Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse

Abstract

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patient-related factors to consider. In this broad scoping review of available therapies in relapsed/refractory multiple myeloma (RRMM), we cover the pharmacologic mechanisms underlying active therapies such as immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), monoclonal antibodies (mAbs), traditional chemotherapy, and Venetoclax. We then review the clinical data supporting the use of these therapies, organized based on drug resistance/refractoriness, and the role of autologous stem cell transplant (ASCT). Approaches to special situations during relapse such as renal impairment and extramedullary disease are also covered. Lastly, we look towards the future by briefly reviewing the clinical data supporting the use of chimeric antigen receptor (CAR-T) therapy, bispecific T cell engagers (BITE), and Cereblon E3 Ligase Modulators (CELMoDs).

A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models

“…These results suggest that both ND and RR patients with high-GPRC5D-expression can expect strong therapeutic effect equivalent to CR with higher probability. Interestingly, our retrospective analysis revealed that a high-risk chromosome abnormality, t (4,14), provokes an increase of GPRC5D expression, which is consistent with a previous study on 48 MM patients in Vienna 5 . This indicates that GPRC5D targeted T cell-redirecting bispecific antibodies are applicable or even preferable for use in patients with high-risk chromosome abnormalities with high unmet medical needs.…”

Progress and prospect of ASCT combined with CAR-T therapy in the treatment of multiple myeloma

“… 57 In the current era of MM treatment, there are excellent treatment plans that can enable approximately 55% of patients to achieve at least 5 years of survival. 58 CAR-T cell therapy can cure some patients with high-grade lymphoma and invasive leukemia. But currently, in the field of MM, there is too little research data on this combination therapy, which is more based on hypotheses and small-scale single-center studies, and lacks a control group.…”

Panorama actualizado en mieloma m�ltiple

“…Se define como recaída a la recurrencia de enfermedad después de lograr un intervalo mayor a 60 días con respuesta al tratamiento previo. Se define como enfermedad refractaria a la ausencia de respuesta a tratamiento previo o a la progresión en los primeros 60 días posteriores a la última línea de tratamiento 27 . La progresión se debe tratar inmediatamente cuando sea identificada, en la tabla 7 se enumeran los criterios que obligan a tratar a un paciente.…”