Comorbidities and Sex Differences in Causes of Death Among Mantle Cell Lymphoma Patients - A Nationwide Population-Based Cohort Study

Abstract

Background: The prognosis for mantle cell lymphoma (MCL) remains poor, particularly for elderly patients. Our aim was to assess the impact of comorbidities on MCL outcome and causes of death. Methods: For all 1,385 MCL patients (1,009 males, 376 females) diagnosed 2000-2014 in Sweden (median age 71 years, range 22-96) comorbidities within 10 years prior to diagnosis were classified according to the Charlson comorbidity index (CCI; 0, 1, 2+). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using flexible parametric models to compare rates of lymphoma-specific and all-cause-mortality by comorbidities. Model-based predictions were used to obtain probabilities of death from lymphoma/other causes. Findings: Severe comorbidity was independently associated with higher all-cause (HR=1·52; 95% CI:1·24-1·85) and lymphoma-specific mortality (HR=1·.31; 95% CI:1·04-1·65), particularly among patients with connective tissue, renal, psychiatric diseases, and dementia. 606 patients (44%) had any comorbidity (CCI 1+) and 388 (28%) severe comorbidity (CCI 2+). Over a median follow-up of 3.7 years (range 0-16), 633 patients (46%) died, the majority (76%) from their lymphoma. Among females with comorbidities, non-lymphoma deaths represented a larger proportion of all deaths, as compared to comorbid males. Interpretation: Since most MCL patients (including comorbid patients) died from lymphoma, more efficient and tolerable lymphoma treatments need to be considered also to patients with severe comorbidity. Patients with renal, psychiatric, or connective tissue disorders need particular attention. However, among females with comorbidities, the likelihood of dying from disorders other than MCL was still considerable, perhaps favoring a more liberal use of a wait-and-watch approach. Funding Statement: This study was supported by the Swedish Cancer Society CAN (2012/774). I. Glimelius was supported by The Swedish Cancer Society (CAN 2016/440) and the Swedish Society of Medicine. Declaration of Interests: MJ: Honoraria from Janssen, Gilead, Celgene, Roche, Acerta. Research support from Janssen, Celgene, Abbvie and Gilead. KES: Honoraria from Celgene. Research support from Janssen. IG Honoraria from Janssen. SE has an ongoing role as project manager in a publicprivate real world evidence collaboration between Karolinska Institutet and Janssen Pharmaceuticals NV (contract: 5-63/2015) Ethics Approval Statement: The study was approved by the Regional Board of the Ethical Committee in Stockholm, Sweden (2007/1335-31/4, 2010/1624-32).