVd vs 70% with Vd (P=0.0040), with ≥very good partial response (VGPR) rates of 72% vs 42% (P&lt;0.0001), and ≥complete response (CR) rates of 30% vs 20% (P=0.1199), respectively. For pts who previously received a bortezomib-containing regimen (DVd, n=162; Vd, n=164), PFS was also significantly longer with DVd vs Vd (median: 12.3 vs 6.7 months; HR, 0.46; 95% CI, 0.32-0.66; P&lt;0.0001). Estimated 12-month PFS rates were 55% vs 27%, respectively. ORR was significantly higher with DVd vs Vd (80% vs 60%; P=0.0001), along with significantly higher rates of ≥VGPR (52% vs 22%; P&lt;0.0001) and ≥CR (13% vs 3%; P=0.0019). Among pts who were refractory to lenalidomide at the last prior line of therapy (DVd, n=45; Vd, n=60), PFS was significantly longer in DVd vs Vd (median: 10.3 vs 4.4 mo; HR, 0.37; 95% CI, 0.21-0.65; P=0.0004; Figure). Within this subgroup, ORR was significantly higher for DVd vs Vd (81% vs 50%; P=0.0021), and the same trends were observed for rates of ≥VGPR (54% vs 12%; P&lt;0.0001) and ≥CR (20% vs 5%; P=0.0261). Updated efficacy and safety data, including MRD analyses across different sensitivity thresholds (10-4, 10-5, and 10-6), will be presented at the meeting. Conclusions: These analyses confirm that addition of daratumumab to Vd significantly improves outcomes for RRMM pts regardless of prior treatment with bortezomib. Importantly, this treatment benefit of DVd vs Vd was maintained in pts who were refractory to lenalidomide at the last prior line of therapy. These data lend further support to adding daratumumab to a standard-of-care regimen in RRMM. Figure Progression-free Survival in Patients Refractory to Lenalidomide at the Last Prior Line of Therapy Figure. Progression-free Survival in Patients Refractory to Lenalidomide at the Last Prior Line of Therapy Disclosures Lentzsch: BMS: Consultancy; Foundation One: Consultancy; Celgene: Consultancy, Honoraria. Quach:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Ovilla:Janssen: Consultancy. Qi:Janssen: Employment. Deraedt:Janssen: Employment, Equity Ownership. Schecter:Janssen: Employment, Equity Ownership. Amin:Janssen: Employment. Qin:Janssen: Employment. Casneuf:Johnson & Johnson: Equity Ownership; Janssen R&D, Beerse, Belgium: Employment. Chiu:Janssen: Employment. Sasser:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals R&D: Employment. Sonneveld:Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.


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