Lenalidomide versus lenalidomide + dexamethasone prolonged treatment after second-line lenalidomide + dexamethasone induction in multiple myeloma

Abstract

Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2 years in the phase 2 trial were 47% versus 31% for Len versus Len+Dex (P = 0.14). After 36 months median follow-up in surviving patients, median time to progression was not reached with Len+Dex and was 24.9 months (95% confidence interval 12.5-not calculable, P < 0.001) with Len. Three-year OS among the total observational study population was 61% (95% CI, 52-69%). The corresponding rate among patients who entered the phase 2 clinical trial was 73% (95% CI, 60-83%) and was significantly lower among those patients who achieved ≥PR but did not proceed into the phase 2 trial (55%; P = 0.01). In the phase 2 trial, OS was 73% in both treatment arms (P = 0.70). Neutropenia and thrombocytopenia were more common with prolonged (phase 2 trial) versus short-term (observational study) Len administration but remained manageable. Prolonged treatment with Len with or without Dex provides sustained, clinically relevant responses and demonstrates an acceptable safety profile.

Keywords: Clinical Trial; Lenalidomide; Multiple Myeloma.

Figure 1

Outcomes in the total observational study population (N = 133). (A) TTP measured from the time of inclusion in the study at first relapse. (B) OS measured from the time of inclusion in the study.

Figure 2

Outcomes in patients treated with Len (n = 31) versus Len+Dex (n = 31) in the phase 2 clinical trial. (A) TTP measured from randomization. Disease progression in the Len versus the Len+Dex arm was 47% (31–66%) versus 31% (17–52%) at 2 years, and 55% (38–74%) versus 38% (22–61%) at 3 years (P = 0.14). (B) OS measured from randomization. Three‐year OS was 73% in both treatment arms (95% CI 53–86% for Len+Dex, 53–85% for Len; P = 0.70).

Figure 3

Results from the EORTC quality of life questionnaires, presented as mean and 95% confidence intervals. (A) Results from the core module, EORTC QLQ‐C30. (i) physical functioning (PF2), role functioning (RF2), emotional functioning (EF), cognitive functioning (CF); (ii) social functioning (SF), global health (QL2), fatigue (FA), pain (PA); (iii) nausea and vomiting (NV), dyspnoea (DY), insomnia (SL), appetite loss (AP); (iv) constipation (CO), diarrhea (DI), and financial difficulties (FI). (B) Results from the multiple myeloma module, EORTC QLQ‐MY20: future perspective (MYFP), body image (MYBI), disease symptoms (MYDS), and side effects of treatment (MYSE). BL indicates baseline (n = 105); 3 m, at 3 months of treatment (n = 61); 6 m, at 6 months of treatment (n = 22); EoT, end of trial (1 month after the ninth cycle; n = 38).