Multiple Myeloma: An Overview of the Current and Novel Therapeutic Approaches in 2020

Abstract

The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well acknowledged to prolong survival. Lenalidomide monotherapy is the only drug approved in that setting, but many innovations are expected. Older patients, now logically named not transplant-eligible, also took advantage of these breakthrough innovations as most of the recent drugs have a more acceptable safety profile than previous cytotoxic agents. For this heterogenous subgroup, geriatric assessment has become an essential tool to identify frail patients and provide tailored strategies. At relapse, options are now numerous, especially for patients who were not treated with lenalidomide, or not refractory at least. Concerning lenalidomide refractory patients, approved combinations are lacking, but many trials are ongoing to fill that space. Moreover, innovative therapeutics are increasingly being developed with modern immunotherapy, such as chimeric antigen receptor T-cells (CAR-T cells), bispecific antibodies, or antibody–drug conjugates. For now, these treatments are usually reserved to heavily pre-treated patients with a poor outcome. MM drug classes have tremendously extended from historical alkylating agents to current dominant associations with proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38/anti SLAMF7 antibodies. Plus, in only a couple of years, several new classes will enter the MM armamentarium, such as cereblon E3 ligase modulators (CELMoDs), selective inhibitors of nuclear export, and peptide–drug conjugates. Among the questions that will need to be answered in the years to come is the position of these new treatments in the therapeutic strategy, as well as the role of minimal residual disease-driven strategies which will be a key issue to elucidate. Through this review, we chose to enumerate and comment on the most recent advances in MM therapeutics which have undergone major transformations over the past decade.

Identification of three immune molecular subtypes associated with immune profiles, immune checkpoints, and clinical outcome in multiple myeloma

“…MM armamentarium is widely used and almost every patient can acquire adequate strategies and optimal sequences of drugs. [3][4][5][6] Given our increasing understanding of the diagnosis and treatment of MM, now would seem an appropriate time to provide a more robust classification system for MM, which will pave the way for personalized medicine and improve the quality of life and survival of patients with MM. 7 Immunotherapy is considered the fifth pillar of cancer care and represents a paradigm shift in oncology treatment.…”

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors

“…Monotherapies or doublets may also be considered for frail patients, whilst fit or intermediate-fit patients may receive triplets or quadruplets (Figures 3 and 4) [19,30,65,66].…”

Recent Advances on the Pathobiology and Treatment of Multiple Myeloma

“…However, the approval of several new drugs, along with the limited availability of clinical trials comparing various head-to-head possible combinations, make the therapeutic choice at each stage of the disease really complex, as underlined by Bobin et al in their review [12]. Legarda et al instead provide an additional thorough description of the novelties regarding therapeutic modalities against MM, remarking interesting results in TE-patients obtained with the new quadruplet therapies including monoclonal antibodies, D-VTd and D-VRd [13].…”