TY - JOUR
T1 - Immune checkpoint inhibitors as a bridge to allogeneic transplantation with posttransplant cyclophosphamide
AU - Schoch, Laura K.
AU - Cooke, Kenneth R.
AU - Wagner-Johnston, Nina D.
AU - Gojo, Ivana
AU - Swinnen, Lode J.
AU - Imus, Philip
AU - Fuchs, Ephraim J.
AU - Levis, Mark
AU - Ambinder, Richard F.
AU - Jones, Richard J.
AU - Gladstone, Douglas E.
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/9/11
Y1 - 2018/9/11
N2 - Published reports suggest thatimmunecheckpoint inhibitors (ICIs) before allogeneic blood or marrow transplantation (alloBMT) may increase the incidence of graft-versus-host disease (GvHD), immune-related adverse events, and nonrelapse mortality (NRM); this led to the US Food and Drug Administration issuing a "Warning and Precaution" regarding the potential for life-threatening immune-mediated complications associated with alloBMT after nivolumab and pembrolizumab. We retrospectively reviewed the outcomes of 14 consecutive patients who received ICIs as their final salvage therapy before T-cell-replete alloBMT using reduced-intensity conditioning. All patients received posttransplant cyclophosphamide (PTCy), which significantly limits severe GvHD, even in the mismatched-donor setting. There was no grade 3-4 acute GvHD (aGvHD), and all 6 cases of grade 2 aGvHD readily resolved with immunosuppression. No patient experienced veno-occlusive disease of the liver, other immune-related adverse events, chronic GvHD, or NRM. There have been 2 relapses (15-month median follow-up), with 12 of 14 patients remaining alive, well, and progression-free. The only death was a result of disease relapse. Although more experience is needed, our data suggest that concerns over immunologic complications associated with ICIs should not preclude allogeneic bone marrow transplantation with PTCy as GvHD prophylaxis.
AB - Published reports suggest thatimmunecheckpoint inhibitors (ICIs) before allogeneic blood or marrow transplantation (alloBMT) may increase the incidence of graft-versus-host disease (GvHD), immune-related adverse events, and nonrelapse mortality (NRM); this led to the US Food and Drug Administration issuing a "Warning and Precaution" regarding the potential for life-threatening immune-mediated complications associated with alloBMT after nivolumab and pembrolizumab. We retrospectively reviewed the outcomes of 14 consecutive patients who received ICIs as their final salvage therapy before T-cell-replete alloBMT using reduced-intensity conditioning. All patients received posttransplant cyclophosphamide (PTCy), which significantly limits severe GvHD, even in the mismatched-donor setting. There was no grade 3-4 acute GvHD (aGvHD), and all 6 cases of grade 2 aGvHD readily resolved with immunosuppression. No patient experienced veno-occlusive disease of the liver, other immune-related adverse events, chronic GvHD, or NRM. There have been 2 relapses (15-month median follow-up), with 12 of 14 patients remaining alive, well, and progression-free. The only death was a result of disease relapse. Although more experience is needed, our data suggest that concerns over immunologic complications associated with ICIs should not preclude allogeneic bone marrow transplantation with PTCy as GvHD prophylaxis.
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U2 - 10.1182/pbloodadvances.2018019208
DO - 10.1182/pbloodadvances.2018019208
M3 - Article
C2 - 30190282
AN - SCOPUS:85057726438
SN - 2473-9529
VL - 2
SP - 2226
EP - 2229
JO - Blood advances
JF - Blood advances
IS - 17
ER -