Interstitial Lung Disease in Patients with Diffuse Large B-Cell Lymphoma Receiving CHOP-Based Chemotherapy Is Associated with the Use of Rituximab.

Background: Several cases of chemotherapy-induced interstitial lung disease (ILD) or pneumonitis have been reported in recent years in patients with lymphoma. The potential roles of rituximab (R) and granulocyte colony stimulating factor (GCSF), agents more commonly used in recent years, are suggested.

Objective: We wanted to determine the prevalence of ILD and identify risk factors in patients with diffuse large B-cell lymphoma (DLCL) who received cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP)-based chemotherapy.

Methods: Selection criteria included newly diagnosed DLCL patients treated at our institution from 2000–2006 who received CHOP with or without R and had at least 3 serial CT or PET/CT scans during chemotherapy. ILD was defined as new bilateral interstitial pulmonary infiltrates not likely representing fluid overload or fibrosis. One radiologist blinded to clinical data reviewed all imaging studies.

Results: Out of a total of 174 new cases of DLCL, 73 met our study criteria. Reasons for exclusion included no chemotherapy (45), <3 imaging studies (46), and non-CHOP-based chemotherapy (10). Among the 73 study patients, 52 (71%) received R in addition to CHOP. Eleven (15.1%) patients developed ILD, all in the subgroup that received RCHOP (P = 0.027). Most occurred between cycles 2 and 4 of RCHOP (81.8%) and persisted until after completion of chemotherapy (63.6%). Nine (81.8%) patients with ILD were asymptomatic and never required treatment or delay of RCHOP. The remaining 2 patients became symptomatic (1 hospitalized), were empirically treated for atypical pneumonia with clinical recovery, and had delay of RCHOP. All patients received the intended number of courses of RCHOP. Univariate analysis of potential ILD risk factors among those who received RCHOP showed a trend with the subgroup that either had GCSF or cardiopulmonary disease (P = 0.09). Multivariate analysis using a two-variable model suggests that the use of GCSF or presence of cardiopulmonary disease (P = 0.065) and a high (3–5) international prognostic index score (P = 0.13) need further investigation as risk factors.

Conclusions: In our cohort of DLCL patients receiving CHOP-based chemotherapy, ILD was common and significantly associated with the use of R. While most cases were asymptomatic, self-limited, and did not require delay of chemotherapy, more serious presentation could occur. The mechanism of ILD is unknown and requires further investigation.