Chimeric antigen receptor T‐cell therapy combined with autologous stem cell transplantation improved progression‐free survival of relapsed or refractory diffuse large B‐cell lymphoma patients: A single‐center, retrospective, cohort study

Abstract

Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67 R/R DLBCL patients were included, among which 21 patients underwent ASCT-CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT-CART and ASCT groups was 4.71 � 10 8 /kg and 5.36 � 10 8 /kg, respectively (p = 0.469). The median number of CD34 + cell numbers that were infused in the ASCT-CART and ASCT groups was 2.41 � 10 6 /kg and 3.05 � 10 6 /kg, respectively (p = 0.663). The median number of CART cells that were infused was 2.63 � 10 6 /kg with a median transduction rate of 59.83%. The objective response rates to ASCT-CART and ASCT therapy were 90% and 89%, respectively (p = 1.000). However, the ASCT-CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p = 0.003). The ASCT-CART group demonstrated superior 3 year progression-free survival (PFS) (80% vs. 44%; p = 0.036) and lower 3 year relapse/progression rate (15% vs. 56%; p = 0.015) compared to the ASCT group. However, the 3 year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p = 0.545). For R/R DLBCL patients, ASCT-CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT-CART therapy can be used as a salvage therapy for R/R DLBCL patients.Tao Wang and Lili Xu are contributed equally to the manuscript.

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies

“…A recent study has demonstrated that auto-HSCT in combination with CAR-T cell therapy achieved higher ORR, PFS, and OS compared with CAR-T cell therapy alone, indicating that bridging auto-HSCT is able to promote durable and deep remission (115). Another clinical trial has compared the efficacy of the combination of auto-HSCT and CAR-T cell therapy with auto-HSCT alone, and it showed that the combination group had higher CR rate and 3-year PFS than the auto-HSCT group, with lower 3 year relapse rate (116). The above studies suggest that the combination of auto-HSCT and CAR-T cell therapy could exert a synergistic effect in remission induction (114,(116)(117)(118).…”

“…Another clinical trial has compared the efficacy of the combination of auto-HSCT and CAR-T cell therapy with auto-HSCT alone, and it showed that the combination group had higher CR rate and 3-year PFS than the auto-HSCT group, with lower 3 year relapse rate (116). The above studies suggest that the combination of auto-HSCT and CAR-T cell therapy could exert a synergistic effect in remission induction (114,(116)(117)(118). In addition, localized radiotherapy and cryoablation are effective bridging therapies for R/R MM patients with bulky mass.…”

Double systemic cytokine release syndrome following sequential infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T cells after autologous hematopoietic stem cell transplantation for a central diffuse large B-cell lymphoma patient: A case report and literature review

“…It has been reported in the literature that CRS was observed in 37% to 93% of patients with hematologic malignancies treated with autologous CD19-CAR T cells ( 6 – 8 ). Wang T analyzed the safety of 21 patients with DLBCL treated with ASCT-CART, and the results showed that 71% of patients developed grade 1-2 CRS and 5% of patients suffered from grade 3-4 CRS ( 9 ). The incidence and degree of CRS depend on tumor type, tumor burden, CAR-T cell dose, co-stimulatory domain type, CAR T cell activation, and expansion ( 10 ).…”

Combination strategies to optimize the efficacy of chimeric antigen receptor T cell therapy in haematological malignancies

“…Wei et al compared CAR T cell infusion after ASCT and CAR T cells alone and demonstrated that the best ORR, CR rate and long-term outcomes improved significantly in the combination group (62). In another study comparing CAR T cell infusion after ASCT and ASCT alone, the combination group showed higher CR rate (71% vs. 33%; p=0.003) and 3year PFS (80% vs. 44%; p=0.036) than the ASCT group, and demonstrated lower 3 year relapse/progression rate (15% vs. 56%; p=0.015) (63). Incidences of adverse events differ from studies and were manageable in most cases (Table 2).…”