Contributions
Abstract: EP505
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
The prognosis of refractory/relapsed aggressive B-cell non-Hodgkin lymphoma (r/r B-NHL) is extremely poor, especially for the patients who failed to autologous chimeric antigen receptor-T (CAR-T) cells.
Aims
For r/r B-NHL, a clinical trial using haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with conditioning including allogeneic bispecific CAR-T cells targeting both CD19 and CD22 from the same donor (allo-CD19/CD22 CAR-T) has been registered, and the safety and efficacy will be evaluated.
Methods
From September 2020 to January 2021, 7 patients with r/r B-NHL were enrolled. The median age was 43 (26-54) years old. The diagnosis included diffuse large B-cell lymphoma (DLBCL, n=6) and Burkitt lymphoma (n=1). Four cases were with TP53 mutations. All patients failed to multi-line therapies, including chemotherapy (n=7), autologous HSCT (n=1), autologous CAR-T (n=6), local irradiation (n=4) and anti-PD1 antibodies (n=2). The disease status before transplant was stable disease (SD) in 1 case, partial remission (PR) in 3 and progressive disease (PD) in 3. Before the trial, the expression of CD19 and/or CD22 antigen in tumor tissue of all patients was positive confirmed by pathology. Conditioning with busulfan, fludarabine-based regimen combined with allo-CD19/CD22 CAR-T was applied. Tacrolimus, mycophenolate mofetil, a short-term methotrexate and antithymocyte globulin were used for graft-versus-host disease (GVHD) prophylaxis. The kinetics and function of CAR-T cells was monitored by quantitative PCR and flow cytometry. The efficacy was evaluated by PET-CT at 60 days after CAR-T infusion.
Results
The median CAR-T cells infused were 3.6 (1.87-4.0)×106/kg. Cytokine release syndrome (CRS) occurred in all cases with 2 cases in grade I, 2 cases in grade II and 3 cases in grade III. No immune effector cell-associated neurotoxicity syndrome (ICANS) was noted. Three cases with grade III CRS were relieved with methylprednisolone. Granulocyte colony-stimulating factor–mobilized peripheral blood stem cells were infused 7 days after CAR-T with the median CD34+ cells 6 (3-8.19)×106/kg. The neutrophil engraftment was achieved in all cases on median days 16 (11-24) post-transplant. Platelets were engrafted in 4 cases on median days 19 (16-65). No acute GVHD (aGVHD) was seen. CMV viremia occurred in 3 cases. Three patients developed grade I BKV hemorrhagic cystitis. The highest proportion of CAR-T cells in vivo was 90.2 (0.096-502) % on median 7 (6-71) days after CAR-T cell infusion. CAR-T cells were detected persistently in vivo in 6/7 (85.7%) patients and the longest lasting time was 140 days post-transplant so far. B-cell aplasia was documented in all cases during the follow-up. With the median follow-up 62 (30-153) days, all patients survived. Four cases have been evaluated by PET-CT, one case with DLBCL achieved PR first and then progression, one case obtained PR, and two cases achieved complete remission. For the other 3 cases short than 60 days after CAR-T therapy, the tumor sizes have shrinked significantly measured by B ultrasound.
Conclusion
CRS is manageable and has no influence on hematopoiesis reconstitution. CAR-T cells still exist persistently post-transplant in majority of patients, which may contribute a long-term anti-lymphoma effect. With current protocol, no aGVHD was observed, viral reactivation was mild and encouraging disease control was found. Haplo-HSCT with conditioning including allo-CD19/CD22 CAR-T cells is a safe and effective strategy for r/r B-NHL. Long-term follow-up is needed.
Keyword(s): CAR-T, Haploidentical stem cell transplantation, Non-Hodgkin's lymphoma, Refractory
Abstract: EP505
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
The prognosis of refractory/relapsed aggressive B-cell non-Hodgkin lymphoma (r/r B-NHL) is extremely poor, especially for the patients who failed to autologous chimeric antigen receptor-T (CAR-T) cells.
Aims
For r/r B-NHL, a clinical trial using haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with conditioning including allogeneic bispecific CAR-T cells targeting both CD19 and CD22 from the same donor (allo-CD19/CD22 CAR-T) has been registered, and the safety and efficacy will be evaluated.
Methods
From September 2020 to January 2021, 7 patients with r/r B-NHL were enrolled. The median age was 43 (26-54) years old. The diagnosis included diffuse large B-cell lymphoma (DLBCL, n=6) and Burkitt lymphoma (n=1). Four cases were with TP53 mutations. All patients failed to multi-line therapies, including chemotherapy (n=7), autologous HSCT (n=1), autologous CAR-T (n=6), local irradiation (n=4) and anti-PD1 antibodies (n=2). The disease status before transplant was stable disease (SD) in 1 case, partial remission (PR) in 3 and progressive disease (PD) in 3. Before the trial, the expression of CD19 and/or CD22 antigen in tumor tissue of all patients was positive confirmed by pathology. Conditioning with busulfan, fludarabine-based regimen combined with allo-CD19/CD22 CAR-T was applied. Tacrolimus, mycophenolate mofetil, a short-term methotrexate and antithymocyte globulin were used for graft-versus-host disease (GVHD) prophylaxis. The kinetics and function of CAR-T cells was monitored by quantitative PCR and flow cytometry. The efficacy was evaluated by PET-CT at 60 days after CAR-T infusion.
Results
The median CAR-T cells infused were 3.6 (1.87-4.0)×106/kg. Cytokine release syndrome (CRS) occurred in all cases with 2 cases in grade I, 2 cases in grade II and 3 cases in grade III. No immune effector cell-associated neurotoxicity syndrome (ICANS) was noted. Three cases with grade III CRS were relieved with methylprednisolone. Granulocyte colony-stimulating factor–mobilized peripheral blood stem cells were infused 7 days after CAR-T with the median CD34+ cells 6 (3-8.19)×106/kg. The neutrophil engraftment was achieved in all cases on median days 16 (11-24) post-transplant. Platelets were engrafted in 4 cases on median days 19 (16-65). No acute GVHD (aGVHD) was seen. CMV viremia occurred in 3 cases. Three patients developed grade I BKV hemorrhagic cystitis. The highest proportion of CAR-T cells in vivo was 90.2 (0.096-502) % on median 7 (6-71) days after CAR-T cell infusion. CAR-T cells were detected persistently in vivo in 6/7 (85.7%) patients and the longest lasting time was 140 days post-transplant so far. B-cell aplasia was documented in all cases during the follow-up. With the median follow-up 62 (30-153) days, all patients survived. Four cases have been evaluated by PET-CT, one case with DLBCL achieved PR first and then progression, one case obtained PR, and two cases achieved complete remission. For the other 3 cases short than 60 days after CAR-T therapy, the tumor sizes have shrinked significantly measured by B ultrasound.
Conclusion
CRS is manageable and has no influence on hematopoiesis reconstitution. CAR-T cells still exist persistently post-transplant in majority of patients, which may contribute a long-term anti-lymphoma effect. With current protocol, no aGVHD was observed, viral reactivation was mild and encouraging disease control was found. Haplo-HSCT with conditioning including allo-CD19/CD22 CAR-T cells is a safe and effective strategy for r/r B-NHL. Long-term follow-up is needed.
Keyword(s): CAR-T, Haploidentical stem cell transplantation, Non-Hodgkin's lymphoma, Refractory