C77-48 Clinical Effectiveness of Immunomodulatory Therapies for Steroid-Dependent Immune Checkpoint Inhibitor Pneumonitis: A Multicenter Retrospective Analysis

Rationale

Immune checkpoint inhibitors (ICIs) have improved cancer-related mortality in multiple solid tumor malignancies. ICI pneumonitis (ICI-p) is an immune-mediated adverse effect that causes treatment-related morbidity and mortality. While corticosteroids are the mainstay of treatment, a subset of patients develop recurrent lung injury with tapering of steroids (steroid-dependent ICI-p), resulting in extended steroid use, steroid-related adverse effects, and delays in cancer treatment. Though society guidelines recommend several steroid-sparing options, clinical efficacy data for these agents are limited.

Methods

We conducted a multicenter retrospective cohort study at three large academic medical centers evaluating patients with steroid-dependent ICI-p. Inclusion criteria consisted of cancer patients who developed ICI-p with recurrent pneumonitis during steroid taper. Demographic variables, pneumonitis severity (CTCAE grading), pneumonitis resolution (symptomatic and radiographic resolution achieved with a steroid dose equivalent to prednisone </=10 mg daily) and overall survival (OS) were recorded. For each therapeutic option, patient demographic and clinical characteristics were compared between those who received the treatment (Yes) and those who did not (No). In addition, OS was compared between these two groups using the Kaplan-Meier method.

Results

Fifty-seven patients with steroid-dependent ICI-p were identified. Twenty-nine (50.9%) received infliximab, 13 (22.8%) mycophenolate, 13 (22.8%) intravenous immunoglobulin (IVIG), 10 (17.5%) tocilizumab, 1 (1.8%) cyclophosphamide, and 1 (1.8%) rituximab; six patients were treated with more than one steroid-sparing therapeutic . Patients receiving IVIG had a higher proportion of lung cancer (61.5% vs. 25%, p = 0.021) and prior chest radiation (53.8% vs. 11.4%, p = 0.003). The time from pneumonitis diagnosis to steroid initiation was shorter among patients who received infliximab compared with those who did not. When comparing one therapeutic option to the others, there was no difference in pneumonitis severity or pneumonitis resolution between the treatment groups, though pneumonitis resolution was lower with IVIG (30.8% vs 69.2%, p = 0.03). Lower OS was observed among patients who received IVIG compared to those who did not (median 0.82 vs. 31.1 months, p = 0.03).

Conclusions

Infliximab, mycophenolate, and tocilizumab demonstrated equivocal efficacy for steroid-dependent ICI-p, though significant differences in treated tumor types and days from pneumonitis diagnosis to steroid initiation were identified. IVIG was associated with lower resolution rates and worse OS, potentially confounded by underlying lung cancer and prior chest radiation. Larger longitudinal studies are needed to determine optimal choice and timing of steroid-sparing treatment for steroid-dependent ICI-p.

This abstract is funded by: None