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2747 Pomalidomide and Dexamethasone with or without Subcutaneous Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma: Updated Analysis of the Phase 3 Apollo Study

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
Clinical Trials, Biological therapies, Adults, Workforce, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy, Study Population
Sunday, December 12, 2021, 6:00 PM-8:00 PM

Pieter Sonneveld, MD1, Evangelos Terpos, MD, PhD2, Mario Boccadoro3, Sosana Delimpasi, MD4*, Meral Beksac, MD5, Eirini Katodritou, MD6*, Philippe Moreau, MD, PhD7*, Luca Baldini, MD, PhD8*, Argiris Symeonidis, MD, PhD9, Jelena Bila10*, Albert Oriol11*, Maria-Victoria Mateos12, Hermann Einsele13, Ioannis Orfanidis14*, Tobias Kampfenkel15, Yanping Qiu16*, Himal Amin17*, Michele Kosh18*, NamPhuong Tran19*, Robin Carson, MD, BA18 and Meletios A. Dimopoulos, MD2

1Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands
2National and Kapodistrian University of Athens, Athens, Greece
3University of Torino, Turin, Italy
4Hematology/Lymphomas and Bone Marrow Transplantation Unit, Evangelismos Hospital, Athens, Greece
5Ankara University School of Medicine Department of Hematology, Ankara, Turkey
6Theagenio Cancer Hospital, Thessaloniki, Greece
7University Hospital Hotel-Dieu, Nantes, France
8UO Ematologia, Fondazione IRCCS Cà Granda, OM Policlinico, Università degli Studi, Milan, Italy
9Hematology Division, Department of Internal Medicine, University of Patras, Patras, Greece
10University of Belgrade, Belgrade, Serbia
11Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain
12University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain
13Würzburg University Medical Centre, Würzburg, Germany
14Health Data Specialists S.A., Dublin, Ireland
15Janssen Research & Development, LLC, Leiden, Netherlands
16Janssen Research & Development, LLC, Beijing, China
17Janssen Research & Development, LLC, Raritan, NJ
18Janssen Research & Development, LLC, Spring House, PA
19Janssen Research & Development, LLC, Los Angeles, CA

Introduction: Daratumumab (DARA) is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. DARA is approved as monotherapy or in combination with standard-of-care regimens for the treatment of relapsed or refractory multiple myeloma (RRMM). In the primary analysis (median follow-up, 16.9 months) of the phase 3 APOLLO study (NCT03180736), the addition of DARA to pomalidomide and dexamethasone (D-Pd) showed a significant progression-free survival (PFS) improvement over pomalidomide and dexamethasone (Pd) alone in patients (pts) with RRMM (Dimopoulos MA, et al. Lancet Oncol. 2021;22[6]:801-812). Here, we report results from the APOLLO study, including outcomes of pts refractory to lenalidomide based on the last dose of lenalidomide received.

Methods: Eligible pts were ≥18 years of age, had RRMM, had received ≥1 prior line of therapy (including both a proteosome inhibitor and lenalidomide), and had responded to prior treatment; pts with only 1 prior line of therapy were required to be refractory to lenalidomide. Pts were randomized 1:1 to Pd ± DARA, stratified via International Staging System disease stage (I vs II vs III) and number of lines of prior therapy (1 vs 2-3 vs ≥4). All pts received 28-day cycles of pomalidomide (4 mg PO daily on Days 1-21) and dexamethasone (40 mg [20 mg for pts ≥75 years of age], PO daily on Days 1, 8, 15, and 22). Pts in the D-Pd group received DARA subcutaneously (DARA SC; 1,800 mg; co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc.]) or, prior to a protocol amendment, intravenously (DARA IV; 16 mg/kg; n=7) weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks thereafter. Pts receiving DARA IV were allowed to switch to DARA SC starting on Day 1 of Cycle 3 or later. All pts were treated until disease progression or unacceptable toxicity. The primary endpoint was PFS.

Results: In total, 304 pts were randomized (D-Pd, n=151; Pd, n=153). At the time of randomization, 120 (79.5%) pts in the D-Pd group and 122 (79.7%) pts in the Pd group were refractory to lenalidomide. Among pts refractory to lenalidomide, the last dose of lenalidomide received was 5-10 mg in 30 (25.0%) pts in the D-Pd group and 31 (25.4%) pts in the Pd group and was 15-25 mg in 86 (71.7%) pts in the D-Pd group and 89 (73.0%) pts in the Pd group. With a median follow-up of 16.9 months, the median PFS in the overall population was 12.4 months in the D-Pd group versus 6.9 months in the Pd group (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47-0.85; P=0.0018); the estimated 18-month PFS rate was 42.1% for the D-Pd group and 25.5% for the Pd group. Among pts refractory to lenalidomide, the median PFS was 9.9 months in the D-Pd group and 6.5 months in the Pd group (HR, 0.66; 95% CI, 0.49-0.90). For lenalidomide-refractory pts who last received a dose of 5-10 mg lenalidomide, the median PFS was 10.3 months for the D-Pd group and 8.5 months for the Pd group (HR, 0.75; 95% CI, 0.41-1.36); for lenalidomide-refractory pts who last received a dose of 15-25 mg lenalidomide, the median PFS was 10.7 months for the D-Pd group and 6.1 months for the Pd group (HR, 0.61; 95% CI, 0.42-0.88) (Figure). Grade 3/4 treatment-emergent adverse events occurred in 130 (87.3%) pts in the D-Pd group and 123 (82.0%) pts in the Pd group; the most frequently reported (≥15% in both groups) were neutropenia (67.8% vs 50.7%), thrombocytopenia (17.5% vs 18.0%), and anemia (16.8% vs 21.3%). Grade 3/4 pneumonia occurred in 20 (13.4%) pts in the D-Pd group and 10 (6.7%) of pts in the Pd group. Serious adverse events occurred in 75 (50.3%) pts in the D-Pd group and 59 (39.3%) pts in the Pd group.

Conclusion: The addition of DARA to Pd provided a PFS benefit in the overall pt population and among pts refractory to lenalidomide. The safety profile observed in the APOLLO trial was consistent with previous reports for DARA SC and Pd. Additional analyses for lenalidomide-refractory pts, as well as efficacy and safety data for the overall population at longer follow up, will be presented.

Disclosures: Sonneveld: Celgene/BMS: Consultancy, Honoraria, Research Funding; SkylineDx: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Terpos: Celgene: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Boccadoro: Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and AbbVie: Honoraria; Janssen and GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and Mundipharma: Research Funding. Delimpasi: Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Beksac: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Katodritou: GSK, Amgen, Karyopharm, Abbvie, Janssen-Cilag, Genesis Pharma, Sanofi: Honoraria, Research Funding. Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Oncopeptides: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Abbvie: Honoraria. Symeonidis: Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi/Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Demo: Research Funding; WinMedica: Research Funding; GenesisPharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bila: Janssen, Takeda, AMGEN: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Oriol: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/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; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mateos: Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: 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; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Bluebird bio: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria; Adaptive Biotechnologies: 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. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Orfanidis: Health Data Specialists: Current holder of individual stocks in a privately-held company. Kampfenkel: Janssen: Current Employment. Qiu: Janssen: Current Employment. Amin: Janssen: Current Employment, Current equity holder in publicly-traded company. Kosh: Janssen: Current Employment. Tran: Janssen: Current Employment, Current equity holder in publicly-traded company. Carson: Janssen: Current Employment. Dimopoulos: Beigene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria; BMS: Honoraria.

OffLabel Disclosure: The regimen is approved for patients who have received at least two prior therapies, whereas the APOLLO study included patients who have received at least 1 prior therapy.

*signifies non-member of ASH