Immunotherapy in hematological malignancies: Current landscape and future directions

Immunotherapy is a therapeutic approach that targets and destroys cancerous cells by enhancing or modifying the host’s own immune system. It has been shown to provide long-lasting remissions and extend options beyond traditional chemotherapy and hematopoietic stem cell transplantation and has revolutionized the therapeutic landscape of hematological malignancies. The immunotherapeutic modalities used to treat different hematologic cancers are discussed in this review. These include monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), chimeric antigen receptor T (CAR-T)-cell therapies, immune checkpoint inhibitors (ICIs), therapeutic cancer vaccines, and oncolytic viruses (OVs). mAbs such as rituximab and daratumumab and ADCs such as polatuzumab and brentuximab vedotin remain a key component of established immunotherapeutic strategies for the treatment of non-Hodgkin lymphoma, Hodgkin lymphoma, and multiple myeloma (MM). BiTEs, especially blinatumomab, have demonstrated remarkable efficacy in treating relapsed or refractory acute lymphoblastic leukemia with positive minimal residual disease. A revolutionary development in immuno-oncology, CAR-T-cell therapy provides deep and long-lasting remissions in MM, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and acute lymphoblastic leukemia. In certain hematologic malignancies such as primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma, ICI, particularly those that target programmed cell death protein 1/programmed death-ligand 1 (PD-1/PDL-1) (nivolumab and pembrolizumab), has shown promise. OVs and therapeutic cancer vaccines are still under development, with the aim to alter the immunosuppressive tumor microenvironment and elicit tumor-specific immune responses. In spite of these developments, difficulties still exist. Broader application is limited by immune-related side effects, treatment resistance, cost, immune escape, and restricted access in low-resource environments. To improve efficacy while lowering toxicity, future directions include developing personalized immunotherapy, improving combination strategies, and improving predictive biomarkers.