Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant

Abstract

BackgroundChimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival.MethodsA single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy.ResultsThe median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021).ConclusionsOur study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.

Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis

“…A common and challenging side effect associated with CAR T-cell therapy is ICANS, which occurs in 20–60% of patients [ 46 ], of whom 12–30% showed severe (≥grade 3) symptoms. Similar to RR and CRS, a lower event rate in ICANS revealed a better treatment outcome.…”

“…A recent investigation conducted by Cao et al. aimed to assess the efficacy of employing a second allo-HSCT following CAR T-cell therapy in patients with r/r B-ALL [ 46 ]. Their findings revealed that integrating CAR-T therapy with a subsequent consolidation allo-HSCT significantly enhanced the observed outcomes, with MRD-CR of 90.5% and RR of 10.5% in individuals with r/r B-ALL and post-transplant relapse.…”

G-CSF-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for CAR Therapy

“…The paradigmatic case of this potential use would be multiple myeloma or NHL, where many patients undergo CAR-T therapy after relapse following autologous transplantation [62]. In the case of LAL, successful cases have been described with the infusion of allogeneic CAR-T cells from the donor after early relapse following allogeneic HSCT [63][64][65]. On the other hand, the hematopoietic toxicities of autologous CAR-T cell therapies are a major concern, and there are many cases reported that have required the infusion of hematopoietic progenitors as rescue [66,67].…”

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy

“…The paradigmatic case of this potential use would be multiple myeloma or NHL, where many patients undergo CAR-T therapy after relapse following autologous transplantation [ 70 ]. In the case of LAL, successful cases have been described with the infusion of allogeneic CAR-T cells from the donor after early relapse following allogeneic HSCT [ 71 , 72 , 73 ]. In addition to this, this mobilized product could be used to treat the hematopoietic toxicities of autologous CAR-T-cell therapies, which are a major concern, and there are many cases reported that have required the infusion of hematopoietic progenitors as rescue [ 74 , 75 ].…”