Lenalidomide (L) in Combination with Dexamethasone (D) Significantly Improves Time to Progression (TTP) in Non-Stem Cell Transplant Patients (pts) with Relapsed or Refractory (rel/ref) Multiple Myeloma (MM): Analysis from MM-009 and MM-010 Randomized Phase III Clinical Trials.

Abstract INTRODUCTION: Although autologous stem cell transplant (ASCT) has demonstrated high overall survival (OS) and progression free survival (PFS) in MM pts, for many pts this may not be an option due to comorbid conditions, advance age, aggressive refractory disease or personal preferences. Two phase III studies demonstrated superiority of the LD combination over D alone in rel/ref MM pts resulting in approval of L by the FDA. To evaluate the utility of LD combination in non-transplant pts we examined all pts who were enrolled on the MM-090 and MM-010 clinical trials and compared the efficacy and safety profile of LD combination among pts with no prior ASCT (NT) vs. those who had a prior ASCT (PT). METHODS: Data set from the 2 phase III trial was queried and pts with or without a previous ASCT identified. Clinical outcome (overall response rate, ORR; time to progression, TTP; overall survival, OS) was compared between the two groups. RESULTS: Of the 704 pts enrolled 353 (210 in the PT and 143 in the NT group) were randomized to receive LD. Patients demographic are summarized in Table 1. The median dose for L in both group was 25mg. Using the Blade criteria the ORR and CR rates in the PT vs. NT group were 63% (CR =13%) and 55% (CR=16%) p=0.12, while the median TTP was 44.1 and 61.4 (p=0.13), respectively. Toxicity: Although a higher incidence grade 3/4 neutropenia in the PT vs. NT group (38.1% vs. 27.3, p<.05) was noted the incidence of grade 3/4 thrombocytopenia were comparable (5.7% vs. 6.3%). The incidence for toxicity associated discontinuation of therapy in each arm was 12.9% and 19.6%. CONCLUSION: Our analysis showed no difference in ORR and CR rates in the 2 groups though there was a trend towards prolong TTP in NT pts. Although there was a slightly higher incidence of grade 3/4 neutropenia, overall there was no impact of prior ASCT on treatment outcome with LD. An interesting observation was that the median time from first pathologic diagnosis was the same for both groups; this observation is encouraging as they offer advantage to pts who may not have a chance to benefit from ASCT and supports the rationale to investigate L based therapies early on in the course of treatment. Characteristics of patients treated with LD combination. Prior Transplant Group (PT) No Prior Transplant (NPT) P value Median age (range) 59.5 (33–77) 69 (38–86) <0.001 Sex (%) M/F 62.4/37.6 55.2/44.8 0.187 Stage III (%) 60 70.6 0.184 B2M 3.1 4.1 <0.05 Time from first pathologic diagnosis in years (range) 3.4 (0.6–15.7) 2.9 (0.4–14.7) 0.098