Ibrutinib Plus Rituximab Demonstrates Efficacy as Second-Line Treatment for Patients With CLL and R/R AIHA/PRCA

Results from a Phase 2 Multicenter Trial

Findings from a phase 2 multicenter trial published in Leukemia indicated that ibrutinib plus rituximab yielded efficacy as a second-line treatment for patients with chronic lymphocytic leukemia (CLL) and relapsed/refractory (R/R) autoimmune cytopenias (AICs), such as autoimmune hemolytic anemia (AIHA) and pure red aplasia (PRCA). 

Autoimmune cytopenias occur in 5% to 10% of patients with CLL, and “can significantly complicate the management of CLL, worsen the quality of life, and sometimes can be fatal,” stated Eugene Nikitin, MD, Moscow City Clinical Hospital, Moscow, Russian Federation, and coauthors, adding “The optimal treatment of steroid refractory AIHA/PRCA is not well established.”

This multicenter study assessed the efficacy and safety of Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in combination with rituximab for patients with R/R to steroids AIHA/PRCA and CLL. The primary end point was the overall response at each visit during the first 6 months and at the end of the induction phase, as well as the duration of response, among patients with R/R CLL, AIHA, and PRCA. Secondary end points included time to treatment failure, CLL progression, toxicity, time to best response, safety, and overall survival. 

The study protocol involved an induction phase consisting of the administration of ibrutinib at 420 mg daily alongside rituximab weekly for 8 weeks, followed by 4 monthly infusions. The maintenance phase consisted of ibrutinib monotherapy continuation until disease progression or until intolerable toxicity was observed. 

A total of 50 patients were enrolled in this study, including 44 with warm AIHA, 2 with cold AIHA, and 4 with PRCA. Following the induction phase, 74% of patients (n = 34) achieved a complete response and 21.7% (n = 10) achieved a partial response. The median time to hemoglobin normalization was 85 days. Notably, when evaluating CLL responses, 19% of patients (n = 9) achieved complete response, while 78% (n = 39) achieved partial remission. The median follow-up duration was about 37.56 months. 

In the AIHA group, 2 patients relapsed. In the PRCA group, 1 patient displayed no response, and another patient experienced a relapse following an initial achievement of complete response. The  remaining 2 patients maintained a complete response. The most prevalent adverse events were neutropenia (62%), infections (72%), and gastrointestinal complications (54%). 

Dr Nikitin et al concluded, “ibrutinib in combination with rituximab is an active second-line treatment option for patients with relapsed or refractory AIHA/PRCA and underlying CLL.”

Source: 

Nikitin E, Kislova M, Morozov D, et al. Ibrutinib in combination with rituximab is highly effective in treatment of chronic lymphocytic leukemia patients with steroid refractory and relapsed autoimmune cytopenias. Leukemia 37, 1464–1473. Published online May 18, 2023. doi: 10.1038/s41375-023-01891-3