How would you treat a patient with end-stage lung cGVHD and worsening hypoxia? Free

We asked, and you answered! Here are the responses from this month’s “You Make the Call” question about treating a patient with end-stage lung cGVHD and worsening hypoxia.

Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.

Is there a role of the combined use of ruxolitinib and belumosudil? 

Yes, there are data for the combined use of ruxolitinib and belumosudil, recently published as abstracts by Chin et al. at the 2022 American Society of Hematology (ASH) annual meeting and Iskra et al. at the 2023 European Society for Blood and Marrow Transplantation (EBMT) annual meeting (accepted for presentation in April 2023). The response rate with this combined modality for cGVHD of the lung ranged from 11% (n=2/19) to 20% (n=1/5). Although the sample sizes were small, there seems to be some efficacy noted. These two drugs, which were recently approved by the U.S. Food and Drug Administration (FDA), have different mechanisms of action and tolerable safety profiles.^1,2 Prospective studies are needed to validate these findings.  

Is there a suggestion for a different treatment regimen for lung cGVHD? 

This patient seems to have exhausted most of the conventional treatment options for cGVHD of the lung. Other conventional secondary therapies like sirolimus, mycophenolate mofetil, and IL-2 based therapy, which have an overall response rate of 76%, 26-64%, and 52%, respectively, could also be considered for steroid-refractory cGVHD based on retrospective cohort and phase II studies.^3,4 However, data on their efficacy with steroid-refractory cGVHD of the lung are limited, highlighting an unmet need for these patients.  

Clinical trials are also an option. Abatacept, a newer drug that selectively modulates T-cell activation, was recently approved for the prevention of acute GVHD and has shown promising efficacy in cGVHD of the lung in retrospective analysis.⁵ In this study, patients with bronchiolitis obliterans showed significant clinical improvement and durable responses following treatment with abatacept, with a response rate of 89% based on improvement in lung severity score (n=6), stabilized lung function (n=4), or both (n=3). 

Another newer drug is axatilimab, which is a colony-stimulating factor 1 receptor (CSF-1 R) antibody that showed a partial response of 40% in patients with cGVHD of the lung who had failed two or more lines of therapy.⁶  

Is there a role for lung transplant with severe lung cGVHD? 

There is a role for lung transplant in cGVHD of the lung on a case-by-case basis. Lung transplantation outcomes following allogeneic hematopoietic cell transplant (alloHCT) were comparable to other end-stage diseases.⁷ Lung transplantation less than two years after alloHCT increased all-cause one-year mortality (hazard ratio = 7.5, 95% CI 2.3-23.8; p=0.001). This patient, who is 10 years out from his alloHCT, should be evaluated for possible lung transplant.⁸  

Akash Mukherjee, MD
Cesar Gentille Sanchez, MD
Muthu Veeraputhiran, MD
Little Rock, AR

References 

1. Chin M, Shizuru JA, Muffly L, et al. Belumosudil combination therapy in refractory chronic graft-versus-host disease. Blood. 2022;140(Supplement 1):4788-4789.
2. Iskra et al. Belumosudil and ruxolutinib combination therapy for treatment of steroid-refractory chronic graft-versus-host disease. To be presented at the 2023 European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting; April 2023; Paris, France.
3. Flowers MED, Martin PJ. How we treat chronic graft versus host disease. Blood. 2015;125(4):606-615.
4. Wolff D, Fatobene G, Rocha V, Kröger N4, Flowers ME. Steroid-refractory chronic graft-versus-host disease: treatment options and patient management. Bone Marrow Transplant. 2021;56(9):2079-2087.
5. Wertheimer T, Dohse M, Afram G, et al. Abatacept as salvage therapy in chronic graft-versus-host disease—a retrospective analysis. Ann Hematol. 2021;100(3):779-787.
6. Kitko CL, Arora M, DeFilipp Z, et al. Axatilimab for chronic graft-versus-host disease after failure of at least two prior systemic therapies: results of a phase I/II study [published online, 2022 Dec 2]. J Clin Oncol. doi: 10.1200/JCO.22.00958.
7. Greer M, Berastegui C, Jaksch P, et al. Lung transplantation after allogeneic stem cell transplantation: a pan-European experience. Eur Respir J. 2018;51(2):1701330.
8. Koenecke C, Hertenstein B, Schetelig J, et al. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT. Am J Transplant. 2010;10(8):1897-1906.