The panel discusses the iNTERGRATE trial of ibrutinib in combination with prednisone as frontline therapy for chronic GVHD.
Yi-Bin Chen, MD:To the credit of investigators and the company, there was an effort to try and move ibrutinib [Imbruvica] to the frontline setting in this study that was recently published. Catherine, do you want to take us through this?
Catherine J. Lee, MD, MS: This was another attempt to see whether ibrutinib or a novel agent would be superior to standard of care prednisone for upfront treatment of moderate-to-severe chronic GVHD [graft-versus-host disease]. This was a phase 3 randomized blinded trial called the iNTEGRATE trial [NCT02959944]. It was a global trial where ibrutinib and prednisone was compared to placebo and prednisone. So there were about 193 enrolled patients aged 12 or higher. And the primary end point was overall response rate at 48 weeks. And then there were a number of secondary end points including survival, duration of response, time to withdrawal of immunosuppression, of course, early chronic GVHD symptom scale, and safety or toxicity. And unfortunately, the primary outcome wasn’t met. There was no statistically significant differences in the 48-week overall response rate nor were there any significant differences in any of the secondary end points, as you can see here. There might have been a trend to more rapid withdrawal of steroids in the ibrutinib arm but that was the main conclusion of the study. So, this represents, I think, the 8th randomized trial for upfront treatment of chronic GVHD which did not result in a benefit. The other ones, which some of them are CTN [Clinical Trials Network] trials, either did not result in benefit or were closed [due] to toxicity. So far we still do not have a novel agent that has been found to be better than steroids.
Yi-Bin Chen, MD:So that’s pretty sobering for us in the field here trying to improve upon care. I think it highlights what our discussion was before about being able to find a system to select for the higher risk patients in some way, be it at diagnosis before, or even after, to be able to do trials to pick the patients who will definitely be able to have the most benefit. I will get to the question now, and saying from reading the iNTEGRATE trial, did it change anything for you guys in terms of practice at all? Certainly not for us at Mass General [Hospital], I’d say.
Corey S. Cutler, MD, MPH, FRCPC: Not for us either, and we didn’t use it in the frontline. I think there were some interesting signals from the trial. I think it actually does confirm that ibrutinib does have clinical activity because of the nice trends in prolonging response times and a slightly higher trend towards discontinuation of both steroids and other immunosuppressants. I think it does confirm that this is an active agent in chronic graft-versus-host disease, but it’s probably going to remain in the second line or beyond.
Yi-Bin Chen, MD:No. I agree.
Transcript edited for clarity.