AN OPEN-LABEL, RANDOMISED PHASE 3 STUDY OF DARATUMUMAB, LENALIDOMIDE, AND DEXAMETHASONE (DRD) VERSUS LENALIDOMIDE AND DEXAMETHASONE (RD) IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): POLLUX
Author(s): ,
Meletios A Dimopoulos
Affiliations:
National and Kapodistrian University of Athens,Athens,Greece
,
Albert Oriol
Affiliations:
Institut Català d’Oncologia, HGTiP,Barcelona,Spain
,
Hareth Nahi
Affiliations:
Karolinska Institute and the Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge,Stockholm,Sweden
,
Jesus San Miguel
Affiliations:
Clinica Universidad de Navarra, CIMA,Pamplona,Spain
,
Nizar J Bahlis
Affiliations:
Tom Baker Cancer Center, University of Calgary,Calgary, Alberta,Canada
,
Neil Rabin
Affiliations:
Department of Haematology, University College London Hospitals NHS Trust,London,United Kingdom
,
Robert Orlowski
Affiliations:
Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Mieczyslaw Komarnicki
Affiliations:
Department of Hematology and Stem Cell Transplantation, Poznan University of Medical Sciences,Poznan,Poland
,
Kenshi Suzuki
Affiliations:
Japanese Red Cross Medical Center, Department of Hematology,Tokyo,Japan
,
Torben Plesner
Affiliations:
Vejle Hospital and University of Southern Denmark,Vejle,Denmark
,
Olga S Samoilova
Affiliations:
Nizhny Novgorod Region Clinical Hospital,Nizhny Novgorod,Russian Federation
,
Sung-Soo Yoon
Affiliations:
Department of Internal Medicine, Seoul National University College of Medicine,Seoul,Korea, Republic Of
,
Dina Ben Yehuda
Affiliations:
Hematology Department, Hadassah-Hebrew University Medical Center,Jerusalem,Israel
,
Paul G Richardson
Affiliations:
Dana-Farber Cancer Institute, Harvard Medical School,Boston, MA,United States
,
Hartmut Goldschmidt
Affiliations:
University Hospital Heidelberg and German Cancer Research Center,Heidelberg,Germany
,
Donna Reece
Affiliations:
Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre,Toronto, Ontario,Canada
,
Nushmia Khokhar
Affiliations:
Janssen Research and Development,Spring House, PA,United States
,
Lisa O’Rourke
Affiliations:
Janssen Research and Development,Spring House, PA,United States
,
Christopher Chiu
Affiliations:
Janssen Research and Development,Spring House, PA,United States
,
Xiang Qin
Affiliations:
Janssen Research & Development,Horsham, PA,United States
,
Mary Guckert
Affiliations:
Janssen Research and Development,Spring House, PA,United States
,
Tahamtan Ahmadi
Affiliations:
Janssen Research and Development,Spring House, PA,United States
Philippe Moreau
Affiliations:
Hematology, University Hospital Hôtel-Dieu,Nantes,France
EHA Library. Dimopoulos M. Jun 10, 2016; 135349; LB2238 Topic: 3Ec Plasma cell myeloma (Multiple myeloma)
Disclosure(s): National and Kapodistrian University of Athens
Prof. Dr. Meletios A Dimopoulos
Prof. Dr. Meletios A Dimopoulos
Contributions
Abstract
Abstract: LB2238

Type: Presidential Symposium

Presentation during EHA21: On Friday, June 10, 2016 from 16:47 - 17:00

Location: Hall A1

Background
Daratumumab (D), a human anti-CD38 IgGκ monoclonal antibody, was associated with rapid, deep, and durable responses and a favorable safety profile when combined with lenalidomide and dexamethasone (Rd) in a phase 1/2 study of relapsed or relapsed and refractory multiple myeloma pts (Plesner T, et al. ASH 2015, Abs. 507).
Aims: To compare the efficacy and safety of D in combination with Rd vs Rd alone in pts with RRMM in a randomised, open-label, multicenter, phase 3 study (POLLUX; NCT02076009).

Aims
To compare the efficacy and safety of D in combination with Rd vs Rd alone in pts with RRMM in a randomised, open-label, multicenter, phase 3 study (POLLUX; NCT02076009).

Methods
Pts who received at least 1 prior line of therapy for myeloma were randomised (1:1) to R 25 mg orally on Days 1-21 of each 28-day cycle and d 40 mg weekly, with or without D (16 mg/kg qw for 8 weeks, q2w for 16 weeks, then q4w until progression). The primary endpoint is progression-free survival (PFS). Secondary endpoints are time to progression (TTP), overall response rate (ORR), rate of very good partial response (VGPR) or better, minimal residual disease–negative rate, overall survival (OS), duration of response, time to response, and safety.

Results
569 pts were randomised. Median age of pts was 65 years old. Pts received a median of 1 prior line of therapy (range 1-11), with 19% of pts with ≥3 prior lines of therapy. Eighty-six percent received a prior PI, and 55% received prior IMiD, including 18% prior R, with 44% having received both a PI and an IMiD; 27% were refractory to the last line of prior therapy, 18% were PI refractory, and none were R refractory. After a median follow-up of 13.5 months, D significantly improved median PFS (63% reduction in the risk of progression/death) for DRd vs Rd (Figure). Addition of D to Rd significantly delayed TTP vs Rd (not reached [NR] vs estimated median of 18.4 mo; hazard ratio, 0.34; 95% CI, 0.23-0.48; P<0.0001). D significantly increased ORR (93% vs 76%, P<0.0001) and rates of VGPR or better (76% vs 44%, P<0.0001) and complete response (CR) or better (43% vs 19%, P<0.0001) for DRd vs Rd, respectively. The median duration of response was NR for DRd vs 17.4 months for Rd. All preplanned sensitivity analyses were consistent with results from the primary analysis. Pre-specified subgroup analyses of PFS demonstrated that the treatment effect of DRd over Rd was consistent across all pre-specified subgroups. The most common (<25%) TEAEs (DRd/Rd) were neutropenia (59%/43%), diarrhea (43%/25%), fatigue (35%28%), upper respiratory tract infection (32%/21%), anemia (31%/35%), constipation (29%/25%), cough (29%/13%), thrombocytopenia (27%/27%), and muscle spasms (26%/19%). Most common grade 3/4 TEAEs (>10%) were neutropenia (52%/37%), thrombocytopenia (13%/14%), and anemia (12%/20%). The rate of Grade 3/4 infections/infestations was 28% in the DRd group and 23% in the Rd group and the most common Grade 3/4 infections/infestations TEAE (≥5%) was pneumonia (8%/8%). Similar rates of treatment discontinuation due to TEAEs were observed (7%/8%). D-associated infusion-related reactions (IRR; 48% of pts) mostly were grade 1/2 (grade 3/4, 5%/0%); most (92% of IRRs) occurred during the first infusion.

Summary/Conclusion
DRd was superior to Rd alone. A significant reduction in the risk of disease progression/death was demonstrated with DRd vs Rd. DRd induced deep and durable responses, including doubling stringent CR/CR rates and significantly increasing the rate of VGPR or better vs Rd alone. DRd was associated with a manageable safety profile consistent with the known safety profile of D and Rd. The combination of D and Rd potentially represents a new standard of care for pts with >1 prior treatment.



Session topic: Presidential Symposium

Keyword(s): Multiple myeloma

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