News|Articles|March 23, 2026

CLL/SLL Treatment Choices Based on Various Factors

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Key Takeaways

Time-limited venetoclax–obinutuzumab was the predominant first-line regimen, while continuous BTK inhibitor therapy remained nearly as common, and chemoimmunotherapy was rarely selected.
Enrichment for BTK inhibitor selection occurred in del(17p)/TP53-mutated disease (84%), indicating adverse-risk biology strongly influences real-world first-line strategy.
Geographic access shaped therapy; living >100 km from an obinutuzumab-capable center increased BTK inhibitor use, highlighting infusion logistics as a structural determinant.
Older patients (>75 years) disproportionately chose BTK inhibitors, with appointment burden and convenience frequently cited over traditional fitness or comorbidity indices.
Shared decision-making appeared inconsistent, as more than one therapeutic option was documented in only 64% of cases, suggesting potential gaps in preference-sensitive care delivery.

Patients with chronic or small lymphocytic leukemia now have a variety of treatment options, although a new report found not every patient was presented with multiple options.

Disease characteristics, age, and geography are among the main factors that shape first-line treatment patterns in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL), according to a new study of real-world therapeutic decision-making.

The findings, which were reported in the European Journal of Haematology, are based on a population-based study of patients in Alberta, Canada.¹

Investigators noted that the armamentarium for CLL/SLL has evolved in recent years. Continuous Bruton tyrosine kinase (BTK) inhibitor therapy and time-limited regimens pairing the BCL-2 inhibitor venetoclax (Venclexta; AbbVie) with the CD20-directed antibody obinutuzumab (Gazyva; Genentech), the first-generation BTK inhibitor ibrutinib (Imbruvica; Pharmacyclics/Janssen Biotech), or the second-generation BTK inhibitor acalabrutinib (Calquence; AstraZeneca) have become the standard first-line options for patients.²

The investigators said a relative lack of head-to-head trials until recently has led patients and clinicians to make treatment choices based largely on individual factors; however, the factors influencing those decisions have not been well-defined. They decided to analyze the treatment choices of a consecutive series of 148 adult patients with a median age of 71 who began treatment for CLL/SLL in the province of Alberta during calendar year 2024. The authors wanted to find out which treatments were being chosen and which factors—if any—correlated with those choices.

They found that the most common therapeutic choice was time-limited venetoclax plus obinutuzumab (Ven-O), which was chosen by 73 patients (51%). Another 65 patients (44%) chose continuous BTK inhibitor therapy. Of the remaining 10 patients, 8 chose chemotherapy-based regimens and 2 chose time-limited ibrutinib plus venetoclax.

When the authors looked at the 138 patients who chose either continuous BTK inhibitor therapy or time-limited Ven-O, they found that patients with deletion of 17p (del[17p]) or TP53 mutations preferred BTK inhibitor therapy over Ven-O (84% vs 16%; P = .0002), as did patients older than 75 years (66% vs 34%; P = .0051) and those who lived more than 100 km from a cancer center that could initiate obinutuzumab (70% vs 30%; P = .031).

Other factors, including sex, having CLL vs SLL, treatment center, Charlson Comorbidity Index scores, cardiovascular comorbidities, and IGHV mutation status were not significantly associated with treatment choice, the investigators found.

Although the study was framed as an analysis of treatment choices, the investigators found that many patients did not appear to have been given multiple treatment options. They said discussions of more than 1 therapeutic option were documented in only two-thirds of cases (94 cases; 64%). In these 94 cases in which clinicians noted the reasons for the therapeutic choice, the preference for a time-limited therapy was listed as the key factor in 35 cases, followed by logistical considerations (28 cases), perceived toxicity differences (20 cases), adverse-risk genomic factors (20 cases), and patient fitness or frailty (13 cases), the investigators reported.

When the investigators looked at specific subgroups, they found adverse-risk genetics was the key factor affecting treatment decisions among most patients with del(17p)/TP53 mutation (15 of 19 patients). Among patients older than 75 years, appointment burden and logistical convenience were the key considerations in 13 of 29 patients. Similarly, 11 of 14 patients living more than 100 km from a cancer center said logistics were their most important factor.

The investigators said their findings offer a window into the real-world decisions of patients with CLL/SLL, showing that a variety of factors can affect treatment choices.

“These findings highlight the importance of personalized care and the need to reduce access barriers to time-limited strategies and optimize real-world treatment decision-making,” the authors concluded.

References

Tidswell R, Owen C, Shafey M, et al. Real-world selection of venetoclax-obinutuzumab versus BTK inhibitor therapy for treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma. Eur J Haematol. Published online February 16, 2026. doi:10.1111/ejh.70137
Walewska R, Eyre TA, Bloor A, et al. 2025 British Society for Haematology Guideline for the treatment of chronic lymphocytic leukaemia. Br J Haematol. 2025;207(6):2296-2313. doi:10.1111/bjh.70100