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Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study


Franzen, Daniel; Schad, Karin; Kowalski, Benedikt; Clarenbach, Christian F; Stupp, Roger; Dummer, Reinhard; Kohler, Malcolm (2018). Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study. Cancer Immunology, Immunotherapy, 67(1):127-134.

Abstract

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of ≥ 10%, or ≥ 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean ± SD DLCO decreased significantly during follow-up (-4.3% ± 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.

Abstract

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of ≥ 10%, or ≥ 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean ± SD DLCO decreased significantly during follow-up (-4.3% ± 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Drug toxicity; Ipilimumab; Metastatic melanoma; Pneumonitis
Language:English
Date:2018
Deposited On:01 Dec 2017 16:31
Last Modified:20 Feb 2018 08:57
Publisher:Springer
ISSN:0340-7004
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s00262-017-2071-2
PubMed ID:28983773

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