Elderly Patient Management and Real-World Evidence in CLL

Dr. Shadman notes that discussions about elderly patients with CLL increasingly focus on patients aged 80 years and older, given the disease's median diagnosis age of 68 to 70 years. The SEQUOIA study team conducted a focused analysis of patients aged 80 years and older receiving zanubrutinib, which Dr. Lipsky reviews.

Regarding efficacy, older patients respond equivalently to younger patients. From a safety standpoint, grade 3 adverse events in this cohort didn't reveal unexpected signals compared to the overall CLL population. Infections remain the primary concern across CLL therapy and occur predominantly in the first 6 months, likely reflecting disease activity rather than being purely treatment-related. The 72-month PFS for patients aged 80 and older was approximately 63.8%, indicating that a substantial proportion of octogenarians will require subsequent lines of therapy.

Dr. Lipsky emphasizes that the assumption patients aged 80 and older require only one line of therapy is incorrect; real-world Flatiron data showed approximately half of patients aged 75 to 79 years needed a subsequent therapy during follow-up, and approximately one-third of those aged 80 years and older also required additional treatment.

Dr. Shadman then addresses real-world evidence comparing BTKis, referencing a Medicare database analysis comparing zanubrutinib, acalabrutinib, and ibrutinib that demonstrated an efficacy advantage for zanubrutinib over both comparators. He contextualizes this as consistent with the broader trend of accumulating evidence supporting zanubrutinib efficacy, while acknowledging these indirect comparisons serve as confirmatory data points rather than definitive evidence, since he rarely relies on real-world evidence alone in clinical practice.