Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

Abstract

Multiple myeloma (MM) is still considered an incurable hematologic cancer and, in the last decades, the treatment goal has been to obtain a long-lasting disease control. However, the recent availability of new effective drugs has led to unprecedented high-quality responses and prolonged progression-free survival and overall survival. The improvement of response rates has prompted the development of new, very sensitive methods to measure residual disease, even when monoclonal components become undetectable in patients' serum and urine. Several scientific efforts have been made to develop reliable and validated techniques to measure minimal residual disease (MRD), both within and outside the bone marrow. With the newest multidrug combinations, a good proportion of MM patients can achieve MRD negativity. Long-lasting MRD negativity may prove to be a marker of "operational cure", although the follow-up of the currently ongoing studies is still too short to draw conclusions. In this article, we focus on results obtained with new-generation multidrug combinations in the treatment of high-risk smoldering MM and newly diagnosed MM, including the potential role of MRD and MRD-driven treatment strategies in clinical trials, in order to optimize and individualize treatment.

Autologous Transplantation Using Donor Leukocytes Loaded Ex Vivo with Oncolytic Myxoma Virus Can Eliminate Residual Multiple Myeloma

“…A major challenge with MM is the prevalence of therapy-refractory myeloma within tissue niches that constitute MRD. 11 , 12 , 38 Therefore, alternative therapeutic strategies that assure the complete elimination of MM MRD are required. The use of OVs alone or in combination with other standard therapies is becoming an attractive strategy to target and eliminate relapsed/refractory or residual solid tumors and hematological malignancies.…”

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

“…Although the introduction of new pharmacologic classes, such as proteasome inhibitors (PIs) or immunomodulatory drugs (IMiDs), has revolutionized treatment in the last decades [2], MM remains an incurable disease and almost all patients relapse after a variable period and become refractory to previously used drugs (relapsed/refractory multiple myeloma, RRMM). In clinical practice, the development and introduction of new drugs with unique mechanisms of action and the combination of different drug classes have increased treatment options for RRMM patients and have improved the depth of response in newly diagnosed (ND) MM patients [3].…”

Dual Targeting to Overcome Current Challenges in Multiple Myeloma CAR T-Cell Treatment

“…As the second most common hematological malignancy, MM accounts for 2% of all cancer deaths in the U.S., as of 2019 (1). While the therapy of MM was for decades based on a number of alkylating agents, with melphalan being the prime choice, since the beginning of the century, treatment options for MM patients have been significantly improved by successful applications of immunomodulatory drugs, proteasome inhibitors, histone deacetylases, and by monoclonal antibodies (2). Although each of these novel therapies significantly improved the outcome of patients, MM still remains an incurable disease for the majority of patients.…”