PHASE 2 STUDY OF DARATUMUMAB MONOTHERAPY IN PATIENTS WITH ?3 LINES OF PRIOR THERAPY OR DOUBLE REFRACTORY MULTIPLE MYELOMA: 54767414MMY2002 (SIRIUS)
Author(s): ,
Sagar Lonial
Affiliations:
Department of Hematology and Medical Oncology,Winship Cancer Institute, Emory University,Atlanta, GA,United States
,
Brendan Weiss
Affiliations:
Division of Hematology & Oncology, Department of Medicine,Abramson Cancer Center and Perelman School of Medicine, University of Pennsylvania,Philadelphia, PA,United States
,
Saad Usmani
Affiliations:
Levine Cancer Institute/Carolinas Healthcare System,Charlotte, NC,United States
,
Seema Singhal
Affiliations:
Robert H. Lurie Comprehensive Cancer Center, Division of Hem./Onc.,Northwestern University Feinberg School of Medicine,Chicago, IL,United States
,
Ajai Chari
Affiliations:
Tisch Cancer Institute, Mount Sinai School of Medicine,New York, NY,United States
,
Nizar Bahlis
Affiliations:
Tom Baker Cancer Center - University of Calgary,Calgary, AB,Canada
,
Andrew Belch
Affiliations:
Cross Cancer Institute,Edmonton, AB,Canada
,
Amrita Krishnan
Affiliations:
Department Hematology and Hematopoietic Stem Cell Transplant,City of Hope,Duarte, CA,United States
,
Robert Vescio
Affiliations:
Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute,Los Angeles, CA,United States
,
Maria Victoria Mateos
Affiliations:
University Hospital of Salamanca/IBSAL,Salamanca,Spain
,
Amitabha Mazumder
Affiliations:
NYU Perlmutter Cancer Center,New York, NY,United States
,
Robert Z Orlowski
Affiliations:
Department of Lymphoma/Myeloma,The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Heather Sutherland
Affiliations:
Leukemia/Bone Marrow Transplant Program, University of British Columbia,Vancouver, BC,Canada
,
Joan Blade
Affiliations:
IDIBAPS, Hospital Clinic de Barcelona,Barcelona,Spain
,
Emma C Scott
Affiliations:
Knight Cancer Institute, Oregon Health and Science University,Portland, OR,United States
,
Albert Oriol
Affiliations:
Institut Català d’Oncologia, Hospital Germans Trias i Pujol,Barcelona,Spain
,
Jesus Berjeda
Affiliations:
Sarah Cannon Research Institute,Nashville TN,United States
,
Mecide Gharibo
Affiliations:
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School Rutgers, The State University of New Jersey,New Brunswick, NJ,United States
,
Don A Stevens
Affiliations:
Norton Health Care,Louisville, KY,United States
,
Richard Le Blanc
Affiliations:
Hôpital Maisonneuve-Rosemont,Montreal, Quebec,Canada
,
Michael Sebag
Affiliations:
Royal Victoria Hospital,Montreal, Quebec,Canada
,
Natalie Callander
Affiliations:
University of Wisconsin Medical School,Madison, WI,United States
,
Andrzej Jakubowiak
Affiliations:
University of Chicago Medicine,Chicago, IL,United States
,
Darrell White
Affiliations:
Dalhousie University and QEII Health Sciences Ctr,Halifax, NS,Canada
,
Javier de la Rubia
Affiliations:
Hospital Dr Peset and Universidad Católica 'San Vicente Mártir',Valencia,Spain
,
Steen Lisby
Affiliations:
Genmab A/S,Copenhagen,Denmark
,
Huaibao Feng
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Imran Khan
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Clarissa Uhlar
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
Tahamtan Ahmadi
Affiliations:
Janssen Research & Development,Spring House, PA,United States
Peter Voorhees
Affiliations:
Division of Hematology/Oncology,Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill,Chapel Hill, NC,United States
EHA Learning Center. LONIAL S. Jun 13, 2015; 103136
Disclosure(s): Winship Cancer Institute, Emory University
Department of Hematology and Medical Oncology
Prof. Sagar LONIAL
Prof. Sagar LONIAL

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Abstract
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Abstract: S430

Type: Oral Presentation

Presentation during EHA20: From 13.06.2015 12:30 to 13.06.2015 12:45

Location: Room A2+3

Background
Novel agents including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs) have provided improved treatment outcomes for patients with multiple myeloma (MM). The majority of patients with MM still unfortunately relapse, with very limited options after PI and IMiD-based treatment.  Daratumumab (DARA) is a human anti-CD38 IgG1κ mAb and has previously shown single agent activity and good tolerability in relapsed/refractory MM (Lokhorst HM et al. ASCO 2014).

Aims
This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥3 prior lines of therapy including a PI and an IMiD, or double refractory to a PI and IMiD. Preliminary results are reported.

Methods
MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw for 8 weeks, q2w for 16 weeks, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC).

Results
Data for the 16 mg/kg DARA group are presented (n = 106). The median time from diagnosis was 4.8 years and patients received a median of 5 prior treatment lines. A total of 80% of patients received prior autologous stem cell transplants. Seventy five percent of patients were ISS stage 2 or higher. Ninety-six percent of patients were refractory to their last line of therapy and 95% were refractory to their last PI and IMiD. The proportions of patients refractory to other to agents included pomalidomide (63%), carfilzomib (48%) and alkylating agents (78%). Adverse events (AE; ≥20%) included fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during the first infusion with 4.7% of patients with grade 3 IRRs. No grade 4 IRRs were reported and no patients discontinued the study due to IRRs. Five patients (4.7%) discontinued treatment due to AEs and none of these AEs were assessed by the investigator to be DARA-related. The ORR (IRC assessed) was 29.2%, with 3 stringent complete responses, 10 very good partial responses, and 18 partial responses.  The ORR was consistent across clinically relevant subgroups. The median duration of response was 7.4 months.  The median time to progression was 3.7 months. Median overall survival (OS) has not been reached and the estimated 1-year OS rate is 65%.  After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy.

Summary
In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile.

Keyword(s): Multiple myeloma

Session topic: Multiple myeloma: Clinical studies 2
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