Research Reveals Common Types of Rituximab-Induced Interstitial Lung Disease in Patients With Lymphoma

Rituximab-induced interstitial lung disease (RILD) in patients with non-Hodgkin lymphoma (NHL) presents most commonly as lung disease, organizing pneumonia, and nonspecific interstitial pneumonia, and it is associated with 179 pathogenic microorganisms, according to a retrospective study in the Annals of Hematology.¹

“These findings enhance the understanding of RILD in patients with non-Hodgkin lymphoma and serve as a reference for best management guidelines in these patients,” the authors wrote.

Researchers performed chest high-resolution CT to evaluate the extent, distribution, and radiologic patterns of interstitial lung disease in 321 patients. | Image Credit: © meeboonstudio - stock.adobe.com

The study is the first to systematically characterize RILD in patients with NHL according to bronchoalveolar lavage (BAL) findings and treatment course of RILD, according to the authors.

Researchers performed chest high-resolution CT (HRCT) to evaluate the extent, distribution, and radiologic patterns of the disease in 321 patients who developed RILD between 2020 and 2022.

More than three-quarters of patients (79.8%) were diagnosed with diffuse large B-cell lymphoma. The remaining patients had the following: marginal zone lymphoma (10.9%); follicular lymphoma (2.5%); Burkitt lymphoma (2.2%); mantle cell lymphoma (2.2%); high-grade B-cell lymphoma (1.5%); chronic lymphocytic leukemia/small lymphocytic lymphoma (0.9%). The chemotherapy regimen was resiniferatoxin (RTX) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in all patients.

BAL was performed in 299 patients to analyze cellular distribution and identify pathogens using metagenomic next-generation sequencing. The remaining patients could not undergo bronchoscopy because of severe clinical symptoms. Radiological and bronchoscopic BAL findings revealed infectious lung disease in 123 patients and noninfectious lung disease in 198 patients.

After multidisciplinary team discussions of the histological results, it was determined that 27 patients had drug-induced ILD, 9 patients had lymphoma infiltrating the lungs, 6 patients had fungal infections, and 3 patients had
Mycobacterium tuberculosis infections. Among the 27 patients with drug-induced ILD, pathological examination showed 10 patients with organizing pneumonia, 5 patients with nonspecific interstitial pneumonia, 5 patients with hypersensitivity pneumonitis, and 3 patients with eosinophilic pneumonia.

Of the 217 patients who underwent metagenomic next-generation sequencing, 179 pathogenic microorganisms were detected, including bacteria (77), viruses (45), Pneumocystis jirovecii strains (28), fungi (17), M tuberculosis (6), and atypical pathogens (6).

All patients received combination therapy. Cyclophosphamide, doxorubicin, vincristine, and prednisone were the most commonly administered regimens. The median time from treatment to RILD development was 1.7 months.

Patients were classified as having RILD if both rituximab for NHL and ILD were present. ILD was defined as diffuse interstitial lung infiltrates detected on chest HRCT. Patients were excluded if they had any of the following: known congenital lung disease; mental or cognitive impairment; use of other new anti-tumor drugs; severe comorbidities such as severe pulmonary infection, severe heart disease, or liver and kidney dysfunction, which could interfere with research results; patients receiving radiation therapy; and incomplete case or simultaneous participation in other clinical studies.

Slightly more than half (58.9%) the patients were male, and the median patient age was 48 years (range, 17–78 years).

This year, an estimated 20,140 patients will die of NHL, comprising 3.3% of all US cancer deaths, according to the National Cancer Institute.²

“The clinical, histopathological, and radiological characteristics of ILD and secondary diseases, as well as those of infectious and non-infectious pneumonia of this type, overlap considerably,” the authors stated.¹ “Therefore, understanding the clinical characteristics of RILD and its active prevention and treatment is essential for patients undergoing immunochemotherapy.”

References

1. Zou W, Zhang J, Li Y, et al. Interstitial lung disease presents with varying characteristics in patients with non-Hodgkin lymphoma undergoing rituximab containing therapies. Ann Hematol. Published online September 25, 2024. doi:10.1007/s00277-024-06013-2
2. Cancer stat facts: non-Hodgkin lymphoma. Accessed October 9, 2024. National Cancer Institute. https://seer.cancer.gov/statfacts/html/nhl.html