Nivolumab increases pulmonary artery pressure in patients treated for non-small cell lung cancer
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ORIGINAL ARTICLE
Nivolumab increases pulmonary artery pressure in patients treated for non‑small cell lung cancer Ludovic Fournel1,2 · Pascaline Boudou‑Rouquette2,3 · Mathilde Prieto1 · Remi Hervochon4 · Claude Guinet4 · Jennifer Arrondeau2,3 · Jérôme Alexandre2,3 · Diane Damotte2,5 · Marie Wislez2,6 · Frédéric Batteux2,7 · Philippe Icard1,8 · François Goldwasser2,3 · Marco Alifano1,2 Received: 8 June 2020 / Accepted: 6 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD). Methods We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated. Results 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1. Conclusion Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition. Keywords Nivolumab · Immune check-point inhibitors · Pulmonary artery hypertension · Lung cancer
* Ludovic Fournel [email protected] 1
Thoracic Surgery Department, Cochin Hospital, APHP.Center-University of Paris, 27 rue du Faubourg Saint‑Jacques, 75014 Paris, France
Immunomodulatory Therapies Multidisciplinary Study Group (CERTIM), Cochin Hospital, AP-HP.Center-University of Paris, Paris, France
2
3
Oncology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France
4
Radiology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France
5
Pathology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France
6
Respiratory Medicine and Thoracic Oncology Department, Cochin Hospital, AP-HP.Center-University of Paris, Paris, France
7
Biology and Immunology Depar
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