European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Abstract

Chimeric antigen receptor (CAR) T cells (CAR-T) have dramatically changed the treatment landscape of B-cell malignancies, providing a potential cure for relapsed/refractory patients. Long-term responses in patients with acute lymphoblastic leukemia and non Hodgkin lymphomas have encouraged further development in myeloma. In particular, B-cell maturation antigen (BCMA)-targeted CAR-T have established very promising results in heavily pre-treated patients. Moreover, CAR-T targeting other antigens (i.e., SLAMF7 and CD44v6) are currently under investigation. However, none of these current autologous therapies have been approved, and despite high overall response rates across studies, main issues such as long-term outcome, toxicities, treatment resistance, and management of complications limit as yet their widespread use. Here, we critically review the most important pre-clinical and clinical findings, recent advances in CAR-T against myeloma, as well as discoveries in the biology of a still incurable disease, that, all together, will further improve safety and efficacy in relapsed/refractory patients, urgently in need of novel treatment options.

Allogeneic Stem Cell Transplantation in Multiple Myeloma

“…According to the European Society for Blood and Marrow Transplantation (EBMT) guidelines, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-SCT) is the standard of care for these transplant-eligible patients with newly diagnosed MM [ 8 ]. Over the last decades, new effective therapeutic agents were developed, especially for elderly patients with relevant comorbidities ineligible for auto-SCT and those with relapsed and/or refractory multiple myeloma (RRMM) [ 9 , 10 , 11 ], including immunomodulatory drugs (IMID), proteasome inhibitors (PI), monoclonal antibodies, inhibitors of histone deacetylases, bispecific antibodies, chimeric antigen receptor T (CAR-T) cells and others [ 7 , 12 , 13 , 14 , 15 ]. Due to this remarkable increase of treatment options, and thus an often much deeper remission after optimized first-line therapy and the availability of effective salvage therapies, survival of MM patients has substantially improved over the last years [ 16 , 17 , 18 ].…”

Donor Lymphocyte Infusion to Enhance the Graft-versus-Myeloma Effect

“…To date, no specific information is available on the efficacy and safety of DLI after different transplant settings or maintenance approaches. Moreover, other cellular therapy approaches such as chimeric antigen receptor T-cell therapy, which was most recently approved for relapsed/refractory MM [56], and other immunotherapeutic approaches such as bispecific antibodies, will surely challenge alloSCT and DLI even further [57]. With promising responses across immunotherapeutic approaches, the myeloma community may be confident that immunotherapy will manifest itself for personalized myeloma therapy, although a cure does not seem achievable yet using these new treatment options.…”

CAR-T therapy alters synthesis of platelet-activating factor in multiple myeloma patients

“…3 Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd, Shanghai, China. 4 Department of Hematology, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.…”

“…Strikingly, the CAR-T cell therapy has achieved satisfactory efficacy in patients with relapsed or refractory MM in recent years [ 3 ]. However, cytokine release syndrome (CRS) and clinical efficacy have become the major obstacles which limit the application of CAR-T in clinics [ 4 ]. To explore the potential biomarkers in plasma, we uniquely imported metabolomics analytic techniques and examined the profile changes of metabolites and lipids in plasma from 17 relapsed or refractory MM patients post-CAR-T therapy (Fig.…”