Multiple Myeloma (MM) is a morbid disease which can only be cured with an allogeneic hematopoietic stem cell transplant (HSCT). Approximately 50% of allotransplanted patients will relapse, with a median survival of 5 years. Better approaches to improve disease control at relapse, while decreasing toxicity, are urgently needed. Relapse after allogeneic transplant is a failure of the graft versus MM effect (GvMM). DLIs can be used to control disease following relapse, but the optimal dose, schedule of administration and drug association remain elusive, while the immunosuppression found in MM patients can compromise their effect. One reason for immunotherapy failure relates to the immunological environment: as much as myeloma cells depend on their microenvironment to survive and proliferate, the immunotherapeutic effect of allogeneic HSCT depends on both systemic and local immunological status to be efficacious. Immunomodulatory drugs such as Lenalidomide (Len) have been tried in various settings after allogeneic transplantation with the aim to reverse immunosuppression and stimulate the GvMM, but if and how Len influences a GvMM and thereby promotes an immunotherapeutic success remained uncharacterized. Therefore, a deeper understanding of the immunological environment in MM patients is needed in order to establish and / or restore a potent GvMM effect. This study proposes the powerful combination of the two following goals, one clinical and one biological : 1. Clinical: The investigators propose a two-step treatment using first Len in association with Dexamethasone (Dex), followed by Donor Leukocytes Infusions (DLIs) to offer an optimal disease control strategy in relapsed patients. The cytoreductive and immunomodulatory effects of Len is expected to induce a permissive immunological environment for the immunotherapeutic activity of DLIs to develop, while the association with Dex will lessen the risk of graft-versus-host disease (GVHD). This treatment combination has the potential to further improve depth of myeloma response, delay myeloma progression and improve patient survival. 2. Biological: In an attempt to gain knowledge on how the GvMM behaves in MM patients post-relapse after having received a combined treatment of Len/Dex/DLIs, the investigators propose to characterize the immune environment of their bone marrow (BM) using both minimal residual disease (MRD) assessement by flow cytometry and an unbiased analysis of the transcriptome at various time points.
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Efficacy of Len-Dex-DLI in patients with relapsed myeloma measured by progression-free survival
Timeframe: 2 years