The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma

Abstract

Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients [1]. Over the past decade, we have witnessed the “era of monoclonal antibody (moAb)”, setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal outcome. Emerging T-cell directing therapies, such as bispecific antibody (bsAb) and chimeric antigen receptor T cells (CAR T) have shown unprecedented responses and outcomes in these heavily pretreated and treatment-refractory patients. Their clinical efficacy combined with high tolerability will likely lead to the use of these agents earlier in the treatment course and there is great enthusiasm that a combination of T cell directed therapy with moAbs can lead to long duration remission in the near future, possibly even without the need of high dose chemotherapy and stem cell transplantation. Herein, we summarize the role of naked moAbs in MM in the context of newer immunotherapeutic agents like bsAb and CAR T therapy.

Updates in the Management of Multiple Myeloma from the American Society of Hematology Meeting 2021

“…The phase III German-speaking Myeloma Multicenter Group (GMMG HD6) trial studied the addition of the anti-SLAMF7 monoclonal antibody (mAb) elotuzumab to lenalidomide, bortezomib and dexamethasone (RVd) in induction, consolidation and maintenance treatment in transplanteligible NDMM. 12 Along the lines of the ELOQUENT-1 13,14 and SWOG 1211 15 studies, the addition of elotuzumab did not result in improved PFS or OS in NDMM. Is this the end of the road for elotuzumab therapy in NDMM?…”

Clinical efficacy of sequencing CD38 targeting monoclonal antibodies in relapsed refractory multiple myeloma: A multi‐institutional experience

“…Multiple Myeloma (MM) remains largely incurable with a small proportion of patients attaining long‐term disease control. Monoclonal antibodies (MoAbs) targeting plasma cell surface antigens play an increasing role in improving outcomes 1 . Among these, the CD38‐targeted MoAbs daratumumab (Dara) and isatuximab (Isa) are widely used for relapsed MM Isa differs from Dara in its mechanism of action with more antibody‐dependent rather than complement‐mediated cytotoxicity and relatively less reliance on Fc receptor‐mediated crosslinking for induction of apoptosis.…”

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: first reported case

“…Emerging T-cell directing therapies, such as bispecific antibodies (bsAbs) and chimeric antigen receptor T cells (CAR-T), have demonstrated remarkable responses and outcomes in extensively treated and treatment-resistant patients (1). Despite significant advances in the treatment of MM, central nervous system (CNS) involvement remains a challenging and rare complication that can lead to severe neurological symptoms and impact patient outcomes.…”