The Evolving Landscape of First-Line CLL Therapy
For patients with chronic lymphocytic leukaemia (CLL), the shift from chemoimmunotherapy to targeted agents has fundamentally transformed the standard of care. Currently, combinations involving Bruton’s tyrosine kinase (BTK) inhibitors and B-cell lymphoma 2 (BCL2) inhibitors represent the vanguard of treatment. Triplet regimens—incorporating a BTK inhibitor, a BCL2 inhibitor, and an anti-CD20 monoclonal antibody—have demonstrated exceptional efficacy in achieving deep, durable remissions. However, the high potency of these triplets often comes at the cost of increased hematological toxicity and a higher incidence of infections.
The HOVON 158/NEXT STEP trial addresses a critical question in clinical oncology: Can we achieve the efficacy of a triplet regimen while minimizing toxicity through a tailored, response-adaptive approach? By using measurable residual disease (MRD) as a biological compass, the study explored whether intensification should be reserved only for those who fail to reach deep remission after an initial doublet therapy.
