How to sequence agents for steroid-refractory chronic GvHD

During the GvHD Hub Steering Committee meeting, key opinion leaders met to discuss how to sequence agents for steroid-refractory chronic GvHD. This recorded discussion was chaired by Mohamad Mohty, and featured Hildegard Greinix, Yi-Bin Chen, Attilio Olivieri, Mutlu Arat, Arnon Nagler, Florent Malard, Bipin Savani, and Ali Bazarbachi.

The members considered a case study presented by Mohamad Mohty and discussed their management strategies for this patient, weighing up the efficacy of alternative treatments. This case study is outlined in Figure 1.

Figure 1. Case study outline 

aGvHD, acute GvHD; allo-HSCT, allogenic hematopoietic stem cell transplantation; AML, acute myeloid leukemia; cGvHD, chronic GvHD; CR1, complete response.

Treatment options

There are multiple appropriate treatments for this case, one being ruxolitinib due to its benefits in mucosal cGvHD as well its use to accelerate the tapering of previous steroid treatment. Extracorporeal photopheresis (ECP) may also be considered, with recent clinical data suggesting ECP is particularly effective in skin and oral presentations of GvHD. A combination therapy of ruxolitinib and ECP has also been shown to be effective in this group and can serve to faster taper steroids. The most appropriate drug or combination (Figure 2) can be determined by the risk of relapse and any other individual considerations for the patient.

Figure 2. Treatment options for cutaneous mucosal presentations of steroid-refractory chronic GvHD 

Case scenario variations

Certain variations to the case presentation may influence the management options. For example, ibrutinib is an alternative that may be considered for patients, particularly those with B-cell malignancies; however, other than in this specific patient group, ibrutinib is a lower priority option due to its reduced efficacy and higher toxicity in comparison with ruxolitinib.

In the case of cytopenia and cytomegalovirus reactivation, ECP would be more appropriate. Furthermore, the addition of moderate lung involvement to this scenario would indicate alternative treatments such as belumosudil, which has a slightly higher overall response rate in lung manifestations of cGvHD compared with ruxolitinib.¹

Conclusion

Multiple options are available for the treatment of patients with steroid-refractory cGvHD. The most appropriate management strategies depend on the individual presentation of the patient, in particular the organ manifestations present and may include a singular therapy or a combination treatment regimen.