Lenalidomide Maintenance Following Non Myeloablative Allogeneic Stem Cell Transplantation In Patients with Multiple Myeloma: Results of the HOVON 76 Study

Abstract 3502

The phase II HOVON 76 study examined the efficacy and safety of maintenance treatment with lenalidomide 10 mgr daily for 21 days in a 28 day cycle for a maximum of 24 cycles following non T-cell depleted non myeloablative allogeneic stem cell transplantation (NMA allo-SCT). Patients with newly diagnosed Multiple Myeloma who had received autologous stem cell transplantation (auto-SCT) and had a HLA identical sibling could be included. The NMA allo-SCT was performed within 2–6 months after the auto-SCT after conditioning with TBI 2Gy only. Immunosuppression consisted of mycophenolate mofetil and ciclosporin.

From January 2008 until March 2010, 35 patients from 5 academic hospitals were included. In that same time period 13 patients with NMA allo-SCT first line could not be included due to acute graft versus host disease (GvHD) ≥ grade 2 (8 pts), refusal (3 pts) or failing other inclusion criteria (2 pts). Of those 35 included patients 5 never started with lenalidomide because the study was put on hold and later stopped prematurely. Median age of the remaining 30 patients was 53 years (range 37–65). Patients started with lenalidomide median 12 weeks (range 4–27) after NMA allo-SCT.

During lenalidomide treatment 19 patients (63%) developed acute (late onset) GvHD. GvHD started median 18 days (range 4–247) after start of lenalidomide, 12 of these 19 patients developed GvHD during cycle 1. In 11 patients GvHD resolved completely. Blood samples were taken for cellular analysis and will be reported.

The total of maximal CTCAE grade 3 and 4 toxicities reported were 53% and 23%, respectively and consisted of blood/bone marrow toxicity grade 3 in 27% and grade 4 in 17%, metabolic/laboratory 23% and 7% and dermatology grade 3 in 10%.

Lenalidomide stopping criteria were development of GvHD ≥ 2 and other toxicities CTCAE grade ≥ 3. Eight patients (27%) went off protocol treatment after 1 cycle, mainly due to the development of GvHD. After cycle 2 another 4 patients (13%) stopped treatment and after 4 cycles just 12 pts (40%) could continue. Only 3 patients have completed 24 cycles and 1 pt is still on protocol treatment.

In 10 patients responses improved after start of lenalidomide; from PR to VGPR in 3, from PR to CR in 2 and from VGPR to CR in 5. Nine patients have progressed. Two patients have died; one patient with graft failure due to neutropenic fever and another due to progression. Median follow up is 69 weeks (2-122) and estimated 2 years OS is 93% and PFS 60%.

In conclusion, early lenalidomide treatment following NMA allo-SCT is not feasible mainly due to the development of acute (late onset) GvHD. The occurrence of GvHD was closely related with the start of lenalidomide treatment. In this preliminary analysis no improvement of PFS was demonstrated compared to the HOVON 54 study in which no maintenance treatment after NMA allo-SCT was given.