Len/Dex/DLI in Relapsed Multiple Myeloma After Allogeneic Stem Cell Transplant
Status:
Recruiting
Trial end date:
2024-01-29
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2
Details
Lead Sponsor:
Ciusss de L'Est de l'Île de Montréal
Collaborators:
Celgene Centre de Commercialisation en Immunothérapie du Cancer