Pre-Existing Heart Failure Tied to Higher Mortality in Lymphoma

Patients with diffuse large B-cell lymphoma (DLBCL) and pre-existing heart failure (HF) were less likely to receive standard -- but cardiotoxic -- anthracycline treatment, likely resulting in worse survival outcomes, according to a longitudinal cohort study using Medicare data.

HF at diagnosis was present in 14% of the 30,000 DLBCL patients in the study, and multivariable analysis showed this group had a 45% lower odds of receiving anthracyclines in the first year after diagnosis (OR 0.55, 95% CI 0.49-0.61), reported researchers led by Jenica Upshaw, MD, MS, of Tufts Medical Center in Boston.

Furthermore, few patients (7%) with pre-existing HF who received an anthracycline were managed with cardioprotective strategies, such as the use of dexrazoxane or liposomal doxorubicin.

As described in JAMA Cardiology, pre-existing HF was associated with higher cardiovascular mortality (HR 1.82, 95% CI 1.65-2.00) and lymphoma-specific mortality, with HRs for the latter ranging from 1.24 (95% CI 1.18-1.31) to 1.36 (95% CI 1.29-1.43) in various models that adjusted for clinical, hospital-level, and treatment variables.

"Our findings underscore the need for close collaboration between cardiology and oncology to ensure optimal guideline-directed medical therapy of all cardiac comorbidities and cardiac risk factors to improve lymphoma and cardiovascular outcomes," the researchers wrote.

At 1 and 5 years, cardiovascular and lymphoma-specific mortality were far higher for the subset with pre-existing HF:

• Cardiovascular mortality at 1 year: 7.5% vs 2.8% for the subset without HF
• Cardiovascular mortality at 5 years: 13.4% vs 6.4%, respectively
• Lymphoma-specific mortality at 1 year: 41.8% vs 29.6%
• Lymphoma-specific mortality at 5 years: 51.6% vs 40.1%

Those death rates are "eye-opening," said Ana Barac, MD, PhD, of Inova Heart and Vascular Institute in Falls Church, Virginia, in a commentary accompanying the study, adding that the results are "an awakening call to the cardio-oncology field to give needed attention to patients with HF and different malignancies."

"One of the novel contributions of this study is the detailed investigation of prescribed lymphoma treatment, showing how patients with pre-existing HF were half as likely to be treated with anthracyclines compared with patients without HF," Barac continued. "The findings are not unexpected, as anthracycline use is avoided to decrease HF risk; however, they provide a sobering perspective of the unmet need in patients with pre-existing HF and DLBCL."

The researchers used data from the Surveillance, Epidemiology, and End Results–Medicare registry from 1999 to 2016 to capture pre-existing HF in DLBCL patients. The study included 30,728 individuals (mean age 77.8, evenly split between men and women) with newly diagnosed DLBCL from 2000 to 2015. All patients had Medicare Part A or B continuously in the year prior to their lymphoma diagnosis.

Among the total study population, 48.4% received anthracycline-based chemotherapy in the first year after their lymphoma diagnosis, 20.5% received non-anthracycline chemotherapy, and 31.0% received no chemotherapy. Anthracyclines (either doxorubicin or liposomal doxorubicin) were used for 26.2% of patients with pre-existing HF and 54% of those without pre-existing HF.

"Future randomized trials are needed to understand whether targeted cardioprotection with dexrazoxane or liposomal formulation in addition to optimized guideline-directed HF therapy can reduce lymphoma and cardiovascular mortality in this high-risk patient population," the researchers wrote. They noted that many hospitals have now created cardio-oncology programs "with the goal of providing cardiology care that is informed by the patient's oncologic treatment with multidisciplinary collaboration to optimize oncologic and cardiovascular outcomes."

Limitations to the study, the investigators said, include that the results may not be applicable to younger patients. Also, in the time since the study period, there have been additional medications shown to reduce morbidity and mortality in patients with HF.

In addition, because HF, comorbidities, and cancer treatments were ascertained using claims data, the team did not have access to specific clinical data and thus could not categorize HF more specifically. Furthermore, although claims for doxorubicin allow for the determination of the number of cycles, it was not possible to know if there were dose reductions or if the doxorubicin was given as a continuous infusion.

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