Daratumumab May Be ‘Effective Option’ For Refractory Multiple Myeloma

Positive daratumumab phase II efficacy and safety profile results for patients with heavily pretreated multiple myeloma

medwireNews: Phase II SIRIUS trial findings add support to the use of the CD38-targeted monoclonal antibody daratumumab in patients with refractory multiple myeloma.

“[D]aratumumab seems to be an effective option for patients with relapsed and refractory multiple myeloma for whom available treatments have been exhausted”, say Sagar Lonial, from Emory University in Atlanta, Georgia, USA, and co-investigators.

The researchers report results in The Lancet for 106 patients recruited to the ongoing open-label study who were given a dose of 16 mg/kg per week for 8 weeks, followed by treatment at 2-week intervals for 16 weeks and 4-week cycles thereafter.

The patients had received a minimum of three and a median of five prior therapies and 95% were refractory to proteasome inhibitors and immunomodulatory drugs. Eighty percent of the patients had previously undergone autologous stem cell transplantation.

At the primary analysis, 7.7 months after the last patient received a first dose, 29.9% of patients achieved an overall response, with 2.8% achieving a stringent complete response, 9.4% a very good partial response and 17.0% a partial response.

Response occurred a median of 1.0 month after treatment and lasted for a median of 7.4 months. Progression-free survival was a median of 3.7 months, and at a second safety update analysis, median overall survival was 17.5 months.

Fatigue was reported by 40% of patients and anaemia by 33% but the investigators say daratumumab was “well tolerated”, with none of the patients discontinuing treatment because of treatment-related side effects.

S. Vincent Rajkumar, from the Mayo Clinic in Rochester, Minnesota, USA, discusses the “striking” daratumumab findings in an accompanying comment, noting that the single-agent activity is higher than that of other treatments for multiple myeloma, despite being given to heavily pretreated patients, and that the agent has an “outstanding” safety profile.

He believes that daratumumab will, like rituximab in myeloma, be added to active triplet treatment combinations for refractory disease and be tested as a front-line treatment for newly diagnosed multiple myeloma, both as a maintenance treatment and as a therapy for those with smouldering disease.

Nevertheless, the commentator acknowledges that research is required to determine if daratumumab is effective across all cytogenetic subtypes of disease and if it has any long-term side effects.

“Finally, it is impossible to fathom how any health-care system can absorb the cost of a four-drug or five-drug combination in multiple myeloma if each new drug is priced at several thousand dollars per month”, he concludes.

“Clearly, new treatment strategies of intensive but more abbreviated courses of therapy, which produce long treatment-free intervals, improve quality of life, and hopefully cure the disease in at least a subset of patients, need to be developed.”


Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016; Advance online publication 6 January. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01120-4

Rajkumar SV. Daratumumab in multiple myeloma. Lancet 2016; Advance online publication 6 January. DOI: http://dx.doi.org/10.1016/S0140-6736(15)01226-X

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