Lenalidomide Overcomes Poor Prognosis Conferred by Deletion of Chromosome 13 and t(4;14) in Multiple Myeloma: MM016 Trial.

Background: Deletion of chromosome 13 (del13) and t(4;14) in multiple myeloma (MM) predicts poor response and shortened survival. Combination of Lenalidomide and Dexamethasone (Len/Dex) in two large randomized trials demonstrated superior activity and outcomes in relapsed and refractory MM patients when compared to dexamethasone monotherapy. Here we report the efficacy (response rate RR and 6 mos event free survival EFS) of Lenalidomide in MM patients, according to their del13 and t(4;14) status.

Methods: The MM016 trial is a multicenter single-arm open label expanded access program for Lenalidmide in previously treated MM. Pts received Dex 40 mg orally days 1–4, 9–12, 17–20 and Len 25 mg daily orally on days 1–21 of 28Day cycle. Beginning with cycle 5, Dex was reduced to 40 mg days 1–4 only. Fluorescence in situ hybridization (FISH) detected the presence or absence of deletion 13 and t(4;14) on interphase bone marrow aspirates obtained either at the time of initial diagnosis or relapse. Commercially available FISH probes were used to detect of del13q (D13S15 and D13S319) and t(4;14)(p16;q32) (LSI FGFR3 and LSI IGH). EBMT/IBMTR criteria were used to define RR. EFS was defined as the time from initiation of treatment with Len/Dex to the first occurrence of disease relapse, progression, death from any cause as of the date of this analysis (July 4, 2006).

Results: To date 36 patients were enrolled at our site: median age was 61 yrs (41–76), median time from diagnosis was 77.5 months (range: 19.5–3018) median β2 microglobulin 4.1 mg/dl (1.3–17.5), median number of prior treatments of 2 (2–4) with 11 patients (31%) previously treated with Thalidomide, 23 (64%) with Bortezomib and 44.5 % had ASCT. Del 13 and t(4;14) were detected in 16(44.5%) and 7(19.4%) patients respectively. 6/16 (37.5%) with del13 also had t(4;14) as opposed to only 1 patient (5%) in the no del13 group. The del13 vs no del13 groups were balanced with respect to major prognostic factors (age, albumin, DS stage, and lines of prior therapy); β2 microglobulin was higher in the del 13 group (median 5.2 vs 3.3). The overall response RR (CR+PR) to Len/Dex was 83%, 90% for the no del13 group and 75% in the del 13 group. At the time of this analysis 8 events (6 deaths, 2 relapses) have occurred (22%), 5 in the non del13 group. EFS estimates at 6 months were similar in the 2 groups [non del13: 73% vs 81% with del13; p=0.61]. The RR (CR+PR) for t(4;14) and non t(4;14) groups were also identical (71.5% and 86% respectively) with similar 6 mos EFS [71.4% vs. 72.4%; p=0.66]. EFS was also similar when results were analyzed according to age (< or > 65), prior transplant or prior thalidomide.

Conclusion: Treatment with Lenalidomide with Dexamethasone may overcome the poor prognosis conferred by deletion 13 and/or t (4; 14) relative to event free survival and response rate. Updated results from a longer follow-up will be presented at the meeting.