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Women demonstrated more favorable outcomes in CLL
Female sex was associated with improved survival and more favorable prognostic factors in chronic lymphocytic leukemia, according to results of a study review.
The analysis included 1,821 patients with Binet stages A progressive, B or C untreated CLL enrolled in four randomized trials conducted between 1978 and 2004, and 1,299 patients with Binet stage A CLL enrolled in three prospective studies conducted between 1978 and 1998.
The population included more men in both the randomized series (73%) and registration series (59%). More women than men were aged older than 70 years in the randomized series (34% vs. 28%) and registration series (44% vs. 36%).
Women in the randomized trials were more likely to have Binet stage A progressive disease than stage B or C disease, and those in the registration series were more likely to have Rai stage 0 CLL than stage I or II disease.
Overall, results showed significantly prolonged OS among women in the randomized trials (HR=0.72; 95% CI, 0.64-.81) and in the registration series (HR=0.71; 95% CI, 0.62-0.81).
More women than men achieved 10-year OS in the randomized trials (27% vs. 15%; P=.0001) and in the registration series (55% vs. 43%; P˂.0001).
The overall response rates were higher among women vs. men (83% vs. 71%; P˂.0001). However, fewer women received the full treatment dose (79% vs. 85%; P=.01), and more women experienced any toxicity (85% vs. 78%; P=.01) and gastrointestinal toxicity (57% vs. 42%; P˂.0001).
Women were more likely to have favorable prognostic features, such as low beta-2 microglobulin mutated IGHV, absence of TP53 abnormalities and/or 11q deletion, and CD38 and Zap-70 negativity.
“It should be recognized that CLL has a more benign clinical course in women than in men,” the researchers wrote. “Women may require modification in the dosage of the more intensive therapies, as it appears that the thresholds for both efficacy and gastrointestinal toxicity may be lower in women. The increase in male:female ratio from monoclonal B-cell lymphocytosis, through early stage CLL, to CLL requiring treatment shows that the more active, aggressive forms of CLL are seen predominantly in men and new therapeutic targets should focus on that finding.”
Disclosure: The researchers report no relevant financial disclosures.
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Recent major interest in manipulating T lymphocytes to destroy B lymphocytes in chronic lymphocytic leukemia and acute lymphoblastic leukemia may provide insight into these findings. Prolactin powerfully affects T-lymphocyte function, underlying its hypothesized role in understanding the disparate prevalence of autoimmune diseases, such as lupus, in females. Not only does prolactin stimulate T-cell function, but prolactin’s receptor on these cells is specifically blocked by the immunosuppressant cyclosporine. The findings in this article may reflect female hormone (eg, prolactin?) stimulation of T-cell killing of CLL-malignant B cells.