Evaluation of infliximab as second-line treatment of acute graft versus host disease -validating response on day 7 and 28 as predictors of survival

TY - JOUR

T1 - Evaluation of infliximab as second-line treatment of acute graft versus host disease -validating response on day 7 and 28 as predictors of survival

AU - Nygaard, Marietta

AU - Andersen, Niels Smedegaard

AU - Moser, Claus Ernst

AU - Olesen, Gitte

AU - Schjødt, Ida Marie

AU - Heilmann, Carsten

AU - Sengeløv, Henrik

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Several immunosuppressive drugs have been proposed for second-line treatment of steroid-refractory acute graft versus host disease (aGvHD) after allogeneic hematopoietic stem cell transplantation. However, the studies on these drugs are small, retrospective, uncontrolled and use different endpoints. Therefore, it remains unknown which treatment is superior. We retrospectively evaluated 68 consecutive patients treated with infliximab for aGvHD. We adhered to recently proposed guidelines for aGvHD trials and thus evaluated response on day 7 and 28. Furthermore, we assessed the composite endpoint 6 months freedom from treatment failure (6MFTF). The majority of patients had grade III-IV aGvHD. We found that 41 patients (60%) responded on day 7 and 31 patients (46%) on day 28. Twenty-four patients (35%) achieved 6MFTF. The main reasons for failure within 6 months were death (n = 31) or additional immunosuppression (n = 16). By six and 24 months, 44 and 34% of the patients were alive respectively. Patients with response to infliximab on day 7 and 28 had significantly higher overall survival (OS) probability than non-responders. We show that response on day 7 and 28 identifies high and low risk groups. Patients who fail to respond should be identified early and offered alternative therapy.

AB - Several immunosuppressive drugs have been proposed for second-line treatment of steroid-refractory acute graft versus host disease (aGvHD) after allogeneic hematopoietic stem cell transplantation. However, the studies on these drugs are small, retrospective, uncontrolled and use different endpoints. Therefore, it remains unknown which treatment is superior. We retrospectively evaluated 68 consecutive patients treated with infliximab for aGvHD. We adhered to recently proposed guidelines for aGvHD trials and thus evaluated response on day 7 and 28. Furthermore, we assessed the composite endpoint 6 months freedom from treatment failure (6MFTF). The majority of patients had grade III-IV aGvHD. We found that 41 patients (60%) responded on day 7 and 31 patients (46%) on day 28. Twenty-four patients (35%) achieved 6MFTF. The main reasons for failure within 6 months were death (n = 31) or additional immunosuppression (n = 16). By six and 24 months, 44 and 34% of the patients were alive respectively. Patients with response to infliximab on day 7 and 28 had significantly higher overall survival (OS) probability than non-responders. We show that response on day 7 and 28 identifies high and low risk groups. Patients who fail to respond should be identified early and offered alternative therapy.

U2 - 10.1038/s41409-018-0099-3

DO - 10.1038/s41409-018-0099-3

M3 - Journal article

C2 - 29391524

SN - 0268-3369

VL - 53

SP - 844

EP - 851

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 7

ER -