Targeting the Immune Microenvironment in Chronic Lymphocytic Leukemia: An Evolving Therapeutic Strategy

European Journal Of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ABSTRACT Although small molecule inhibitors that target the aberrant signaling pathways and molecular defects of chronic lymphocytic leukemia (CLL) result in improved survival benefits vs. traditional chemoimmunotherapy or chemotherapy, treatment resistance may later, reflecting intrinsic tumor heterogeneity, persistence leukemic clone, presence microenvironment, which supports disease clone. Patients with CLL have immune‐related abnormalities T lymphocyte subset composition, immune synapse formation, other dysregulations. Cellular interactions between clone its microenvironment provide therapeutic opportunities to these pathogenesis pathways, potentially improving patient's functions clinical outcomes targeted therapies. At present, despite lack response checkpoint CLL, they showed promising efficacy patients Richter transformation. Together CD19‐targeted chimeric antigen receptor–modified cell (CAR‐T) therapy, novel bispecific antibodies immunotherapies are being investigated improve for relapsed refractory (R/R) as exemplified by epcoritamab, a antibody recently demonstrated initial R/R high‐risk subgroups, including those TP53 aberrations unmutated genes encode immunoglobulin variable heavy chain region ( IGHV ). Furthermore, address escape cancer cells issues impact durability single‐targeted cell‐redirected therapies, strategies such trispecific combination therapies increase specificity activation. In summary, there is emerging evidence counteract immunosuppressive responses, decrease risk infection, overcome resistance.

Language: Английский

Immunotherapy in chronic lymphocytic leukemia: advances and challenges

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 10, 2025

Abstract Chronic lymphocytic leukemia (CLL) is characterized as a clonal proliferation of mature B lymphocytes with distinct immunophenotypic traits, predominantly affecting the middle-aged and elderly population. This condition marked by an accumulation within peripheral blood, bone marrow, spleen, lymph nodes. The associated immune dysregulation predisposes CLL patients to higher risk secondary malignancies infections, which significantly contribute morbidity mortality rates. advent immunotherapy has revolutionized prognosis CLL, advancing treatment modalities offering substantial benefits patient outcomes. review endeavors synthesize scrutinize efficacy, merits, limitations current immunotherapeutic strategies for CLL. aim inform selection optimal regimens tailored individual needs. Furthermore, juxtaposes various therapeutic combinations elucidate comparative advantages each approach, ultimate objective enhancing quality life.

Language: Английский

BCL-2 and BTK inhibitors for chronic lymphocytic leukemia: current treatments and overcoming resistance

Expert Review of Hematology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

In the last decade, BTK inhibitors and BCL-2 inhibitor venetoclax have replaced immunochemotherapy in treatment of CLL.

Language: Английский