Mapping comorbidity in chronic lymphocytic leukemia: impact of individual comorbidities on treatment, mortality, and causes of death


Comorbid conditions are highly prevalent in chronic lymphocytic leukemia (CLL), nevertheless, detailed information on the association of specific comorbidities with CLL prognosis is missing. Using Danish, nation-wide registers, we followed consecutive patients from CLL-diagnosis in 1997–2018, until death or end of follow-up. Sub-grouping of comorbidities was defined using a modified Charlson comorbidity index. Patients were matched on sex, date of birth (±1 month), and region of residency with up to ten comparators from the general population. In total, 9170 patients with CLL were included in the study, with a median of 5.0 years of follow-up. All comorbid conditions studied were individually associated with increased mortality, and many also with increased cause-specific mortality, related or unrelated to CLL. Comorbidity correlated with increased mortality from infections and cardiovascular disease. CLL patients, particularly older, had a significant loss of lifetime compared with the general population. This study highlights a large subgroup of comorbid CLL patients with an unmet treatment-need and missing efficacy and safety data on treatment, who are under-prioritized in clinical trials. Also, studies assessing interventions that may provide better tolerability of treatment in older or comorbid patients, with cancer in general, and CLL in particular, are warranted.

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Fig. 1: Association between individual comorbidities and all-cause mortality and cause-specific mortality among CLL patients.
Fig. 2: Causes of death for CLL patients who are non-comorbid, comorbid, or multimorbid.
Fig. 3: Overall survival (OS) for patients with CLL compared with matched comparators from the general population stratified on comorbidity and age.


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This study was supported in part by grants from Novo Nordisk Foundation grant NNF16OC0019302 and AstraZeneca to CUN and Neye Fonden to HHJ. AstraZeneca was provided with the opportunity to prospectively review the manuscript. The funding sources had no role in the study design, collection, analysis, or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication.

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ECR and KR conducted the data management and analyzed the data. ECR and HF wrote the first draft of the paper. All authors contributed to the study concept and design, writing of the manuscript, and approved the final paper.

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Correspondence to Emelie Curovic Rotbain.

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Conflict of interest

ECR received consultancy fees or travel grants from Abbvie, Janssen, and AstraZeneca. HF received support outside this work from Alexion, Gilead, Abbvie, Janssen Pharmaceuticals, and Novartis. CC-B received consultancy fees and/or travel grants from Abbvie, and Gilead. CUN received support from Novo Nordisk Foundation NNF16OC0019302 and AstraZeneca within this work. CUN received support, consultancy fees, or travel grants from Abbvie, Gilead, Janssen, Roche, CSL Behring, Acerta, Genmab, Sunesis, and Astra Zeneca outside this work. HHJ received support from Neye Fonden outside this work. KR reports no conflicts of interest.

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Rotbain, E.C., Niemann, C.U., Rostgaard, K. et al. Mapping comorbidity in chronic lymphocytic leukemia: impact of individual comorbidities on treatment, mortality, and causes of death. Leukemia (2021).

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