Randomized Phase 3 study of pomalidomide cyclophosphamide dexamethasone versus pomalidomide dexamethasone in relapse or refractory myeloma: an Asian Myeloma Network study (AMN003).

Pomalidomide has been shown to improve survival in patients with relapsed/refractory myeloma (RRMM). However, the optimal pomalidomide-based combinations in RRMM are not known. This study compared pomalidomide, cyclophosphamide, dexamethasone (PCD) with pomalidomide and dexamethasone (PD) in Asian patients with RRMM. Patients were randomly assigned to receive PCD or PD. Patients received pomalidomide at 4 mg from days 1 to 21, dexamethasone at 40 mg once a week, and those in the PCD arm received cyclophosphamide at 400 mg once weekly for three weeks. The primary endpoint was progression-free survival. One hundred and twenty-two patients were randomized (62 PCD, 60 PD). Baseline characteristics were comparable between both arms. The median prior lines of therapy were three. At a median follow-up of 13.5 (median range 9-18) months, median progression free survival was significantly longer at 10.9 months (95% confidence interval 7.1-27.7) in the PCD group compared with 5.8 months (95% CI, 4.4-6.9) in the PD group (hazard ratio 0.43; p < 0.001). Adverse events rates were similar in both arms. The most common grade ≥3 adverse events were hematological toxicities and pneumonia. 34 deaths occurred during the study (PCD: 17; PD: 17) and three were deemed to be related to study treatment. In Asian patients with RRMM after exposure to proteasome inhibitor and lenalidomide, progression-free survival was significantly prolonged with the addition of cyclophosphamide to PD, with a manageable safety profile.Trial ID: Registered at www.clinicaltrials.gov : NCT03143049.