ALCYONE: Daratumumab combo prolongs survival in multiple myeloma
A treatment regimen combining daratumumab plus bortezomib, melphalan and prednisone (VMP) markedly extends progression-free survival (PFS) in patients with multiple myeloma, inducing deep responses and demonstrating acceptable tolerability regardless of baseline renal function, according to the results of the phase III ALCYONE study.
ALCYONE included 706 patients ineligible for high-dose chemotherapy with autologous stem cell transplantation, and they were randomized to receive nine cycles of VMP either alone (control arm; n=356) or with daratumumab (n=350) until disease progression. At baseline, 295 had moderate renal impairment (creatinine clearance [CrCl] ≤60 mL/min; n=150 daratumumab; n=145 control) while 411 did not (CrCl >60 mL/min; n=200 daratumumab; n=211 control).
During a median 16.5 months of follow-up, the primary endpoint of PFS was longer in the daratumumab vs the control arm in both renal function subgroups (≤60 mL/min: median PFS, not reached [NR] vs 16.9 months; >60 mL/min: median PFS, NR vs 18.3 months). The combination of daratumumab plus VMP reduced the risk of disease progression or death by more than 60 percent in patients with moderately impaired renal function (hazard ratio [HR], 0.36; 95 percent CI, 0.24–0.56) and by about 40 percent in those without such impairment (HR, 0.63; 0.45–0.88). [EHA 2018, abstract PF583]
The daratumumab arm maintained its superiority over the control arm in terms of overall response rate (≤60 mL/min subgroup: 89 percent vs 73 percent; >60 mL/min subgroup: 92 percent vs 74 percent), complete response rate (≤60 mL/min: 43 percent vs 24 percent; >60 mL/min: 43 percent vs 25 percent) and minimal residual disease-negative rate (≤60 mL/min: 25 percent vs 8 percent; >60 mL/min 20 percent vs 5 percent).
Incidence of treatment-emergent adverse events (TEAEs) was similar between the daratumumab and control arms across the ≤60 mL/min (81 percent vs 82 percent, respectively) and >60 mL/min subgroups (75 percent vs 74 percent) and the overall population (78 percent vs 77 percent). Commonly reported grade 3–4 TEAEs included neutropaenia, thrombocytopaenia, anaemia and pneumonia. Likewise, rates of TEAEs of interest such as peripheral sensory neuropathy and infections did not significantly differ.
Finally, infusion-related reactions were seen in 27 percent of patients in the ≤60 mL/min subgroup and 29 percent in the >60 mL/min subgroup.
The present data show that the combination of daratumumab plus VMB provides significant clinical benefits compared with VMB alone in the treatment of patients with newly diagnosed multiple myeloma, researchers said.
More importantly, moderate renal impairment does not alter the potency of the regimen, they added.