To improve the outcome of allogeneic stem cell transplantation (allo-SCT) in multiple myeloma as part of first-line treatment, we prospectively investigated the feasibility and efficacy of lenalidomide maintenance. Patients started maintenance 1 to 6 months after nonmyeloablative allo-SCT. Lenalidomide was dosed 10 mg on days 1 to 21 of a 28-day schedule for a total of 24 cycles. Peripheral blood samples were taken to evaluate immune modulating effects. Thirtyfive eligible patients were enrolled, and 30 started with lenalidomide. After 2 cycles, 14 patients (47%) had to stop treatment, mainly because of the development of acute graft versus host disease (GVHD). In total, 13 patients (43%) stopped treatment because of development of GVHD, 5 patients (17%) because of other adverse events, and 5 patients (17%) because of progression. Responses improved in 37% of patients, and the estimated 1-year progression-free survival from start of maintenance was 69% (90% confidence interval, 53%-81%). Lenalidomide increased the frequency of human leukocyte antigen-DR ؉ T cells and regulatory T cells, without correlation with clinical parameters. In conclusion, lenalidomide maintenance 10 mg daily after nonmyeloablative allo-SCT with unmanipulated graft in multiple myeloma patients is not feasible, mainly because of the induction of acute GVHD. This trial
Donor lymphocyte infusions (DLI) can induce durable remissions in multiple myeloma (MM) patients, but this occurs rather infrequently. As the graft-versus-tumor (GvT) effect of DLI depends on the presence of host-dendritic cells (DCs), we tested in a phase I/II trial whether the efficacy of DLI could be improved by simultaneous vaccination with host-DCs. We also analyzed the possibility of further improving the GvT effect by loading the DCs with peptides of mismatched hematopoietic cell-specific minor histocompatibility antigens (mHags). Fifteen MM patients not responding to a first DLI were included. Eleven patients could be treated with a second equivalent dose DLI combined with DC vaccinations, generated from host monocytes (moDC). For four patients, the DC products did not meet the quality criteria. In four of the treated patients the DCs were loaded with host mHag peptides. Toxicity was limited and no acute GvHD occurred. Most patients developed objective anti-host T-cell responses and in one patient a distinct mHag-specific T-cell response accompanied a temporary clinical response. These findings confirm that DLI combined with host-DC vaccination, either unloaded or loaded with mHag peptides, is feasible, safe and capable of inducing host-specific T-cell responses. The limited clinical effects may be improved by developing more immunogenic DC products or by combining this therapy with immune potentiating modalities like checkpoint inhibitors.
2285 Poster Board II-262 The phase II HOVON 76 study examines 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 months following non myeloablative allogeneic stem cell transplantation (NMA allo-SCT). Patients with newly diagnosed Multiple Myeloma who had received intensive treatment including autologous stem cell transplantation (auto-SCT) and have a HLA identical sibling can be included. The NMA allo-SCT is performed within 2-6 months after the auto-SCT after a conditioning regimen of 2Gy total body irradiation. Immunosuppression consists of mycophenolate mofetil 15 mg/kg twice daily until day +84 and ciclosporin 4.5 mg/kg twice daily until day +120. Lenalidomide is started between 1 and 6 months after allo-SCT but preferably within 3 months. Before start the absolute neutrophil count must be ≥ 1.0 × 109/L and platelets ≥ 75 × 109/L. Acute graft versus host disease (GvHD) is an exclusion criterion to start with Lenalidomide except when affecting the skin for less than 50%. If during treatment acute GvHD grade II or higher develops Lenalidomide is stopped and only re-initiated at a lower dose level of 5 mgr once GvHD resolves within 2 months. Dose reduction is also applied in case of other CTCAE grade 3 or higher toxicities, including bone marrow suppression. As of January 2008, 31 patients have been included from 5 academic hospitals. Patients are predominantly male (68%) and median age is 53 years (range 32-65). Partial or complete treatment data are currently available from 24 patients. The total of maximal CTCAE grade 3 and 4 toxicities reported were 50% and 17%, respectively and consists of blood/bone marrow toxicity grade 3 in 29% and grade 4 in 13%, metabolic/laboratory 25% and 4% and dermatology grade 3 in 8%. Seven serious adverse events have been reported, consisting of acute GvHD of the liver in 3 patients, 1 acute GvHD of the intestines, 1 pleural effusion after start of prednisone treatment for skin GvHD, 1 EBV reactivation with fever and malaise, 1 fever of unknown origin. All patients are alive at this moment. After 1 cycle of Lenalidomide 6/24 patients (25%) went off protocol treatment mainly due to the development of acute GvHD (n=4), 1 because of progression and 1 refusal to continue. After cycle 2 another 4 patients (17%) went off protocol treatment due to adverse events and/or dose reductions below 5 mgr. Consequently only 58% of patients could continue with Lenalidomide maintenance after cycle 2. Of those patients, 2 went off protocol due to disease progression, 2 because of GvHD and 2 because of adverse events/dose reductions below 5 mgr after cycles 3-11. In conclusion, the most encountered toxicity with Lenalidomide maintenance treatment after NMA allo-SCT is bone marrow toxicity and acute GvHD. The incidence of GvHD is not higher than expected from our previous NMA allo-SCT study HOVON 54 without Lenalidomide treatment. Because of this toxicity only 58% of patients could continue with treatment after cycle 2. An update of the results with longer follow up will be presented. Disclosures: Off Label Use: lenalidomide is indicated for treatment of relapse multiple myeloma, in this study it is used as maintenance treatment after first line therapy.
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