Fixed-duration or continuous treatment for CLL?

Two established treatment paradigms for patients with previously untreated chronic lymphocytic leukaemia (CLL) went head-to-head in a large, randomised trial. The results provided clear guidance for haematologists on therapy selection for their patients with CLL.

“Continuous treatment with a Bruton’s tyrosine kinase (BTK) inhibitor or fixed-duration therapy with a B-cell lymphoma 2 (BCL2) inhibitor plus a CD20 monoclonal antibody or a BTK inhibitor are 2 established treatment strategies in CLL,” explained Dr Othman Al-Sawaf (University Hospital of Cologne, Germany) [1]. “These treatment options have, however, not been compared directly in a randomised study.” The CLL17 trial (NCT04608318) enrolled 909 participants with previously untreated CLL, randomising them 1:1:1 to continuous therapy with ibrutinib, fixed-duration therapy with venetoclax plus obinutuzumab, or fixed-duration therapy with venetoclax plus ibrutinib. The primary objective was to assess whether fixed-duration therapy was non-inferior to continuous BTK inhibition with respect to progression-free survival (PFS).

After a median follow-up of 34.2 months, the overall response rates were similar across arms, ranging from 84% for the venetoclax-obinutuzumab to 88% for the venetoclax-ibrutinib, with the continuous ibrutinib demonstrating an 86% response rate. “The complete response rates were higher with fixed-duration therapy (51.5% and 46.2% vs 8.3%),” noted Dr Al-Sawaf. The 3-year PFS rates were 81.1% for venetoclax-obinutuzumab, 79.4% for venetoclax-ibrutinib, and 81.0% for continuous ibrutinib, meeting the non-inferiority criteria. “This result was consistent across immunoglobulin heavy-chain variable region (IGHV) status, tumour protein 53 (TP53)-mutation status, and fitness,” he added.

Regarding safety, neutropenia occurred more frequently in the venetoclax-obinutuzumab arm (52.5%) than in the venetoclax-ibrutinib (36.3%) or the continuous ibrutinib (16.4%) arms. Atrial fibrillation was most common with continuous ibrutinib (16.8%), compared with 12.5% in the venetoclax-ibrutinib arm and 3.7% in the venetoclax-obinutuzumab arm. Infection rates were high across all therapies (around 80%), although grade 3–5 infections were more prevalent in the venetoclax-obinutuzumab arm (34.9%) than in the venetoclax-ibrutinib (25.1%) or the continuous ibrutinib (24.8%) arms.

“This study showed that fixed-duration targeted therapy is non-inferior to continuous BTK inhibitor therapy with respect to PFS,” concluded Dr Al-Sawaf. “For most patients with previously untreated CLL, fixed-duration therapy should therefore be the primary option.”

1. Al-Sawaf O, et al. Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: results from the randomized CLL17 trial. Abstract 1, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

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Posted on 22 December 202522 December 2025