-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1151 Efficacy of Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Patients with 1 to 3 Prior Lines of Therapy: Updated Analysis of PolluxClinically Relevant Abstract

Myeloma: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma: Therapy, excluding Transplantation: Immunotherapy
Monday, December 5, 2016: 5:30 PM
Hall AB (San Diego Convention Center)

Saad Z Usmani, MD, FACP1, Meletios Dimopoulos2, Andrew Belch3, Darrell White, MD4, Lofti Benboubker5*, Gordon Cook, MD, PhD6, Merav Leiba, MD7*, James Morton, MBBS, BSc(Med), FRACP, FRCPA8*, P. Joy Ho9, Kihyun Kim10*, Naoki Takezako, MD, PhD11, Nushmia Z Khokhar12*, Mary Guckert12*, Kaida Wu, MD, PhD12, Xiang Qin12*, Tineke Casneuf13*, Christopher Chiu, PhD12*, A. Kate Sasser12* and Jesús F. San-Miguel14

1Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC
2National and Kapodistrian University of Athens, Athens, Greece
3Department of Oncology, University of Alberta Cross Cancer Institute, Edmonton, AB, Canada
4QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada
5Service d’Hématologie et Thérapie Cellulaire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours, France
6St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom
7Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
8Icon Cancer Care, South Brisbane, QLD, Australia
9Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
10Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, The Republic of
11Department of Hematology, National Hospital Organization Disaster Medical Center of Japan, Tachikawa, Japan
12Janssen Research & Development, LLC, Spring House, PA
13Janssen Research & Development, Beerse, Belgium
14Clínica Universidad de Navarra-CIMA, IDISNA, Pamplona, Spain

Introduction: Daratumumab is a human monoclonal antibody targeting CD38 that demonstrated superior efficacy in combination with lenalidomide and dexamethasone (DRd) versus lenalidomide and dexamethasone alone (Rd) in a pre-specified interim analysis of a randomized phase 3 study of relapsed or refractory multiple myeloma (RRMM; Dimopoulos MA, et al. N Engl J Med 2016; in press). We report subgroup analyses from this study in patients (pts) who received 1 to 3 prior lines of therapy (1-3 PL), including outcomes based on high-risk cytogenetics within these subgroups.

Methods: Patients (pts) who received ≥1 prior line of therapy were randomized (1:1) to Rd (lenalidomide: 25 mg PO on Days 1-21 of each 28-day cycle; dexamethasone: 40 mg PO weekly) with or without daratumumab (16 mg/kg IV qw for 8 weeks, q2w for 16 weeks, then q4w until progression). The primary endpoint was progression-free survival (PFS). The site investigator determined the number of prior lines of therapy according to IMWG consensus guidelines. Treatment-free interval (TFI) was defined as the duration between the end/start date of last line of prior therapy and the date of randomization. Pts with high-risk cytogenetic status had at least one of the following abnormalities as assessed via fluorescence in-situ hybridization or karyotyping by local laboratory assessment: t(4;14), t(14;16), or del17p.

Results: In the 1-3 PL subgroup (DRd, n=272; Rd, n=264), PFS was significantly improved with DRd vs Rd (median: not reached [NR] vs 18.4 months; HR, 0.36; 95% CI, 0.25-0.50; P<0.0001), with estimated 12-month PFS rates of 83.2% vs 60.4%, respectively. Time to progression was also significantly longer with DRd vs Rd (median: NR vs 18.4 months; HR, 0.32; 95% CI, 0.22-0.46; P<0.0001). ORR (94% vs 77%), rates of very good partial response (VGPR) or better (76% vs 45%) and complete response (CR) or better (44% vs 20%) were significantly higher with DRd vs Rd, respectively (P<0.0001 for all). Among responders, median time to VGPR or better was 2.8 months in DRd vs 2.9 months in Rd; median time to CR or better was 6.7 months vs 7.5 months, respectively. For pts in the 1-3 PL subgroup with high-risk cytogenetics (n=33 in each treatment group), significantly longer PFS was observed in DRd vs Rd (median: NR vs 8.3 months; HR, 0.30; 95% CI, 0.14-0.67; P=0.0019). Significantly higher ORR (91% vs 69%; P=0.0267), rate of VGPR or better (73% vs 28%; P=0.0004), and rate of CR or better (36% vs 9%; P=0.0104) were achieved in pts with high-risk cytogenetic status treated with DRd vs Rd, respectively.

For 1-3 PL pts who had a TFI of >12 months (DRd, n=138; Rd, n=145), median PFS was NR in DRd vs 18.4 months in Rd (HR, 0.42; 95% CI, 0.24-0.74; P=0.0019; Figure A); the estimated 12-month PFS rate was 88.0% vs 74.5%, respectively. ORR was significantly higher with DRd vs Rd (96% vs 86%, P=0.0084), along with rate of VGPR or better (77% vs 56%; P=0.0008) and rate of CR or better (43% vs 27%; P=0.0083). Among pts with a TFI of ≤12 months (DRd, n=134; Rd, n=119), median PFS was NR in DRd vs 10.3 months in Rd (HR, 0.32; 95% CI, 0.21-0.51; P<0.0001; Figure B); the estimated 12-month PFS rate was 78.1% vs 43.1%, respectively. ORR (92% vs 67%), rate of VGPR or better (76% vs 32%), and rate of CR or better (44% vs 10%) were all significantly higher with DRd vs Rd (P<0.0001 for all).

Among pts with 1-3 PL who were refractory to their last line of therapy (DRd, n=73; Rd, n=67), PFS was significantly prolonged with DRd vs Rd (median: NR vs 10.3 mo; HR, 0.42; 95% CI, 0.25-0.72; P=0.0010). ORR (92% vs 66%; P=0.0002), rate of VGPR or better (72% vs 34%; P<0.0001), and rate of CR or better (47% vs 14%; P<0.0001) were significantly higher with DRd vs Rd.

Data for all subgroup analyses will be updated for the meeting.

Conclusions: Responses with DRd were deep and durable which translated into significantly improved clinical outcomes vs Rd in 1-3 PL pts with RRMM. The results of these subgroup analyses suggest that the treatment benefit of DRd vs Rd was maintained across these subgroups, including pts with TFI of ≤12 months and those who were refractory to their last line of therapy.

Figure: Progression-free survival in patients with 1 to 3 prior lines of therapy and treatment-free interval of (A) >12 months (B) ≤12 months prior to randomization

 

Disclosures: Usmani: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Dimopoulos: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Honoraria; Genesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Belch: Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria. White: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria. Benboubker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cook: Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Glycomimetics: Consultancy. Ho: Amgen: 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; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Khokhar: Janssen: Employment. Guckert: Janssen: Employment; Johnson & Johnson: Equity Ownership. Wu: Janssen: Employment. Qin: Janssen: Employment. Casneuf: Johnson & Johnson: Equity Ownership; Janssen R&D, Beerse, Belgium: Employment. Chiu: Janssen: Employment. Sasser: Janssen: Employment; Johnson & Johnson: Equity Ownership. San-Miguel: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH