Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial.

Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23-65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was ⩽2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2 mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.

A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma.

Patients with asymptomatic (smoldering) multiple myeloma (AMM) have a high risk of transformation to active multiple myeloma (MM). Bisphosphonates such as zoledronic acid (ZLD) reduce skeletal events in MM and the immunomodulatory agent thalidomide (Thal) has proven effectiveness in active MM. We hypothesized that treatment with Thal and ZLD would prolong the time to progression (TTP) to MM over ZLD alone. Eligible patients had asymptomatic MM and all patients received ZLD 4 mg intravenous monthly; the treatment arm also received Thal 200 mg per day. The TTP was superior for Thal/ZLD (n=35) patients compared with ZLD alone (n=33); median TTP of 2.4 years (95% confidence interval (CI): 1.4-3.6) versus 1.2 years (95% CI: 0.7-2.5) (hazard ratio (HR), 2.05; 95% CI: 1.1-3.8; P-value: 0.02). At 1 year, 86% of Thal/ZLD patients were progression free compared with 55% on ZLD alone (P=0.0048). The overall response rate after year 1 was 37% for Thal/ZLD with a median duration of response of 3.3 years (95% CI: 1.1-NA); there were no confirmed responses to ZLD alone (P=0.0004). The addition of Thal to standard ZLD produces anti-tumor responses whereas ZLD alone does not. Thal/ZLD also prolongs TTP from AMM to MM. This study provides the rationale for further studies in patients with AMM to delay chemotherapy.