Sequential therapy with bendamustine followed by obinutuzumab plus venetoclax may be safe and highly effective in patients with chronic lymphocytic leukemia (CLL), according to a study published in The Lancet Oncology.
Previous studies have shown the effectiveness of venetoclax alone or in combination with the anti-CD20 antibody rituximab in CLL. Combining venetoclax with obinutuzumab, an even more potent anti-CD20 antibody, may further improve the depth of response and outcomes while diminishing adverse events (AEs).
For the ongoing phase 2 CLL2-BAG trial, researchers enrolled 66 patients with CLL and a relevant tumor load (absolute lymphocyte count 25,000 or more cells/μL or lymph nodes with a diameter at least 5 cm), and assigned them to 2 debulking cycles with bendamustine followed by 6 cycles of induction and 24 cycles of maintenance therapy with obinutuzumab and venetoclax. Eligible patients had ECOG performance status of 0 to 3. The median follow-up was 16 months.
By the end of induction, the overall response rate (ORR) among all efficacy-evaluable patients was 95% (P =.0002), including 5 patients with complete response and 55 with partial responses. All treatment-naive patients and 26 (90%) of 29 patients with relapsed or refractory (R/R) disease had an overall response. Minimum residual disease (MRD) was achieved in 87% and 83% of treatment-naive and R/R patients, respectively.
The most frequently reported grade 3 to 4 AEs observed during both debulking and induction included neutropenia, thrombocytopenia, and infection. The safety profile of the regimen has remained consistent with previous reports of its individual components, and only 3 cases of tumor lysis syndrome were observed.
Results show that combination therapy with venetoclax and obinutuzumab may be among the most effective treatment options available for patients with CLL, with ORR and MRD rates comparing favorably with current first-line therapies. The authors concluded however, that “until data from these trials with higher patient numbers are available, the use of venetoclax combined with obinutuzumab in routine practice cannot be recommended, especially in the first-line setting.”
Cramer P, von Tresckow J, Bahlo J, et al. Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label, phase 2 trial [published online August 13, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30414-5