The use of renin-angiotensin-aldosterone system (RAAS) inhibitors may reduce the onset of bleomycin-induced lung injury (BLI), according to study findings published in Clinical Lymphoma, Myeloma & Leukemia. In addition, the results also showed that older age and history of hypertension were independent risk factors for the development of BLI.

Researchers from Japan evaluated the data of 190 patients (median age 38 years) who had received treatment at the Tokai University Hospital and the Ebina General Hospital from 2004 to 2018 with a regimen containing intravenous bleomycin. More than half (54.2%) of the cases were Hodgkin lymphoma, which was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

The other 87 cases were of patients with germ cell tumors: testicular (24.2%), ovarian (16.8%), and mediastinal (4.7%). Almost all of these patients were treated with bleomycin, etoposide, and cisplatin (BEP). Two were treated with vinblastine, bleomycin, cisplatin, etoposide, and doxorubicin.


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Patients also received granulocyte-colony stimulating factor (52.1%) and radiation therapy (21.1%).

At baseline, 31 patients were found to have the following comorbidities: hypertension (16.3%), bronchial asthma (7/4%), heart failure and/or arrhythmia (3.2%), and chronic obstructive pulmonary disease (1.1%).

The incidence of BLI was the primary endpoint of the retrospective analysis, with a secondary endpoint of death caused by BLI.

Study findings showed 21 (11.1%) cases of symptomatic BLI, with 17 of those patients being treated with ABVD and 4 with BEP. A lower dose of bleomycin was associated with the development of BLI, the researchers noted. The median cumulative bleomycin dosage was 120 mg (range, 44-270 mg) in the BLI-onset group and 180 mg (range, 10-450 mg) in the no-BLI group.

Significantly more cases of BLI were seen in patients who were aged 63.5 years and older. Previous hypertension was also a significant risk factor.

The relationship between patient prognosis and significant BLI risk factors were investigated by dividing the patients into 4 groups: no risk factors (140 patients), younger than 65 years with hypertension (17), 65 years and older with no hypertension (19), and both hypertension and older age (14). BLI occurred in 5, 2, 6, and 8 cases, respectively (P <.001). Zero deaths occurred in the no risk factor group. However, 1 death occurred in the hypertension group, 2 in the older age group, and 6 in the group with both risk factors (P <.001).

In a separate analysis, 31 cases with hypertension were studied. BLI incidence was 12.5% in patients administered RAAS inhibitors compared with 53.3% in those not treated with the group of drugs.

To improve prognosis in older patients and those with hypertension, healthcare providers should apply an initial treatment strategy other than bleomycin, the researchers concluded. Moreover, they noted, prophylactic use of RAAS inhibitors may help to complete bleomycin treatment more safely in patients with these risk factors.

Reference

Hara R, Onizuka M, Shiraiwa S, et al. The role of hypertension and renin-angiotensin-aldosterone system inhibitors in bleomycin-induced lung injury. Clinical Lymphoma, Myeloma & Leukemia. Published online October 8, 2020. doi:10.1016/j.clml.2020.10.004