Phase I/II Multicenter Clinical Trial of Lenalidomide Maintenance After Allogeneic Hematopoietic Cell Transplant (alloHCT) in Patients with High Risk (HR) Multiple Myeloma (MM)

Patients (pts) with HR-MM are in need of new strategies for relapse prevention due to high risk of treatment failure. AlloHCT is an attractive treatment that relies on graft-versus-myeloma to control the disease. Reduced intensity conditioning alloHCT is associated with low transplant-related mortality (TRM), broadening this approach to patients with MM. However, MM progression remains a frequent cause of treatment failure. Maintenance therapy may potentially improve outcomes. The primary objective of this study was to determine the tolerability and safety of lenalidomide maintenance (Len)  for 1 year post-alloHCT in pts with HRMM defined as: relapsed after autologous HCT and/or plasmablastic morphology >2%, β2M ≥ 5.5 mg/L, hypodiploidy, del 13 by standard karyoptyping, t(4;14), t(14;16) or del 17p. Patients who experienced >3 progressions prior to alloHCT, progressed or relapsed after alloHCT, had grade ≥3 graft-versus-host disease (GVHD), on >10 mg/day (d) prednisone, or with fallen donor chimerism prior to Len were excluded. The starting dose of Len was 10 mg/d for 21 of 28d per cycle with monthly dose escalation by 5 mg increments to a maximum of 25 mg/d. Dose reduction to 5 mg/d and 5 mg on alternating days (qod) was allowed to control for toxicity. Thirty patients who received reduced intensity conditioning were enrolled, with a median age of 54 (range 38-68), 57% achieved very good partial response (VGPR) or better prior to Len, 40% had unrelated donors and 97% received peripheral blood grafts. The median time from alloHCT to Len was 96d (range 66-171). Among 29 evaluable patients, a total of 200 cycles were initiated and 177 were completed, with 45% at 10 mg/d, 17% at 5 mg/d and 21% at 5 mg qod. 17% of patients received >10mg/d. 8 patients terminated maintenance during the first cycle, and 10 (34%) completed treatment. Reasons for maintenance discontinuation were acute GVHD (37%), MM progression (33%), neutropenia (10%), skin rash (10%) and infection (10%). Grade 3-4 neutropenia was the most common reason for lowering dose or interrupting cycles. Complete response (CR) was the best response of 55% of pts, and 4 of 14 pts not in CR at the start of maintenance achieved CR after 2-5 cycles. Cumulative incidence of MM progression from start of maintenance was 28% (95% CI, 12-48%), TRM was 3% (0-12%) and grades ≥3 acute GVHD was 17% (6-33%). 12-month probabilities of progression-free (PFS) and overall survival from initiation of Len were 68% (95% CI 46-83%) and 88% (95% CI 67-96%). Despite Len being completed in only 34% of pts, this drug appears to be generally well tolerated although dose reductions were frequently required due to neutropenia. Lowering starting doses and growth factor support should be considered when using Len in this setting. Survival outcomes observed in this study suggest a benefit of maintenance therapy in pts with HRMM after alloHCT.