Functional Cure as a New Concept of Therapy for Multiple Myeloma

Abstract

Multiple myeloma (MM) is a genetically complex and clinically heterogeneous disease which has been traditionally considered incurable. In the light of new drugs and rising diagnostic potential, more and more attention is being given to a new concept of MM therapy known as “functional cure”. One of its definitions is “the sustaining absence of measurable disease for 5 years or more upon chemotherapy withdrawal with a satisfactory quality of life being maintained”. The present review focuses on the key aspects of MM diagnosis and treatment with the use of the IMWG SLiM-CRAB criteria for identifying asymptomatic patients with high risk for progression within the next 2 years. Special attention is paid to current data for verification of smoldering multiple myeloma (SMM) with high risk for early transformation to symptomatic MM. This review discusses two treatment strategies for high-risk SMM patients including low-intensity therapy options aimed at prolonging the time to progression and intensified therapy aimed at eradicating minimal residual disease (MRD) and achieving possible cure. For newly diagnosed MM patients who are eligible for autologous hematopoietic stem cell transplantation (auto-HSCT), the priority options are induction protocols with 4 active drugs (D-VRd and Isa-VRd) with subsequent auto-HSCT and maintenance therapy. This approach yields durable MRD-negative response in many patients — evidence suggesting that they can achieve functional cure in the long term. In auto-HSCT-ineligible patients, the preferred option is combined therapy with anti-CD38 monoclonal antibodies (daratumumab and isatuximab) showing good results in achieving MRD-negativity and better survival rates. Prospects for MM treatment are bound up with the development of immunotherapy (CAR-T cells and bispecific antibodies) which has proven to be highly effective in refractory MM patients. New treatment methods for newly diagnosed MM open up expanded possibilities of achieving functional cure in a considerable part of patients. Functional cure is becoming a realistic goal of MM therapy, which clearly indicates the need for further studies and development of personalized treatment approaches.