FDA Expands Daratumumab’s Indication to Frontline Myeloma Treatment

The U.S. Food and Drug Administration (FDA) approved a new indication for the anti-CD38 monoclonal antibody daratumumab, to include the treatment of patients who are newly diagnosed with myeloma and ineligible for autologous hematopoietic cell transplantation.

In the frontline setting, daratumumab is indicated for combination treatment with bortezomib, melphalan, and prednisone (VMP). This is the fifth indication for daratumumab, which is already approved for the treatment of patients with relapsed or refractory myeloma.

The decision was supported by data from the randomized, open-label, multicenter phase III ALCYONE trial, which was presented as a late-breaking abstract at the 2017 ASH Annual Meeting. In the trial, treatment with the daratumumab combination reduced the risk of disease progression or death by 50 percent, compared to treatment with VMP alone (hazard ratio [HR] = 0.50; 95% CI 0.38- 0.65; p<0.001). The median progressionfree survival (PFS) for the daratumumab combination was not reached, while PFS in the VMP-alone arm was 18.1 months (p value not provided).

In the ALCYONE trial, the most frequent AEs (>20%) in the daratumumab arm included upper respiratory–tract infection (48% vs. 28% in the VMP-alone arm), infusion reactions (28% vs. 0%), and peripheral edema (21% vs. 14%).

Source: Janssen press release, May 8, 2018; Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378:518-28.