Immunotherapy in Hematologic Malignancies: Emerging Therapies and Novel Approaches

Abstract

Immunotherapy is extensively investigated for almost all types of hematologic tumors, from preleukemic to relapse/refractory malignancies. Due to the emergence of technologies for target cell characterization, antibody design and manufacturing, as well as genome editing, immunotherapies including gene and cell therapies are becoming increasingly elaborate and diversified. Understanding the tumor immune microenvironment of the target disease is critical, as is reducing toxicity. Although there have been many successes and newly FDA-approved immunotherapies for hematologic malignancies, we have learned that insufficient efficacy due to disease relapse following treatment is one of the key obstacles for developing successful therapeutic regimens. Thus, combination therapies are also being explored. In this review, immunotherapies for each type of hematologic malignancy will be introduced, and novel targets that are under investigation will be described.

Keywords: antibody–drug conjugate; chimeric antigen receptor; hematologic malignancy; immune checkpoint; lymphocyte.

Figure 1

Types of hematologic malignancies and immunotherapies that received FDA approval. Hematologic malignancies are categorized into leukemia, lymphoma, and myeloma. Disease characteristics and subtypes are described and currently available immunotherapies approved by FDA are listed. In the middle circle, targets for immunotherapeutic approaches specific to each disease type are shown. ADC: antibody–drug Conjugate; ALCL: anaplastic large-cell lymphoma; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; ATCLL: acute T cell leukemia/lymphoma; B-ALL: B cell acute lymphoblastic leukemia; BPDCN: blastic plasmacytoid dendritic cell neoplasm; CAR: chimeric antigen receptor; CLL: chronic lymphocytic leukemia; CML: chronic myeloid leukemia; CTCL: cutaneous T cell lymphoma; DLBCL: diffuse large B cell lymphoma; FL: follicular lymphoma; HL: hodgkin lymphoma; ICI: immune checkpoint inhibitor; MCL: mantle cell lymphoma; MM: multiple myeloma; MPN: myeloproliferative neoplasm; NHL: non-Hodgkin lymphoma; PV: polycythemia vera. please refer to the manuscript for other abbreviations. The list of drugs can be searched at https://www.cancer.gov/about-cancer/treatment/drugs/.

Figure 2

Emerging immunotherapies with new targets for hematologic malignancies. Targets for immunotherapies that are effective in preclinical or clinical trials are depicted. Blue receptors/antigens are immune checkpoints. Molecules in red represent targets for monoclonal antibody (mAb), bispecific T cell engager (BiTE), or chimeric antigen receptor (CAR)-T/NK therapies, while dark yellow means immunotherapy targets that have not been investigated for the CAR-T cell approach.