Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited- duration therapy.

Abstract

We report long-term follow-up of the phase 1b study of venetoclax and rituximab (VenR) in patients with relapsed chronic lymphocytic leukemia (CLL), including outcomes with continuous or limited-duration therapy. Patients received venetoclax daily (200-600 mg) and rituximab over 6 months and then received venetoclax monotherapy. Patients achieving complete response (CR), CR with incomplete marrow recovery (CRi), or undetectable minimal residual disease (uMRD) assessed by flow cytometry (<10-4 cutoff) were allowed, but not required, to discontinue therapy, while remaining in the study and could be retreated with VenR upon progression. Median follow-up for all patients (N = 49) was 5.3 years. Five-year rates (95% CI) for overall survival, progression-free survival, and duration of response were 86% (72-94), 56% (40-70), and 58% (40-73), respectively. Of the 33 deep responders (CR/CRi or uMRD), 14 remained on venetoclax monotherapy (continuous therapy), and 19 stopped venetoclax therapy (limited-duration therapy) after a median of 1.4 years. Five-year estimates of ongoing response were similar between continuous (71%; 95% CI, 39-88) or limited-duration therapy (79% [49-93]). Six of 19 patients in the latter group had subsequent disease progression, all >2 years off venetoclax (range, 2.1-6.4). Four patients were retreated with VenR, with partial responses observed in the 3 evaluable to date. VenR induced deep responses that were highly durable with either continuous or limited-duration therapy. Retreatment with VenR induced responses in patients with CLL progression after discontinuing therapy. Continuous exposure to venetoclax in deep responders does not appear to provide incremental benefit.

• Authors: Shuo Ma, John F Seymour, Danielle M Brander, Thomas J Kipps, Michael Y Choi, Mary Ann Anderson, Kathryn Humphrey, Abdullah Al Masud, John Pesko, Ruby Nandam, Ahmed Hamed Salem, Brenda Chyla, Jennifer Arzt, Amanda Jacobson, Su Young Kim, Andrew W Roberts
• Journal: Blood (Blood) Vol. 138 Issue 10 Pg. 836-846 (09 09 2021) ISSN: 1528-0020 [Electronic] United States
• PMID: 34115103 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Sulfonamides
• Rituximab
• venetoclax

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Bridged Bicyclo Compounds, Heterocyclic (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, mortality)
• Male
• Middle Aged
• Recurrence
• Rituximab (administration & dosage, adverse effects)
• Sulfonamides (administration & dosage, adverse effects)
• Survival Rate