Mammalian target of rapamycin (mTOR)-induced pneumonitis: Single-institution experience and treatment.

Abstract

e13520 Background: Pulmonary toxicity is a class-effect associated with mTOR inhibitors. The aim of this assessment was to review the Cancer Therapy and Research Center (CTRC) experience with pulmonary toxicity of temsirolimus (T) and ridaforolimus (R), to characterize the drug-induced pneumonitis (DIP) associated with these agents, and to propose a management algorithm. Methods: A retrospective analysis of patients (pts) enrolled in any clinical trial using T or R at CTRC from 2001 to 2008 was performed. Pts were allowed to receive any formulation (IV/oral), dose or schedule of either drug. Pts from phase I studies whose endpoint was maximum tolerated dose were also included. Demographics, clinical and radiographic manifestation compatible with interstitial pneumonitis, DIP treatment, and response for each pt were recorded. Results: 199 pts were reviewed, 77 treated with T and 122 with R. 4 pts (5%) on T and 13 pts (11%) on R had findings compatible with DIP by CT imaging and pulmonology evaluation. These were described as interstitial infiltrates and/or ground glass opacities. Pathologic documentation in 3 pts was consistent with lymphocytic alveolitis/interstitial infiltrates. Two pts developed DIP after successive treatment with either drug, thus supporting the hypothesis of a class-effect. DIP resolved with drug interruption and a prednisone taper regimen 40mg qd ×7 days, then 20mg qd ×7 days, then 10mg qd ×14 days. No DIP-related death was recorded. Full-dose treatment with mTOR inhibitors was successfully resumed after resolution of radiologic and clinical abnormalities in 5 pts who had documented clinical benefit (CB= PR or SD>6mo). CB was documented in 2/4 pts (50%) and 9/13 pts (69%) with suspected T-and R-induced pulmonary toxicity, respectively. One pt had 3 episodes of reversible DIP while treated with R over 5+ years. Conclusions: This large, single institution, retrospective assessment demonstrates that mTOR induced pneumonitis is a class-effect, reversible with drug interruption and brief corticosteroid treatment. Therapy can usually be resumed following treatment of DIP. A better understanding of mTOR induced pneumonitis will be derived from randomized, controlled trials. No significant financial relationships to disclose.