Doubling Down for Durable Remission in Chronic Lymphocytic Leukemia

Front-line therapy with ibrutinib–venetoclax has been shown to outperform standard chemotherapy — fludarabine, cyclophosphamide, and rituximab (FCR) — in patients with chronic lymphocytic leukemia (CLL). Now, investigators report long-term outcomes among nearly 900 patients with previously untreated CLL and no del(17p) who were randomized to receive ibrutinib–venetoclax, ibrutinib alone, or FCR. The ibrutinib-containing regimens were continued for up to 6 years unless toxicity or progression occurred or the patient qualified for treatment discontinuation based on undetectable measurable residual disease (MRD) in bone marrow.

Key results were as follows:

• Undetectable MRD at 2 years was significantly more common with ibrutinib–venetoclax (66%) than with ibrutinib alone (0%) or FCR (48%).
• During a median follow-up of 62 months, patients receiving ibrutinib–venetoclax had significantly better outcomes than those receiving ibrutinib alone or FCR:
  • 5-year progression-free survival (94% vs. 79% vs. 58%)
  • Disease progression or death (7% vs. 22% vs. 43%)
  • 5-year overall survival (96% vs. 90% vs. 86%)
• In subgroup analyses, patients with unmutated immunoglobulin heavy-chain variable region (IGHV) appeared to benefit from ibrutinib–venetoclax more than those with mutated IGHV.
• Febrile neutropenia was more frequent with FCR; atrial fibrillation and hypertension were more common with ibrutinib-containing regimens.