Pneumonitis After Immune Checkpoint Inhibitor Therapies in Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study

Authors

Ajay Sheshadri
Alberto A Goizueta
Vickie R Shannon
David London
Guillermo Garcia-Manero
Hagop M Kantarjian
Farhad Ravandi-Kashani
Tapan M Kadia
Marina Y Konopleva
Courtney D DiNardo
Sherry Pierce
Abdulrazzak Zarifa
Aya A Albittar
Linda L Zhong
Fechukwu O Akhmedzhanov
Muhammad H Arain
Mansour Alfayez
Ahmad Alotaibi
Mehmet Altan
Aung Naing
Tito R Mendoza
Myrna C B Godoy
Girish Shroff
Sang T Kim
Saadia A Faiz
Dimitrios P Kontoyiannis
Fareed Khawaja
Kristofer Jennings
Naval G Daver

Publication Date

7-15-2022

Journal

Cancer

Abstract

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were modeled as a time-dependent variable and incorporated a standard risk set modifying variables into the models.

Results: Thirty patients developed pneumonitis (12%). Of these, 17 had partial or complete resolution, whereas 13 patients died from pneumonitis. Increasing age (hazard ratio [HR], 1.04 per year; 95% confidence interval [CI], 1.00-1.08), and baseline shortness of breath increased pneumonitis risk (HR, 2.51; 95% CI, 1.13-5.55). Female sex (HR, 0.33; 95% CI, 0.15-0.70) and increasing platelet count (HR, 0.52 per log-unit increase; 95% CI, 0.30-0.92) decreased pneumonitis risk. In adjusted models, ICI-related pneumonitis significantly increased mortality (HR, 2.84; 95% CI, 1.84-4.37).

Conclusions: ICI-related pneumonitis occurs at a high rate in AML patients and increases mortality.

Lay summary: Immune checkpoint inhibitors (ICIs) remove inhibitory signals that reduce T-cell function and allow T-cells to better attack cancer cells. In acute myeloid leukemia (AML), the effectiveness of ICIs is limited in part by inflammation of the lung, called pneumonitis. This study reviewed 258 patients with AML who received ICIs and identified 30 patients who developed pneumonitis, nearly half of whom died. Older age and baseline shortness of breath increased pneumonitis risk, whereas female sex and higher baseline platelet counts decreased pneumonitis risk. Pneumonitis increased mortality by nearly 3-fold. This work highlights the significant harm imposed by pneumonitis after ICI therapies.

Keywords

Antineoplastic Agents, Immunological, Dyspnea, Female, Humans, Immune Checkpoint Inhibitors, Leukemia, Myeloid, Acute, Lung Neoplasms, Pneumonia, Retrospective Studies, immune checkpoint inhibitor, pneumonitis, acute myeloid leukemia, hypomethylating agent, mortality

DOI

10.1002/cncr.34229

PMID

35452134

PMCID

PMC9232977

PubMedCentral® Posted Date

7-15-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes