CURRENT APPROACHES IN CANCER IMMUNOTHERAPY

tibbibiyolojiozel-3-2-25kapak

Resistance Mechanisms in Multiple Myeloma Immunotherapy

Ece VURALa , Meral BEKSAÇb
aSivas State Hospital, Clinic of Hematology, Sivas, Türkiye
bİstinye University Liv Hospital Ankara, Department of Hematology, Ankara, Türkiye

Vural E, Beksaç M. Resistance mechanisms in multiple myeloma immunotherapy. Sunguroğlu A, ed. Current Approaches in Cancer Immunotherapy. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.59-64.

ABSTRACT
Triple-class and penta-refractory multiple myeloma (MM) have extremely poor outcomes requiring innovative therapeutic strategies such as bispecific T-cell engagers, chimeric antigen receptor T cells, and antibody-drug conjugate therapies which have entered the armamentarium of relapsed/refractory myeloma. Similar to most cancer treatment approaches, resistance is an evolving concept after immunotherapy. To achieve a better response, one must know how to deal with most of the elucidated resistance mechanisms in MM immunotherapy. T-cell dysfunction occurs due to T-cell exhaustion and an increase in regulatory T cells. Several tumor characteristics, such as tumor burden, the antigenic escape mechanism of B-cell maturation antigen (BCMA), and G-protein-coupled receptor class C group 5 member D (GPRC5D) antigens can be listed among the multiple causes. Additionally, the tumor microenvironment may exhibit features such as an increase in soluble BCMA and immunosuppressive cells. All these situations listed above need to be considered among resistance mechanisms and specifically addressed to develop solution strategies when response is not achievable.

Keywords: Immunotherapy; multiple myeloma; T-lymphocytes

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