Utility of measurable residual disease for predicting treatment outcomes with BCR- and BCL2-Targeted therapies in patients with CLL

Wierda, WG; Kipps, TJ; Al-Sawaf, O; Chyla, B; Biondo, JML; Mun, Y; Jiang, Y; Seymour, JF

Author(s): Wierda, WG; Kipps, TJ; Al-Sawaf, O; Chyla, B; Biondo, JML; Mun, Y; Jiang, Y; Seymour, JF;
Details: Publication Year 2022-12,Volume 63,Issue #12,Page 2765-2784
Journal Title: Leukemia & Lymphoma
Publication Type: Review
Abstract: Inhibitors targeting B-cell receptor (BCR) signaling pathway proteins and B-cell lymphoma-2 (BCL2) in chronic lymphocytic leukemia (CLL) are recommended in the first-line and relapsed/refractory disease settings. Measurable residual disease (MRD) is an important prognostic tool in patients treated with the BCL2-targeted agent, venetoclax. We explored the relationship between MRD status and progression-free (PFS)/overall survival (OS) in patients with CLL, following treatment with novel BCR- and BCL2-targeted agents. Compared with chemoimmunotherapy, higher rates of undetectable (u)MRD were achieved with BCL2-targeted therapies; achieving uMRD status was associated with longer PFS and OS than MRD-positivity. Continuous treatment with BCR-targeted agents did not achieve uMRD status in many patients, and outcomes were not correlated with uMRD status. Future clinical trials of targeted treatment combinations could be designed to demonstrate uMRD as a treatment objective, and allow a response-driven, personalized strategy to optimize treatment and improve OS outcomes.
Keywords: Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/drug therapy; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use; Neoplasm, Residual/drug therapy; *Antineoplastic Agents/therapeutic use; Treatment Outcome; Proto-Oncogene Proteins c-bcl-2/genetics; Lymphoid leukemia; pharmacotherapeutics; prognostication
Department(s): Haematology
PubMed ID: 35983732
Publisher's Version: https://doi.org/10.1080/10428194.2022.2098291
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-09 07:31:44

Last Modified: 2025-05-09 07:33:16