Review Outlines Treatment Sequencing for Relapsed or Refractory CLL/SLL

A review in the Journal of Clinical Oncology discusses contemporary management of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). As frontline targeted therapies expand, subsequent treatment selection requires assessment of clinical status, prior therapy, progression kinetics, and possible Richter transformation. The authors also emphasize genomic re-evaluation, particularly for acquired resistance mutations and TP53 aberrations.

The review describes second-generation covalent BTK inhibitors acalabrutinib and zanubrutinib as providing durable disease control with improved tolerability over ibrutinib. Other options include continuous venetoclax monotherapy or fixed-duration venetoclax–rituximab, with venetoclax retreatment feasible in selected patients. The noncovalent BTK inhibitor pirtobrutinib offers activity after prior covalent BTK inhibitor exposure. For heavily pretreated patients, the review highlights lisocabtagene maraleucel; allogeneic hematopoietic cell transplantation remains an option for selected patients with double-class refractory disease.

Treatment sequencing should account for disease biology, depth and duration of previous response, comorbidities, toxicity, patient preferences, and logistical constraints. BTK degraders, next-generation BCL2 inhibitors, and bispecific antibodies are identified as emerging approaches. The available abstract provides no quantitative efficacy or safety estimates or detailed evidence appraisal, limiting comparisons among strategies. Individualized planning and clinical trial participation remain central themes.