The combination of ibrutinib and venetoclax may be effective for treating patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) due to the complementary mechanisms of action of the two targeted therapies.
Ibrutinib mobilizes CLL cells from the lymph nodes and inhibits cancer cell proliferation while venetoclax kills any circulating cancer cells.
The GLOW study is the first randomised clinical trial to investigate the efficacy and safety of ibrutinib + venetoclax (I+V) as a first-line fixed-duration oral treatment compared with chlorambucil + obinutuzumab (Clb+O) for untreated CLL/SLL.
A total of 211 patients were recruited and randomized 1:1 with a median follow-up of 27.7 months.
Patients treated with I+V showed significantly improved progression-free survival compared with those treated with Clb+O, which was consistent across all predefined subgroups. Furthermore, the rate of undetectable minimal residual disease (uMRD) in both bone marrow and peripheral blood was also significantly higher in the I+V arm 3 months after the end of treatment.
Importantly, 84.5% of patients in this group maintained uMRD in peripheral blood at 12 months after treatment conclusion.
Similarly, I+V achieved higher complete response rates and prolonged the time to subsequent therapy. Common grade ≥3 treatment-emergent adverse events were neutropenia (34.9%), diarrhea (10.4%), and hypertension (7.5%) for I+V.
Taken together, I+V as a first-line treatment for CLL/SLL demonstrated superior efficacy compared with Clb+O with improved depth and duration of remission and tolerable safety profile.