Lenalidomide Is Effective Therapy for Relapse After Allogeneic Stem Cell Transplant for Multiple Myeloma.

Abstract 3064

Allogeneic stem cell transplantation (Allo-SCT) can result in long-term remissions in patients with multiple myeloma although it's overall role in disease management remains controversial. Patients who relapse after AlloSCT have limited treatment options. We evaluated the response and tolerance of lenalidomide monotherapy administered to patients with multiple myeloma who progressed or relapsed by EBMT criteria after Allo-SCT. Patients were required to have an ECOG PS of ≤2, ANC ≥1.5 × 10⁹/l, Plts ≥50 × 10⁹/l, creatinine ≤2, bilirubin ≤1.5, SGOT and SGPT ≤2 times ULN. Patients were allowed to take prednisone for acute GVHD but were excluded for GVHD ≥ grade 3. The initial starting dose of lenalidomide was 25 mg orally for 21 of 28 days. Dose reductions after cycle 1 were allowed for neutropenia, thrombocytopenia or other dose related toxicities. Eighteen patients, 5 female, and median age of 48 years (range 28–61) enrolled a median of 12 months (range 3–104) following transplant. Patients were transplanted from 11 matched related donors, 6 matched unrelated donors and 1 mismatched unrelated donor. Conditioning regimens were, fludarabine, 2Gy TBI for 16 and busulfan, melphalan for 1. One patient had 2 allografts from the same donor; the first with cyclophosphamide, fludarabine, the second after intermediate dose melphalan. Treatment duration of lenalidomide was a median of 8 months (range 1–51). Common grade 1–2 adverse events included diarrhea (17%) or constipation (11%), fatigue (17%), myalgias (17%), nausea (11%) and neuropathy (11%). Ten patients required dose reductions to 5–20 mg at a median of 3 cycles (range 1–12); 8 for neutropenia; 1 for thrombocytopenia, and 1 for myalgias and weakness. Serious adverse events N=5, included H1N1 influenza (2), bacterial pneumonia (2), and fever, myalgia and hypoxia. In addition, 2 patients died at 3 and 5 months of GVHD that occurred within 1 month of dosing. One death was gastrointestinal GVHD, the second from liver GVHD in a patient who was enrolled but later deemed ineligible due to elevated SGOT and SGPT by the time of study entry. These were the only 2 patients who discontinued lenalidomide due to GVHD. Three patients were on prednisone 0.5–1 mg/kg for 2, 2, and 11 months for GVHD, but only 1 patient was started on prednisone after initiation of lenalidomide. These results are in contrast to a reported 47% rate of discontinuation of lenalidomide used for maintenance after allografting due to GVHD (Kneppers, et al. Blood 118:2413, 2011) The differences between the two trials may result from the later start of lenalidomide administration in our trial (12 months v. 3 months). Best responses included CR (7), VGPR (1), PR (3), MR (1) and SD (2) for an overall response rate (≥PR) of 61%. Nine patients discontinued therapy due to PD at 1–15 months. Five patients have died from PD. Seven patients remain on therapy at a median of 33 months (range 8–51), 5 in CR. Lenalidomide for relapse of multiple myeloma after allografting can result in extended disease control in 38% of patients.