Expression-linked and R-ISS-adapted Stratification for First Line Therapy in Multiple Myeloma Patients
Status:
Not yet recruiting
Trial end date:
2028-10-01
Target enrollment:
Participant gender:
Summary
Multiple myeloma (MM) is a malignant disease of the BM characterized by clonal expansion of
plasma cells. Current guidelines recommend that newly diagnosed transplant-eligible patients
with multiple myeloma (NDMMTE) shall undergo several cycles of induction, followed by one or
two cycles high-dose melphalan followed by autologous stem cell transfusion (ASCT).
Currently, induction therapy schemes usually consist of an immunomodulator (thalidomide or
lenalidomide), a transmembrane glycoprotein CD38 targeting antibody, a proteasome inhibitor,
and dexamethasone. The induction therapy is then followed by stem cell mobilization and
subsequently one or two cycles of high-dose melphalan-chemotherapy based on the initial
cytogenetic findings of the malignant plasma cells and the initial stage of the disease.
Essentially, all NDMMTE patients undergo at least one cycle of high-dose chemotherapy, which
is associated with high morbidity including acute toxicities like cytopenia, infection, and
long-term effects such as myelodysplastic disease (MDS) and secondary malignancies and rarely
death.
Based on preliminary data and published reports, exposure to high-doses of the genotoxic
agent melphalan might render the residual malignant myeloma cells into more aggressive
clones, accelerating relapse by potentially altering stroma. Finally, exposure to melphalan
is well known to increase the possibility of secondary malignant disease development. In MM
patients, high-dose melphalan therapy improves OS and PFS if patients from all risk groups
are taken in consideration. Yet, it remains to be answered, whether also low risk patients
have an additional benefit from high-dose melphalan therapy or whether for these patients, a
less toxic regime would be similarly sufficient with regard to PFS and OS. The challenging
question will be whether the effect of melphalan on initial disease control might be outpaced
by the negative effects as described above. Hence, the sponsor will explore whether treatment
with high-dose melphalan might represent an overtreatment for certain subpopulation myeloma
patients. These patients might be adequately treated without need of high-dose melphalan as
part of the first line treatment. The sponsor, therefore, proposes to use a personalized
approach to evaluate whether patients with a low-risk profile and with a gene expression
profile indicating a standard risk of relapse might be sufficiently treated with an
intensified induction course without subsequent upfront high-dose melphalan chemotherapy.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
University Hopsital Schleswig Holstein Campus Lübeck