Contributions
Abstract: EP1294
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
More than 90% complete remission (CR) can be achieved in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) with chimeric antigen receptor T cell (CART) therapy. However, a small portion of patients still cannot obtain CR or minimal residual disease (MRD) negative by CART therapy. Programmed cell death protein 1 (PD-1) inhibitor can enhance anti-leukemia effect of CART cells, but increased early immune toxicity has been reported in allogeneic hematopoietic stem cell transplantation (allo-HSCT) after PD-1blockade in lymphoma patients.
Aims
In present study, the influence of prior application of PD-1inhibitor on acute graft-versus-host disease (aGVHD) after allo-HSCT for r/r B-ALL patients who achieved CR with CART was investigated.
Methods
Five pediatric r/r B-ALL patients who achieved CR by CART combined with PD-1 inhibitor and then underwent allo-HSCT were analyzed retrospectively. The median age was 4 (3-9) years old. Three cases were with normal cytogenetics and molecular genetics, and 2 cases were with both complex karyotypes and E2A/PBX1 (one of them also with TP53 mutation). Before allo-HSCT, all patients achieved CR (MRD- in 3, MRD+ in 2) by CART combined with PD-1 inhibitor. CD19-CART and/CD22-CART were used. Toripalimab at 3mg/kg was applied for one (n=4) or two (n=1) doses if CR or MRD- was not achieved two weeks after CART therapy. All patients underwent allo-HSCT from haploidentical donors with myeloablative conditioning regimens (TBI/fludarabine/ATG in 2, busulfan/fludarabine/ATG in 3). Cyclosporine, MMF and short-term MTX were employed for GVHD prophylaxis. Interval between last PD-1 treatment and HSCT was 45 (14-60) days.
Results
All patients achieved durable engraftment. Two patients developed hyper-acute GVHD with a noninfectious febrile syndrome and severe liver dysfunction and resolved with multiple immunosuppressants including methylprednisolone (up to 4mg/kg), cyclosporine, MMF, basiliximab, ruxolitinib, and MTX. Much higher incidences of overall aGVHD and severe aGVHD were noted in this cohort compared with our previous study that r/r B-ALL patients achieved CR with CART then bridge to allo-HSCT without prior PD-1 treatment (Zhang Y, et al. Br J of Haematol. 2020;189:146-52). Two cases had chronic GVHD. No severe hemorrhagic cystitis and other infections were found. Three patients relapsed at 3, 5, 6 months and died from relapse at 10, 12, 12 months after HSCT. One patient died from severe aGVHD and transplant-associated thrombotic microangiopathy (TA-TMA) at 4 months post-transplant. One patient has been surviving free of disease.
Conclusion
Our preliminary clinical results has shown that PD-1 inhibitor significantly increases the incidence and severity of aGVHD after allo-HSCT in pediatric r/r B-ALL patients who obtained CR with CART. Severe hyper-acute GVHD has been seen that needs to use multiply immunosuppressants timely to prevent from multi-organ failure via cytokine storm. It suggests that PD-1 inhibitor should be avoided as possible if allo-HSCT is scheduled later.
Keyword(s): Allogeneic hematopoietic stem cell transplant, CAR-T, Graft-versus-host disease (GVHD)
Abstract: EP1294
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
More than 90% complete remission (CR) can be achieved in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) with chimeric antigen receptor T cell (CART) therapy. However, a small portion of patients still cannot obtain CR or minimal residual disease (MRD) negative by CART therapy. Programmed cell death protein 1 (PD-1) inhibitor can enhance anti-leukemia effect of CART cells, but increased early immune toxicity has been reported in allogeneic hematopoietic stem cell transplantation (allo-HSCT) after PD-1blockade in lymphoma patients.
Aims
In present study, the influence of prior application of PD-1inhibitor on acute graft-versus-host disease (aGVHD) after allo-HSCT for r/r B-ALL patients who achieved CR with CART was investigated.
Methods
Five pediatric r/r B-ALL patients who achieved CR by CART combined with PD-1 inhibitor and then underwent allo-HSCT were analyzed retrospectively. The median age was 4 (3-9) years old. Three cases were with normal cytogenetics and molecular genetics, and 2 cases were with both complex karyotypes and E2A/PBX1 (one of them also with TP53 mutation). Before allo-HSCT, all patients achieved CR (MRD- in 3, MRD+ in 2) by CART combined with PD-1 inhibitor. CD19-CART and/CD22-CART were used. Toripalimab at 3mg/kg was applied for one (n=4) or two (n=1) doses if CR or MRD- was not achieved two weeks after CART therapy. All patients underwent allo-HSCT from haploidentical donors with myeloablative conditioning regimens (TBI/fludarabine/ATG in 2, busulfan/fludarabine/ATG in 3). Cyclosporine, MMF and short-term MTX were employed for GVHD prophylaxis. Interval between last PD-1 treatment and HSCT was 45 (14-60) days.
Results
All patients achieved durable engraftment. Two patients developed hyper-acute GVHD with a noninfectious febrile syndrome and severe liver dysfunction and resolved with multiple immunosuppressants including methylprednisolone (up to 4mg/kg), cyclosporine, MMF, basiliximab, ruxolitinib, and MTX. Much higher incidences of overall aGVHD and severe aGVHD were noted in this cohort compared with our previous study that r/r B-ALL patients achieved CR with CART then bridge to allo-HSCT without prior PD-1 treatment (Zhang Y, et al. Br J of Haematol. 2020;189:146-52). Two cases had chronic GVHD. No severe hemorrhagic cystitis and other infections were found. Three patients relapsed at 3, 5, 6 months and died from relapse at 10, 12, 12 months after HSCT. One patient died from severe aGVHD and transplant-associated thrombotic microangiopathy (TA-TMA) at 4 months post-transplant. One patient has been surviving free of disease.
Conclusion
Our preliminary clinical results has shown that PD-1 inhibitor significantly increases the incidence and severity of aGVHD after allo-HSCT in pediatric r/r B-ALL patients who obtained CR with CART. Severe hyper-acute GVHD has been seen that needs to use multiply immunosuppressants timely to prevent from multi-organ failure via cytokine storm. It suggests that PD-1 inhibitor should be avoided as possible if allo-HSCT is scheduled later.
Keyword(s): Allogeneic hematopoietic stem cell transplant, CAR-T, Graft-versus-host disease (GVHD)