In treatment-naïve patients with chronic lymphocytic leukemia (CLL) and those with relapsed/refractory (R/R) CLL, sequential treatment with bendamustine debulking followed by obinutuzumab and idelalisib was associated with durable responses and undetectable minimal residual disease (MRD) levels, according to results from the CLL2-BCG trial presented at the 62nd American Society of Hematology Annual Meeting & Exposition.
Results from the open-label, multicenter CLL2-BCG trial were presented by Paula Cramer of the University Hospital in Cologne. The trial enrolled 48 patients with high-risk CLL who had an absolute lymphocyte count of 25,000/µl or more and/or lymph nodes measuring 5 cm or greater.
The investigators administered two cycles of bendamustine 70 mg/m² as debulking (n=38). During the induction phase, patients received obinutuzumab 1,000 mg on days one, eight, and 15 of cycle one and day one of cycles two through six (n=33). Twice-daily idelalisib 150 mg was added to this obinutuzumab regimen in cycle two. The investigators continued to administer daily idelalisib in addition to obinutuzumab every three months during the maintenance phase until patients achieved an MRD-negative complete response for up to 24 months (n=27).
The median age of the population was 66 years. A total of 16 patients were treatment-naïve, and 32 had experienced R/R CLL after a median of two prior lines of therapy.
Overall response rates in the full analysis set and the per-protocol analysis were 80% and 85%, respectively. Approximately 23% of patients in the full analysis and 27% of patients in the per-protocol analysis achieved undetectable MRD levels. The median progression-free survival was 44 months in treatment-naïve patients and 33 months in R/R CLL patients. Although the median overall survival (OS) was not reached for treatment-naïve patients, the median OS was 46 months in patients with R/R disease.
There was a total of 603 adverse events reported in the overall cohort, with 52% of events related to the study drug. Deaths occurring in this study were due to infections (n=7), cardiac arrest (n=1), and Richter’s transformation (n=1).
“In light of the current, alternative therapeutic options, the BCG [trial] regimen … should be used with caution,” the authors noted, “but represents an alternative treatment option if ibrutinib and venetoclax have failed.”