Enhancing immunotherapy efficacy in multiple myeloma and chronic lymphocytic leukemia: from combinatorial therapeutic approaches to gut microbiota modulation.

Multiple myeloma and chronic lymphocytic leukemia are among the most common hematological tumors. Although first-line therapies are initially effective, their clinical benefit is frequently compromised by the emergence of acquired drug resistance. In recent years, novel immunotherapies such as checkpoint inhibitors, chimeric antigen receptor T-cells, and bispecific antibodies are showing promising results in preclinical studies, achieving high rates of response and remission in some cases. However, despite these advances, durable responses are not achieved in all patients, and treatment failure, toxicity and resistance remain major clinical challenges. In this review, we have comprehensively examined current strategies aimed at optimizing immunotherapy efficacy through rational combination approaches including novel immunotherapies with established standard-of-care agents as well as emerging treatments. Moreover, we have explored the growing evidence supporting the role of the gut microbiota in both B-cell malignancies, focusing on its influence on disease biology and modulation of immunotherapeutic responses to further improve patient outcomes. Finally, we have addressed the current challenges and future perspectives in the field of immunotherapy in both diseases.