Tandem Meetings 2026 | The current standard of care for GvHD prophylaxis in older patients undergoing transplantation

So, the standard of care right now is to utilize post-transplant cyclophosphamide. The standard dose, again, is at a double dose, so at 50 mg per kg on days 3 and 4, alongside calcineurin inhibitor and MMF. Really, this is because it’s been compared to CNI-based prophylaxis alone, and there were significant improvements in terms of clinically significant graft-versus-host disease. In other words, much lower clinically significant acute graft-versus-host disease and chronic graft-versus-host disease with post-transplant cyclophosphamide use. 

As I mentioned, while that was an improvement, what has also been seen on studies is compared to our old standard of care, there hasn’t been a demonstrated improvement in overall survival. And that could be for a number of reasons, one of which being, you know, while there is improvement in graft versus host disease control, overall transplant remains, you know, sort of a burdensome process, and so for that reason, there are sort of baked in morbidities that still exist, you know, particularly with post-transplant cyclophosphamide as well. But despite that, you know, with an equivalent survival, with better GVH control, you know, at least what we’re offering for patients with post-transplant cyclophosphamide is a better quality of life at one year if we’re not seeing clinically significant GVH. And that’s why I think that represents really the standard of care. 

You know, sort of, if you want to comment on sort of recent developments, you know, I think what’s in this space right now that’s, you know, being investigated further is, as I mentioned, the addition of a JAK inhibitor, ruxolitinib to CNI-based prophylaxis. So we know just giving tacrolimus and methotrexate is not a relatively toxic treatment regimen for GVH prophylaxis. It lacks efficacy, you know, in terms of preventing clinically significant graft-versus-host disease, but there has been a phase two study, you know, performed or led by MGH that demonstrated sort of the addition of ruxolitinib really attenuates severe acute and chronic graft-versus-host disease. So that’s something that’s under investigation and being compared against post-transplant cyclophosphamide. There have been also sort of graft manipulation studies, primarily led by ORCA, that look at sort of separating out populations of T-cells that may impact graft-versus-host disease. And these studies are demonstrating potentially an attenuation of toxicity with that approach and potentially, compared to post-transplant cyclophosphamide attenuated toxicity as well, with comparable sort of GVH outcomes.

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