ASCO 2015: First-in-Class Targeted Drug Daratumumab Is Effective as Single Agent in Heavily Treated Multiple Myeloma


Key Points

  • In a phase II trial of the anti-CD38 antibody daratumumab among 106 patients whose disease had progressed after at least three prior treatments, the overall response rate was 29.2%.
  • Responses were durable, with a median duration of 7.4 months.  
  • The estimated 1-year overall survival rate was 65%.

“Daratumumab monotherapy produced unprecedented overall responses that deepened over time” in a phase II trial among patients with heavily treated multiple myeloma, study author Saad Zafar Usmani, MD, reported at a press conference at the 2015 ASCO Annual Meeting. Dr. Usmani, a hematologist at Levine Cancer Institute/Carolinas Healthcare System in Charlotte, North Carolina, will present detailed study results at an oral abstract session on lymphoma and plasma cell disorders on Tuesday, June 2 (Abstract LBA8512).

In a group of 106 patients whose disease had progressed after at least three prior treatments, with a median of five, the overall response rate was 29.2%. The median duration of response was 7.4 months, and the 1-year overall survival rate was 65%.

First-in-Class Antibody

Daratumumab is a first-in-class antibody targeting CD38, which is highly expressed on multiple myeloma cells, and inducing cell death through multiple mechanisms. “CD38 is certainly an important new target in multiple myeloma,” commented ASCO spokesperson and press briefing moderator Charles J. Ryan, MD. Dr. Ryan is Professor of Clinical Medicine and Urology at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, and Leader of the Genitourinary Medical Oncology Program.

The study evaluated daratumumab monotherapy in the FDA Breakthrough Therapy designation population of patients with multiple myeloma who had received three or more lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who were double refractory to both. This is the largest study to show impressive activity of a monoclonal antibody as a stand-alone therapy for treatment-resistant multiple myeloma.

Infusion Reactions Generally Well Managed

Patients were initially randomly assigned to one of two dosing schedules, with 18 patients receiving daratumumab at 8 mg/kg and 16 patients receiving daratumumab at 16 mg/kg, but “the 16-mg/kg dose was found to be more efficacious,” Dr. Usmani said, and an additional 90 patients were enrolled at the 16-mg/kg dosing schedule. 

“The 16 mg/kg was well tolerated,” Dr. Usmani noted. No patients discontinued treatment due to treatment-related adverse events. Infusion-related reactions occurred among 42.5% of patients. These reactions “generally occurred during the first or the second infusion, were grade 1 or 2, and were managed with standard of care therapy,” Dr. Usmani said.

Less common side effects included fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), and cough (20.8%).

“These results highlight the potential of daratumumab as a novel, well-tolerated single-agent therapy in various stages of myeloma treatment,” Dr. Usmani concluded. “These data support further studies of daratumumab with current available/approved therapies.”

This study received funding from Janssen Research & Development. Dr. Usmani reported consulting or advisory roles with Celgene, Onyx, Millennium, and Sanofi; speakers’ bureau with Onyx, Celgene, and Millennium; research funding from Celgene, Millennium, Onyx, Array BioPharma, Janssen Oncology, Pharmacyclics, and Sanofi. For full disclosures of the study authors, view the study abstract at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.