Deborah M. Stephens, DO, on CLL/SLL: NCCN Clinical Practice Guidelines in Oncology® Update

Deborah M. Stephens: In the presentation, I reviewed treatment options and how to select these options in the frontline and subsequent treatment settings for patients with CLL. In the frontline setting, critical decision points are based on the molecular features of IGHV status, TP53 mutation status, and presence or absence of deletion 17p and medical comorbidities. These decision points are still critical in the subsequent treatment setting. However, this setting adds some key dynamics of evaluating prior lines of therapy and understanding if the patient was resistant or intolerant to the prior therapy. Notably, the regimens are similar in the frontline and subsequent treatment setting, including second-generation BTK inhibitors of acalabrutinib and zanubrutinib, or the Bcl-2 inhibitor Venetoclax plus CD20, a monoclonal antibody. The patients with CLL who may be appropriate for Venetoclax-based therapies are those with a history of uncontrolled atrial fibrillation or hypertension, or patients who have need for systemic anticoagulation, or those who desire time-limited therapy. The patients with CLL who may be appropriate for BTK inhibitor therapy are those with renal insufficiency, extensive infections excluding aspergillosis, or those without access to facilities to monitor for tumorlysis syndrome. In the NCCN guidelines last year, the BTK inhibitor ibrutinib was moved to the other recommended category from the preferred category. This is due to the results of two large phase-three studies the elevate RR and the Alpine study, which compared acalabrutinib or zanubrutinib head-to-head with ibrutinib in patients with relapsed CLL. In these trials, acalabrutinib and zanubrutinib demonstrated equal or better efficacy and less toxicity, making the second-generation BTK inhibitors the preferred choice. In patients who have developed resistance to BTK inhibitor therapy, a novel BTK inhibitor called pertobrutinib is emerging as an efficacious option with minimal toxicity. This drug has not yet been approved for CLL, but it was approved for mantle cell lymphoma. In summary, there are multiple highly effective therapies for patients with CLL, and continued refinement of the active drugs has resulted in improved toxicity and hopefully better quality of life for the patients with chronic lymphocytic leukemia.