Response Adapted Therapy Using Single Agent Lenalidomide in Older Adults with Newly Diagnosed Standard Risk Multiple Myeloma

Rajkumar et al. reported improved survival with lenalidomide and low dose dexamethasome as compared with lenalidomide and high dose dexamethasone (Rajkumar V, Lancet Oncol 2010). In addition, we reported promising outcomes of a retrospective cohort of newly diagnosed multiple myeloma patients treated with single agent lenalidomide(Baz R Leuk Lymphoma. 2010). Accordingly, we conducted this prospective single center open label study to evaluate the efficacy of a response adapted approach using single agent lenalidomide in older adults with newly diagnosed standard risk multiple myeloma.

Eligible patients had symptomatic multiple myeloma without high risk features (b2microglobulin (b2m) ≤5.5, absence of t(4;14), t(14;16), 17p deletion, aneuploidy or 13q by metaphase cytogenetics) and were not eligible or not willing to receive high-dose therapy and stem cell transplant. Patients received lenalidomide 25 mg PO D1–21 every 28 days for 2 cycles. If patients had a minimal response or better (MR, 25% reduction in serum M spike) after 2 cycles, they continued on single agent lenalidomide until progressive disease. If patients had stable disease after 2 cycles, prednisone 100 mg PO D1–5 was added to their lenalidomide. In the event of progressive disease on single agent lenalidomide or on lenalidomide/prednisone, therapy was changed to lenalidomide (at the tolerated dose) and dexamethasone 40 mg PO weekly. Thromboprophylaxis was with aspirin, warfarin or low molecular weight heparin. Responses were per IMWG response criteria. The study was approved by the institutional review board.

Between February 2010 and May 2012, 22 patients were screened and 19 were eligible. The median age was 75 years (range 65–83) and 12 were males. Per protocol, no patient had ISS stage 3 disease but 8 patients had ISS stage 2 and 11 stage 1 (median b2m was 3.2 mg/L (range 2.2–5.5)). 5 patients had 13q deletion by FISH alone, 4 had t(11;14), another 3 had trisomy 11, and 2 had trisomy or tetrasomy 1q. The median baseline creatinine clearance was 66.5 ml/min (range 43–109). After 2 cycles of single agent lenalidomide, 9 patients (47%) had a PR (partial response), 6 (32%) MR, 3 (16%) stable disease (SD), and 1 (5%) progressive disease. The best response to single agent lenalidomide was as follows: 3 had a stringent complete response sCR (16%), 1 (5%) a very good partial remission (VGPR), 8 PR (42%), 4 MR (21%), 2 SD (11%) and 1 PD (5%). The estimated 1 year PFS to single agent lenalidomide is 80%. Five patients required the addition of dexamethasone with the following responses: 1 VGPR, 1 PR, 1 MR, 1 SD and 1 PD; Three patients required the addition of prednisone and the response to lenalidomide prednisone was 1PR, 1 MR, 1 SD. Five patients went off study, 2 for PD and 3 withdrew consent (2 were in PR at the time and 1 in SD). The estimated 1 year PFS for the protocol therapy is estimated at 94%. Eleven patients had dose reduction in lenalidomide; 5 patients to 15mg and 6 patients to 10 mg. Grade 3/4 neutropenia, thrombocytopenia, anemia, febrile neutropenia and fatigue occurred in 58%, 5%, 10%, 5% and 5% of patients respectively.

In this patient population, single agent lenalidomide results in an ORR (PR and better) of 63% and clinical benefit rate (MR and better) of 84% with only a quarter of patients requiring the addition of dexamethasone. A response adapted therapy using single agent lenalidomide is safe and effective in older adults with standard risk myeloma sparing dexamethasone toxicities from the majority of patients. Updated results for ongoing accrual of up to 30 evaluable patients will be presented at the meeting.

Baz:Celgene, Millennium, Bristol Myers Squibb, Novartis: Research Funding. Off Label Use: lenalidomide for newly diagnosed multiple myeloma. Alsina:Millenium: Consultancy, Research Funding. Finley-Oliver:celgene: Speakers Bureau.