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1852 Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM) Patients: An Update of Overall Survival in Castor

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 9, 2017, 5:30 PM-7:30 PM
Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Suzanne Lentzsch, MD, PhD1, Hang Quach, MBBS, MD2, Asher A. Chanan-Khan, MD3, Noemi Horvath, FRACP4, Marcelo Capra, MD, PhD5, Roberto Ovilla, MD6, Jae-Cheol Jo, MD7*, Ho-Jin Shin, MD8*, Piruntha Thiyagarajah, MBBS, BSc9, Himal Amin10*, Tineke Casneuf, PhD11*, Pieter Sonneveld, MD, PhD12, Jordan Schecter10* and Vania T M Hungria, MD, PhD13

1Columbia University Medical Center, New York, NY
2Peter MacCallum Cancer Centre & St. Vincent's Hospital, Melbourne, Australia
3Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL
4Department of Haematology, Royal Adelaide Hospital, SA Pathology, Adelaide, Australia
5Instituto do Cancer COR Hospital Mae de Deus, Porto Alegre, Bouvet Island
6Hospital Angeles Lomas, Huixquilucan, Mexico
7Ulsan University Hospital, Ulsan, Korea, Republic of (South)
8Pusan National University Hospital, Busan, Korea, Republic of (South)
9Janssen Research & Development, LLC, High Wycombe, United Kingdom
10Janssen Research & Development, LLC, Raritan, NJ
11Janssen Research & Development, LLC, Beerse, Belgium
12Department of Hematology, Erasmus Medical Center, Rotterdam, Netherlands
13Irmandade Da Santa Casa De Misericordia De São Paulo, São Paulo, Brazil

Introduction: Daratumumab (D) is a human monoclonal antibody targeting CD38 that is approved as monotherapy and in combination with immunomodulatory drugs (lenalidomide or pomalidomide) or a proteasome inhibitor (bortezomib) for RRMM. The combination of D and bortezomib plus dexamethasone (DVd) was compared to Vd in CASTOR (ClinicalTrials.gov NCT02136134), a randomized, multicenter, phase 3 study in patients with RRMM. In the primary analysis, 29 deaths in DVd and 36 deaths in Vd were observed (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.47-1.26; Palumbo et al, N Engl J Med 2016;375(8):754-66). Here, we provide an updated analysis of overall survival (OS) in CASTOR.

Methods: Eligible patients received ≥1 prior line of therapy and were randomly assigned to receive 8 cycles (every 3 weeks) of Vd (V 1.3 mg/m2 subcutaneously on Days 1, 4, 8, and 11; d 20 mg orally or intravenously (IV) on Days 1-2, 4-5, 8-9, and 11-12) with or without D (16 mg/kg IV once weekly in Cycles 1-3, every 3 weeks for Cycles 4-8, and every 4 weeks thereafter until disease progression). Patients who were refractory to bortezomib were ineligible. Progression-free survival (PFS) was the primary endpoint. OS was a secondary endpoint. Minimal residual disease (MRD) via next generation sequencing was assessed upon suspected complete response and at 6 and 12 months after the first dose at 3 sensitivity thresholds (10-4, 10-5, and 10-6) using the clonoSEQTM assay (Version 1.3, Adaptive Biotechnologies, Seattle, WA). A pre-specified interim analysis of OS was planned after 160 OS events had accrued.

Results: 251 patients received DVd and 247 patients received Vd. The median (range) age was 64.0 (30-88) years. Patients received a median of 2 (1-10) prior therapies; 61% received prior autologous stem cell transplant, 66% received prior bortezomib (with 13% receiving >1 prior bortezomib-containing regimen), 42% received prior lenalidomide, 48% received prior proteasome inhibitor plus immunomodulatory drug, 28% were refractory to lenalidomide, and 32% were refractory to their last line of therapy. The median duration of treatment with single-agent daratumumab after receiving 8 cycles of Vd was 11.9 months.

After median follow-up of 19.4 (range: 0-27.7) months, median OS has not been reached in either treatment group in the intent-to-treat (ITT) population (Figure 1A) and in patients who received 1 prior line of therapy (Figure 1B). An exploratory analysis of the number of OS events and the 24-month OS rates revealed fewer deaths with DVd vs Vd in the ITT population and in subgroups based on the number of prior lines of therapy (Table). Among MRD-negative patients at the 10–5 sensitivity threshold, no OS events occurred in patients receiving DVd (n=29) versus 1 OS event being reported in the Vd arm (n=6). Among patients previously treated with bortezomib, the 24-month OS rate was 68% with DVd (n=162) vs 52% with Vd (n=164). Among patients refractory to lenalidomide, the 24-month OS rate was 62% and 47% with DVd (n=60) and Vd (n=81), respectively.

Conclusions: Updated OS data and additional subgroup analyses will be presented at the meeting based on a pre-specified analysis of OS after 160 OS events.

Disclosures: Lentzsch: British-Myers Squibb, Celgene, Janssen: Consultancy; Takeda: Speakers Bureau; Caelum BioSciences: Equity Ownership. Quach: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Capra: Janssen: Speakers Bureau. Ovilla: Takeda Pharmaceutical Company: Consultancy, Honoraria. Thiyagarajah: Janssen: Employment. Amin: Janssen: Employment. Casneuf: Janssen: Employment. Sonneveld: Celgene Corporation, Amgen, Janssen, Karyopharm, SkylineDx, PharmaMar: Consultancy; Celgene, Amgen, Janssen, Karyopharm, Takeda: Consultancy, Honoraria, Research Funding; Celgene Corporation, Amgen, Janssen, Karyopharm, PharmaMar, SkylineDx: Honoraria. Schecter: Janssen: Employment. Hungria: Celgene, Roche, Takeda, Janssen, Amgen: Honoraria.

*signifies non-member of ASH