Published in The New England Journal of Medicine, findings from the investigator-initiated phase 3 CLL17 randomized trial demonstrate that limited duration targeted therapy for chronic lymphocytic leukemia (CLL) can be as effective as continuous treatment.
This study included 909 patients with previously untreated CLL who were randomly assigned to receive continuous therapy with ibrutinib, maintained indefinitely over time, or fixed-duration venetoclax-based therapy. Results showed that fixed-duration treatment was as effective as continuous ibrutinib with regard to progression-free survival.
CLL is the most frequent chronic leukemia and it affects B lymphocytes, a type of white blood cell. This disease is significantly more common in adults, particularly older adults. The evolution of the disease is variable. Thus, in many cases patients are asymptomatic at diagnosis and do not require immediate treatment but instead undergo a period of active surveillance. In contrast, more than 60% of patients will require treatment during the course of disease. Nowadays there are several effective treatments that can control CLL while maintaining a good quality of life for patients.
Fixed-duration vs. continuous treatment
Thanks to a better understanding of disease biology, several targeted treatments have been developed for CLL. Initially, these therapies were administered as maintenance therapy until disease progression. Subsequently, new strategies combining fixed-duration targeted therapies showed great antitumor activity while reducing the toxicity of the drugs. This present study was designed to establish whether fixed-duration strategies are as effective as continuous treatments.
“Fixed-duration strategies offer advantages such as therapy-free intervals and a possible reduction in long-term toxicity, although there was uncertainty as to whether they could be as effective as continuous treatments,” said Francesc Bosch, Head of the Vall d’Hebron University Hospital’s Hematology Service, Group Leader of Experimental Hematology at VHIO, and a CLL17 Trial Investigator on behalf of the Spanish Chronic Lymphocytic Leukemia Group (GELLC).
“Since targeted therapies were approved head-to-head versus chemotherapy, direct evidence comparing the two treatment approaches was lacking. This present study was designed to prospectively evaluate the efficacy of continuous ibrutinib treatment versus fixed-duration venetoclax–obinutuzumab or venetoclax–ibrutinib in previously untreated patients with chronic lymphocytic leukemia.”
After a median follow-up of nearly three years, data showed that all three regimens were similarly effective at controlling the disease. At three years, approximately 80% of patients remained disease-free in all three groups, demonstrating that fixed-duration treatments are as effective as continuous therapy.
A particularly relevant finding is that, after the end of treatment, a much higher proportion of patients treated with the fixed-duration venetoclax combinations had no detectable disease in their blood: over 70% of the patients in the venetoclax-obinutuzumab group and almost 50% in the venetoclax-ibrutinib group, compared to none in the ibrutinib group. These results indicate deeper responses with limited-duration treatments.
Taken together, findings demonstrate that it is possible to treat this patient population effectively without the need for indefinite therapy, providing equally effective options with treatment-free intervals.
“This work provides strong evidence supporting a paradigm shift in the initial treatment of chronic lymphocytic leukemia, consolidating fixed-duration therapies as an effective, safe, and more flexible treatment option. Long-term follow-up will confirm the durability of responses and better define which patients benefit most from each specific treatment regimen,” concluded Bosch.
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Reference
Al-Sawaf O, Stumpf J, Zhang C, Simon F, Bosch F, Feyzi E, Ghia P, Gregor M, Kater AP, Lindström V, Mattsson M, Niemann CU, Staber PB, Tadmor T, Thornton P, Wendtner CM, Janssens A, Noesslinger T, Bohn JP, da Cunha-Bang C, Poulsen CB, Ranti J, Illmer T, Schoettker B, Böttcher S, Gaska T, Vandenberghe E, Clifford R, Benjamini O, Frustaci AM, Scarfò L, Sportoletti P, Schreurs J, Levin MD, van der Straaten H, van der Klift M, Tran H, de la Serna J, Loscertales J, Lindblad O, Bergendahl Sandstedt A, Goede J, Baumann M, Fink AM, Fischer K, Ritgen M, Kreuzer KA, Schneider C, Tausch E, Stilgenbauer S, Robrecht S, Eichhorst B, Hallek M; CLL17 Trial Investigators. Fixed-Duration versus Continuous Treatment for Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Dec 6. doi: 10.1056/NEJMoa2515458.
