Novel Experimental Drugs for Treatment of Multiple Myeloma

Abstract

Multiple myeloma (MM) is the second most frequent hematological malignancy characterized by bone marrow aberrant plasma cells proliferation leading to a genetic complex and heterogeneous disease, with a median survival ranging from two to more than 10 years. By using new drugs such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs) in different combinations and high-dose therapy followed by auto-transplantation, there has been an amazing improvement in the outcome of this disease in recent years. Despite this, MM is still considered an incurable disease, characterized by remission periods alternated with relapse/progression episodes finally leading to resistant disease. In particular, patients who become refractory to PIs, IMiDs and mAbs have a very poor outcome. Moreover, to overcome resistant residual disease, a large combination of drugs will be increasingly used in early lines of therapy; this further reduces the therapeutic options at each relapse. This natural history means that MM always needs new drugs/strategies to overcome the incoming resistance. New combinations of naked mAbs are becoming the therapy of choice for patients refractory to lenalidomide and/or PI; conjugated mAbs will be useful in triple- and more-refractory patients; CAR-T cells and bispecific mAbs have shown relevant results in very advanced stages of disease. In this review, we reported the results of these new therapies and explored their potential applications. Personalized and precision medicine seem to be the new frontier of cancer treatment. Although no single or few factors have been identified as disease drivers in MM, recurrent gene mutations were recognized and specific compounds targeting these alterations were developed and studied. Therefore, we reviewed these targeted drugs to try to understand what the best therapeutic strategy in MM is.

miR-22 Modulates Lenalidomide Activity by Counteracting MYC Addiction in Multiple Myeloma

“…Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of malignant plasma cells in the bone marrow (BM), associated with bone disease, serum monoclonal gammopathy, immune suppression, and end-organ damage [1]. Despite the recent relevant advancement in the treatment of MM by new drugs, which have significantly improved patients' outcome, MM is still an incurable malignancy [2]. Therefore, a deeper molecular understanding of its pathogenesis and the investigation of crucial nodes of MM vulnerability are needed to develop novel therapeutic strategies against still undruggable critical targets, such as MYC [3].…”

Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real-world chart review study

“…While the safety and efficacy of daratumumab in front line and later lines has been well documented in clinical trials, real-world insights on treatment patterns and outcomes among patients with MM initiated on daratumumab, including among patients treated and re-treated with daratumumab, [ 12 ] are limited. In light of the rapidly-evolving treatment landscape in MM, [ 13 ] there is a need to understand real-world outcomes associated with daratumumab among patients with newly-diagnosed and relapsed or refractory MM. Therefore, the goal of this study was to describe the real-world treatment patterns and clinical outcomes of adult patients with MM receiving daratumumab across different lines of therapy.…”

Aggressive Plasmablastic Myeloma With Extramedullary Cord Compression and Hyperammonemic Encephalopathy: Case Report and Literature Review

“…Nevertheless, patients with +1q and other co-occurring +1q or high-risk cytogenetic abnormalities should be considered at very high risk for early disease progression. Targeting of specific gene mutations with specific compounds appears to be a promising avenue for targeted myeloma therapies, especially in patients refractory to combinations of the above novel agents (24). Multiple clinical trials are ongoing and examining other potential molecular targets including the bispecific T-cell engager (BiTE) molecule and chimeric antigen receptor T-cell therapies directed against CD19, already approved in the treatment of other hematological malignancies (25)(26)(27).…”