The New England Journal of MedicineTime-Limited Initial Therapy for Young, Fit Patients with CLL

In the phase III GAIA–CLL13 study, researchers investigated time-limited treatment options for fit patients with chronic lymphocytic leukemia (CLL) and a low burden of coexisting conditions. The study compared the efficacy of chemoimmunotherapy with venetoclax-obinutuzumab, both with and without ibrutinib. The results showed that the venetoclax-based regimens were superior to chemoimmunotherapy in terms of achieving undetectable minimal residual disease and longer progression-free survival (PFS). The percentages of patients with undetectable minimal residual disease were remarkably high, with 86.5% in the venetoclax-obinutuzumab group and 92.2% in the venetoclax-obinutuzumab-ibrutinib group, among the highest reported in first-line treatment for CLL.

The study confirmed the significant prognostic value of undetectable minimal residual disease at the end of time-limited treatment, as it translated into superior PFS. The study emphasized the need for treatment options for fit CLL patients with normal renal function, as data from prospective, randomized clinical studies evaluating the safety and efficacy of venetoclax-obinutuzumab in this specific patient population were lacking. The study demonstrated that the venetoclax-obinutuzumab-ibrutinib combination had a higher incidence of tumor lysis syndrome compared to venetoclax-ibrutinib, likely due to the simultaneous administration of obinutuzumab with ibrutinib, leading to rapid depletion of CLL cells. The findings highlight the importance of continuing to develop therapeutic strategies to achieve a cure for CLL patients.

Note: The study was previously presented in part at the ASH 2021 Annual Meeting and the EHA 2022 Congress.