Objectives: Multi-agent chemotherapy including bleomycin, doxorubicin, dacarbazine, and vinblastine has been the standard of care for initial treatment of Hodgkin Lymphoma (HL) for over 40 y. The study objective was to estimate the rate of new pulmonary events in HL patients exposed to bleomycin.
Methods: A retrospective cohort study supplemented by chart abstraction included newly diagnosed adult HL patients from the US DOD military healthcare system between 1/1/2005 and 12/31/2013 and followed until death, disenrollment on 6/30/2016. Patients with concurrent primary malignancies and those receiving <2 chemotherapy agents as first-line treatment were excluded. Pulmonary events (pulmonary fibrosis, pneumonitis, interstitial lung disease, pneumonia, bronchiolitis obliterans, acute respiratory distress syndrome) after exposure to bleomycin ± RT were identified through ICD-9/10 codes from the electronic medical records. Logistic regression and Cox proportional hazards models were developed to identify predictors of the first new pulmonary event and time to a new event.
Results: A total of 642 HL patients were identified, mean age (SD) of 32 y (13.0), 67% male, 35% stage 3/4 at diagnosis. Bleomycin was administered to 85.8% of patients, and 30% of these experienced new pulmonary events. For those treated with bleomycin, 9.4% experienced new pulmonary events up to 6 months after exposure and an additional 13.8% between 7-24 months and 5.1% between 24-48 months after bleomycin exposure. Logistic regression and Cox proportional hazards model fit results were modest. Significant predictors were age and number of doses of bleomycin; however, pulmonary events could not be predicted by the number of bleomycin doses received since the probability peaked after 4 doses.
Conclusions: This analysis demonstrates that HL patients may experience a new pulmonary event up to 2 y after receiving initial treatment containing bleomycin. The incidence of pulmonary events associated with bleomycin was difficult to predict in this patient population .