Bleomycin Induced Lung Toxicity in Hodgkin Lymphoma Patients Treated with ABVD Regimen- a Single Center Experience from Riyadh, Saudi Arabia

Introduction:

Bleomycin is a glycopeptide antibiotic with antitumor activity that is included in the standard front-line chemotherapy regimen ABVD (Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine) for the treatment of Hodgkin's lymphoma (HL). While the ABVD regimen is very effective, one of the major concerns is the potential for pulmonary toxicity associated with bleomycin. Bleomycin-associated pneumonitis is observed in 1-3% of patients overall, and up to 20-30% of patients older than 60-65 years of age receiving ABVD (ASH-SAP, 2019). The mortality rate from bleomycin pulmonary toxicity has been reported to be as high as 4.2% and 24% in patients who developed the pulmonary syndrome (Martin et al, 2005). The Novel treatments such as BV-AVD (Brentuximab vedotin, Doxorubicin, Vinblastine, and Dacarbazine) (Connors et al., 2018) and N-AVD (Nivolumab plus Doxorubicin, Vinblastine, and Dacarbazine) (Rutherford et al., 2023) was associated with significantly lower pulmonary toxicity compared to ABVD. There is limited data about incidence and outcomes of bleomycin toxicity from middle eastern region and we aim to study the same in this group of population.

Method

This is a retrospective study conducted in a tertiary center at King Fahad medical City, Riyadh, Saudi Arabia. All patients with Hodgkin's lymphoma treated with a bleomycin-based chemotherapy (Jan 2016 to May 2024) were included. Patient received 1-12 standard doses of Bleomycin depending on stage and response.

Results

401 successive patients treated with the ABVD chemotherapy regimen were evaluated for Bleomycin pulmonary toxicity (BPT). BPT was observed in 16 patients (4%) within the study population (13 patient below 60 years and 3 patients over 60 years). The median age of affected patients was 33 years (range 17-79), with 17% being over the age of 60. Two patients (12%) were active smokers. The majority of affected patients (64%) required mechanical ventilation, and one patient required non-invasive ventilation. Four patients (23%) showed a response to steroid therapy with no residual lung findings. The median time to development of BPT was 15 weeks from the start of ABVD treatment. Seven patients (41%) received granulocyte colony-stimulating factor during ABVD therapy. The number of bleomycin doses received ranged from 1 to 12 doses, with 10 patients (59%) receiving more than 4 doses (median of 5 doses).

There were 7 deaths (44% of affected patients), thus representing overall mortality of 1.8% of overall patients treated with ABVD. 5 patients (29% of affected patients) were younger than 60 years. The median overall survival of the affected patients with BPT is 17 months

Conclusion

This analysis highlights the significant risk of bleomycin-induced pulmonary toxicity, including the associated mortality risk including young patients with no previous lung disease or smoking history, observed within our patient cohort receiving the ABVD regimen. Our results are similar to what is reported in literature although more younger patients affected including some deaths. HL has an excellent long-term outlook, but bleomycin has rare but substantial toxicity including death, and with availability of better alternative regimens based on Brentuximab or Nivolumab, we recommend using alternative regimens based on the results of this study in order to reduce this unpredictable toxicity with no effective treatment.

No relevant conflicts of interest to declare.