Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions

Handunnetti, SM; Anderson, MA; Burbury, K; Thompson, PA; Burke, G; Bressel, M; Di Iulio, J; Hicks, RJ; Westerman, D; Lade, S; Pott, C; Agarwal, R; Koldej, R; Ritchie, D; Dreyling, M; Dawson, MA; Dawson, SJ; Seymour, JF; Roberts, AW; Tam, CS

Author(s): Handunnetti, SM; Anderson, MA; Burbury, K; Thompson, PA; Burke, G; Bressel, M; Di Iulio, J; Hicks, RJ; Westerman, D; Lade, S; Pott, C; Agarwal, R; Koldej, R; Ritchie, D; Dreyling, M; Dawson, MA; Dawson, SJ; Seymour, JF; Roberts, AW; Tam, CS;
Details: Publication Year 2024-08-22,Volume 144,Issue #8,Page 867-872
Journal Title: Blood
Publication Type: Research article
Abstract: In the phase 2 clinical trial (AIM) of venetoclax-ibrutinib, 24 patients with mantle cell lymphoma (MCL; 23 with relapsed/refractory [R/R] disease) received ibrutinib 560 mg and venetoclax 400 mg both once daily. High complete remission (CR) and measurable residual disease negative (MRD-negative) CR rates were previously reported. With median survivor follow-up now exceeding 7 years, we report long-term results. Treatment was initially continuous, with elective treatment interruption (ETI) allowed after protocol amendment for patients in MRD-negative CR. For R/R MCL, the estimated 7-year progression-free survival (PFS) was 30% (95% confidence interval [CI], 14-49; median, 28 months; 95% CI, 13-82) and overall survival (OS) was 43% (95% CI, 23-62; median, 32 months; 95% CI, 15 to not evaluable). Eight patients in MRD-negative CR entered ETI for a median of 58 months (95% CI, 37-79), with 4 experiencing disease recurrence. Two of 3 reattained CR on retreatment. Time-to-treatment failure (TTF), which excluded progression in ETI for those reattaining response, was 39% overall and 68% at 7 years for responders. Beyond 56 weeks, grade ≥3 and serious adverse events were uncommon. Newly emergent or increasing cardiovascular toxicity were not observed beyond 56 weeks. We demonstrate long-term durable responses and acceptable toxicity profile of venetoclax-ibrutinib in R/R MCL and show feasibility of treatment interruption while maintaining ongoing disease control. This trial was registered at www.clinicaltrials.gov as #NCT02471391.
Publisher: American Society of Hematology
Keywords: Humans; *Lymphoma, Mantle-Cell/drug therapy/mortality; *Sulfonamides/administration & dosage/therapeutic use/adverse effects; *Bridged Bicyclo Compounds, Heterocyclic/administration & dosage/adverse; effects/therapeutic use; Male; Female; Aged; Middle Aged; *Adenine/analogs & derivatives/administration & dosage; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse; effects/administration & dosage; *Piperidines/administration & dosage/adverse effects/therapeutic use; Aged, 80 and over; Remission Induction; Treatment Outcome; Adult; Follow-Up Studies; Disease-Free Survival
Department(s): Clinical Haematology; Pathology; Office of Cancer Research
Publisher's Version: https://doi.org/10.1182/blood.2023023388
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-12 06:49:04

Last Modified: 2024-09-12 06:49:36