Gender-Specific Approaches to CLL Care May Improve QOL Outcomes

Personalized support based on gender may be helpful for patients with chronic lymphocytic leukemia (CLL), according to a new study published in the European Journal of Haematology.¹ The research highlights gender differences in health-related quality of life (QOL) among patients with CLL.

The cross-sectional survey, led by researchers at the University of Haifa and collaborating institutions, enrolled 210 Israeli patients with CLL to compare outcomes between those under active surveillance and those receiving targeted therapies, specifically Bruton tyrosine kinase inhibitors (BTKi) or venetoclax-based regimens. The study found that men in surveillance generally reported better QOL than men receiving targeted therapies, whereas the reverse was true for women, who fared better while on treatment.

When CLL treatment types were compared, BTKi recipients reported better social/family well-being than those under surveillance. In contrast, venetoclax recipients reported lower physical well-being than the surveillance group. | Image credit: Kay Abrahams - stock.adobe.com

QOL was measured using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionnaire, measuring physical, social/family, emotional, and functional well-being (FACT-G), along with leukemia-specific symptoms and concerns (Leu subscale). Of the respondents, 63 were in surveillance, 115 were on active treatment (71 on BTKi, 44 on venetoclax-based regimens), and 32 had completed treatment. Women comprised 60.3% of the surveillance group but only 46.1% of the active treatment group.

When analyzed without sex stratification, the surveillance group reported better physical well-being than the treatment group (mean score, 22.8 vs. 20.5; P = .017), but lower social/family well-being (19.0 vs 22.1; P = .002). However, stratification revealed that among men, surveillance was associated with significantly higher scores in physical well-being (25.2 vs 19.7; P < .001), leukemia-specific concerns (51.5 vs 42.8; P = .002), and total FACT-Leu score (135.9 vs 120.5; P = .02).

​​For women, the pattern was reversed. Those receiving active treatment reported higher scores in social/family well-being (22.5 vs 18.9; P = .008), emotional well-being (18.2 vs 15.5; P = .003), FACT-G (83.3 vs 74.6; P = .009), and FACT-Leu (128.3 vs 116.7; P = .014), compared to those under surveillance. “Our findings suggest that women with CLL may require a more proactive and supportive approach during active surveillance periods compared to men,” the authors report.

The researchers also found, “a statistically significant interaction was observed between treatment group and sex in the emotional well-being subscale, where women reported higher QOL scores and men reported lower QOL scores in the active treatment group compared to the surveillance group.” The underlying causes, the authors suggest, may relate to both biological and psychosocial factors. While men tend to suppress emotional distress and may find the structured support of clinical follow-up during treatment unsettling, women often derive emotional and social benefits, as well as regain a sense of control, from the proactive engagement that active treatment provides.^2,3

When comparing differences within the surveillance group, men reported better scores than women across multiple domains, including physical and functional well-being (25.2 vs 21.2, P = .002 and 22.2 vs 19.1; P = .047, respectively) and leukemia-specific concerns (51.5 vs 42.1; P < .001). Conversely, in the active treatment group, women reported significantly better emotional well-being than men (18.2 vs 15.8; P = .009). “Sex is a crucial variable when comparing patients with CLL who are under active surveillance versus those receiving active treatment with targeted therapies,” researchers noted.

When treatment types were compared, BTKi recipients reported better social/family well-being than those under surveillance (22.3 vs 19; P = .003). In contrast, venetoclax recipients reported lower physical well-being than the surveillance group (19.6 vs 22.8; P = .03). This finding contradicts prior research, which has generally shown venetoclax to improve or at least not worsen quality of life, including physical well-being, compared with surveillance.^4,5 Patients who had completed treatment tended to report higher overall QOL, highlighting the potential benefits of time-limited regimens.

These findings indicate that sex should be considered in treatment decisions for CLL, with personalized support aimed at improving quality of life. The researchers stress that “By tailoring treatment and support strategies to the unique needs of each patient, health care providers can enhance QOL outcomes and promote more equitable care for individuals living with CLL.”

References

1. Mahameed B, Sharf G, Tadmor T, Kleinstern G. Gender disparities in health-related quality of life in patients with chronic lymphocytic leukemia: Impact of treatment modality. Eur J Haematol. 2025;0:1-9. doi:10.1111/ejh.70017

2. Arden-Close E, Absolom K, Greenfield DM, et al. Gender differences in self-reported late effects, quality of life and satisfaction with clinic in survivors of lymphoma. Psychooncology. 2011;20(11):1202-10. doi:10.1002/pon.1835

3. Trevino KM, Martin P, Chen Z, Leonard JP. Worsening quality of life in indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia patients in active surveillance: A 12-month longitudinal study. Clin Lymphoma Myeloma Leuk. 2022;22(2):82-88. doi:10.1016/j.clml.2021.08.001

4. Al-Sawaf O, Gentile B, Devine J, et al. Health-related quality of life with fixed-duration venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: Results from the randomized, phase 3 CLL14 trial. Am J Hematol. 2021;96(9):1112-1119. doi:10.1002/ajh.26260

5. Aw A, Banerji V, Bull SJ, et al. Quality of life in patients with chronic lymphocytic leukemia initiating venetoclax in routine clinical practice across Canada: Results from the Devote Study. Blood. 2022;140(suppl 1):12425-12426. doi:10.1182/blood-2022-156749