SIRIUS supports single-agent daratumumab in refractory multiple myeloma

Jan 19 2016

By Shreeya Nanda, Senior medwireNews Reporter

Phase II trial results show that daratumumab monotherapy elicits responses and has a favourable adverse event profile in heavily-pretreated, refractory multiple myeloma patients.

On the basis of these findings, the anti-CD38 agent has been approved by the US FDA for the treatment of refractory disease, say the authors.

The primary analysis of the ongoing SIRIUS trial included 106 patients who had received a median of five prior lines of therapy. Ninety-five percent of patients were refractory to proteasome inhibitors and immunomodulatory drugs and 80% had received autologous stem cell transplantation.

Participants received open-label daratumumab at a dose of 16 mg/kg weekly for the initial 8 weeks, followed by treatment at 2-week intervals for 16 weeks and at 4-week intervals thereafter.

After a median follow-up of 9.3 months, an overall response was observed in 29.2% of patients, with 2.8% of patients achieving a stringent complete response, 9.4% a very good partial response and 17.0% a partial response.

The median time to initial response and median duration of response were 1.0 and 7.4 months, respectively, report Sagar Lonial (Emory University, Atlanta, Georgia, USA) and co-workers.

At the time of this analysis, progression-free survival was a median of 3.7 months and median overall survival was not reached, although at a later cutoff, the latter was estimated at 17.5 months.

Altogether 23% of study participants experienced a treatment-emergent side effect of grade 3 or 4, with anaemia (24%), thrombocytopenia (19%) and neutropenia (12%) occurring most frequently.

However, no patient discontinued treatment as a result of drug-related adverse events, and the overall toxicity profile was favourable, making daratumumab “an attractive drug for use in combination regiments”, the researchers write in The Lancet.

Commentator S Vincent Rajkumar (Mayo Clinic, Rochester, Minnesota, USA) agrees and believes that daratumumab will not only be added to active triplet combinations for refractory disease, but will also be evaluated in the front-line setting in patients with newly diagnosed disease and perhaps even in those with smouldering disease.

However, the efficacy of daratumumab across the various cytogenetic subtypes of the disease and its long-term effects are unknown at present, he cautions.

Rajkumar also points out that “[i]t will be important to see how daratumumab can be used in the optimum manner with another monoclonal antibody, elotuzumab (targeting SLAMF7), which was approved in the USA within weeks of the approval of daratumumab.”

Nevertheless, the commentator concludes: “The progress in this disease is astonishing; there is no hype here.”

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