A Randomized Clinical Trial of Lenalidomide and Dexamethasone with and without Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Interim Study Results,

High dose chemotherapy combined with autologous stem cell transplantation (ASCT) as opposed to conventional chemotherapy improved progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) and is currently the standard of care for newly diagnosed MM patients less than 65 years old. Over the last decade, novel agents such as lenalidomide or bortezomib have dramatically improved MM outcomes with similar response rates as ASCT and the role of upfront ASCT has become more controversial. Therefore the goal of this randomized clinical trial is to determine the role of upfront ASCT in newly diagnosed myeloma patients receiving novel agent lenalidomide and low-dose dexamethasone induction.

Patients aged ≥18 years with newly confirmed, measurable MM in stage 2 and 3 (Salmon Durie) and meeting CRAB criteria were enrolled. Patients were randomized to transplant (Arm A) or to non-transplant (Arm B). Patients in Arm A received 4 cycles of lenalidomide (25mg days 1 – 21) plus low-dose dexamethasone (40mg days 1,8,15,22) followed by ASCT conditioned with 200 mg/m² melphalan (LD+ASCT); Arm B patients received 8 cycles of lenalidomide plus low-dose dexamethasone (LD alone). Both arms received stem cell collection after 4 cycles of therapy if patients achieved at least a partial remission (PR). Patients with stable disease (SD) or progressive disease (PD) went off study. The primary objective was to compare best response. The secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS) and evaluation of secondary malignancies in both arms.

From February 2008 to May 2011, 44 patients with newly diagnosed MM were randomized. The patient characteristics were as follow: median age of the patients was 61.7 years (range 48∼75), 45.5% female and 55.5% male patients, ISS stage I 31%, II 51% and III 18%. 40 patients were eligible for evaluation and 20 patients were randomized to Arm A or Arm B, respectively. The data were analyzed according to latest IMWG response criteria (Blood. 2011 May 5;117(18):4691–5). In an intention to treat analysis, patients in Arm A (LD + ASCT), achieved a 100% Overall Response Rate (ORR) with 40% PR (n=8) and 60% Very Good Partial Response (VGPR) (n=12). In Arm B (LD only) the ORR was 75% (n=15), including 15% CR (n=3), 35% VGPR (n=7), 25% PR (n=5), 20% SD (n=4) and 5% PD (n=1). The ORR was significantly superior in the LD+ASCT group compared to LD alone (p=0.047). After a median follow-up of 25.3 months, 17 patients have PD (8 in LD+ASCT and 9 in LD alone), 6 have died (1 in LD+ASCT and 5 in LD alone). DOR, PFS and OS were not significantly different in both groups. OS showed a trend to be superior in patients treated with LD+ASCT (p=0.08). (Table 1). One patient in the LD+ASCT arm developed MDS 13 months after start of therapy.

Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed MM patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR. There was no difference in terms of DOR or PFS with a trend of superior OS in the LD+ASCT group. The study requires careful interpretation based on the low patient number and relatively short follow up, but supports the continued role of upfront consolidative ASCT in newly diagnosed MM patients. The incidence of secondary malignancy was low with the development of 1 MDS. Updated data on response and overall survival will be available at the time of presentation.

Roodman:Amgen: Consultancy; Millennium Pharmaceuticals: Consultancy. Raptis:Millennium: Speakers Bureau; Celgene Corp: Speakers Bureau; Eisai: Speakers Bureau. Lentzsch:Celgene Corp: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; prIME Oncology: Honoraria; Imedex: Honoraria; Clinical Care Options: Honoraria.