Ibrutinib with Venetoclax in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: A Phase II Study

Swaminathan, M; Ferrajoli, A; Thompson, PA; Burger, J; Borthakur, G; Takahashi, K; Estrov, Z; Bharathi, V; Bataller, A; Kadia, TM; Pemmaraju, N; Daver, N; Jabbour, E; Bose, P; Kanagal-Shamanna, R; Patel, KP; Wang, SA; Garg, N; Hwang, H; Wang, X; Qiao, W; Xu, X; Cruz, N; Ayala, A; Pierce, S; Plunkett, W; Sampath, D; Kantarjian, HM; Keating, MJ; Gandhi, V; Wierda, WG; Jain, N

Author(s): Swaminathan, M; Ferrajoli, A; Thompson, PA; Burger, J; Borthakur, G; Takahashi, K; Estrov, Z; Bharathi, V; Bataller, A; Kadia, TM; Pemmaraju, N; Daver, N; Jabbour, E; Bose, P; Kanagal-Shamanna, R; Patel, KP; Wang, SA; Garg, N; Hwang, H; Wang, X; Qiao, W; Xu, X; Cruz, N; Ayala, A; Pierce, S; Plunkett, W; Sampath, D; Kantarjian, HM; Keating, MJ; Gandhi, V; Wierda, WG; Jain, N;
Details: Publication Year 2026-05-05,Volume 7,Issue #3,Page 431-440
Journal Title: Blood Cancer Discovery
Publication Type: Research article
Abstract: We explored the efficacy of the combination of ibrutinib + venetoclax in patients with relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). This phase II study enrolled 80 patients between July 2016 and September 2018. Patients received ibrutinib for the first 3 cycles, followed by ibrutinib + venetoclax for 24 cycles. Of the 79 treated patients, the median age was 61 years (IQR, 56-69); 65 (65/76, 86%) had unmutated IGHV and 29 (37%) had either del(17p) or a TP53 mutation. The median number of prior treatments was 1 (range, 1-3). The primary endpoint, best complete remission (CR) and CR with incomplete count recovery (CRi), was 67%, with a bone marrow undetectable measurable residual disease [10-4 sensitivity (U-MRD4)] rate of 61%. At 95.5 months of median follow-up, the estimated 7-year progression-free survival rate was 63.3%. Grade ≥3 neutropenia and thrombocytopenia occurred in 38% and 13% of patients, respectively. The 24-cycle ibrutinib + venetoclax combination led to high rates of CR/CRi and bone marrow U-MRD4 in patients with R/R CLL. SIGNIFICANCE: The 24-cycle ibrutinib + venetoclax combination led to high rates of CR/CRi and bone marrow U-MRD4 in patients with R/R CLL. Responses were durable, including in patients with high-risk genomics.
Publisher: American Association for Cancer Research
Keywords: Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/pathology/mortality/genetics; *Sulfonamides/administration & dosage/adverse effects/therapeutic use; Aged; Middle Aged; Piperidines/administration & dosage/therapeutic use/adverse effects; Female; Male; *Adenine/analogs & derivatives/administration & dosage/therapeutic use; *Bridged Bicyclo Compounds, Heterocyclic/administration & dosage/adverse; effects/therapeutic use; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; Neoplasm Recurrence, Local/drug therapy; Treatment Outcome
Department(s): Haematology
Publisher's Version: https://doi.org/10.1158/2643-3230.Bcd-25-0345
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-03-02 05:02:25

Last Modified: 2026-05-21 11:17:47