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Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting
Pfeiffer, T., Tzannou, I., Wu, M., Ramos, C., Sasa, G., Martinez, C., Lulla, P., Krance, R. A., Scherer, L., Ruderfer, D., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;:Of1-of7
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Editor's Choice
Abstract
PURPOSE Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus. PATIENTS AND METHODS We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either unresponsive to or patients were unable to tolerate standard antiviral therapies. Fifty-eight adult and pediatric patients were enrolled and treated. RESULTS Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion. CONCLUSIONS In this open-label trial, treatment of refractory viral infections/disease in allo-HCT recipients with posoleucel was feasible, safe, and effective.
PICO Summary
Population
Adult and pediatric allogeneic HSCT recipients infected with one or more of adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus (n=58)
Intervention
Single intravenous infusion of 2 × 107/m2 of posoleucel with the option to receive a second infusion after four weeks and additional infusions at biweekly intervals thereafter.
Comparison
None
Outcome
Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion.
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Practice preferences for consolidative HSCT following tisagenlecleucel in children and young adults with B-ALL
McNerney, K. O., Moskop, A., Winestone, L. E., Baggott, C., Talano, J. A., Schiff, D., Rossoff, J., Modi, A., Verneris, M. R., Laetsch, T. W., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Tisagenlecleucel achieves excellent complete remission rates in children and young adults with relapsed or refractory B-acute lymphoblastic leukemia (B-ALL), but approximately 50% maintain long-term remissions. Consolidative hematopoietic stem cell transplant (cHSCT) is a potential strategy to reduce relapse risk but carries substantial short- and long-term toxicities. Additionally, several strategies for management of B-cell recovery (BCR) and next-generation sequencing (NGS) positivity post-tisagenlecleucel exist without an accepted standard. We hypothesized that practice preferences surrounding cHSCT as well as management of BCR and NGS positivity varies across tisagenlecleucel-prescribing physicians and sought to characterize current practice preferences. METHODS A survey focused on preferences regarding the use of cHSCT, management of BCR, and NGS positivity was distributed to physicians that prescribe tisagenlecleucel for children and young adults with B-ALL. Responses were collected from August 2022 to April 2023. RESULTS Fifty-nine unique responses were collected across 43 institutions. All respondents prescribed tisagenlecleucel for children and young adults. The clinical focus of respondents was HSCT in 71% followed by leukemia/lymphoma in 24%. In HSCT-naïve patients receiving tisagenlecleucel, 57% of respondents indicated they made individualized decision for cHSCT based on patient factors, while 22% indicated they would avoid and 21% indicated they would pursue cHSCT where feasible. Select factors influenced >50% of respondents towards recommending cHSCT (either increased likelihood or would always recommend) including pre-infusion disease burden >25%, primary refractory B-ALL, M3 bone marrow following re-induction for relapse, KMT2A-rearranged B-ALL, history of blinatumomab non-response, and HSCT naïve status. Most respondents indicated they would pursue HSCT for HSCT-naïve, total body irradiation candidates with BCR before 6 months post-tisagenlecleucel or with NGS positivity at 1 or 3 months post-tisagenlecleucel, although there was variability about whether to proceed to HSCT directly or give intervening therapy prior to HSCT. The proportion of respondents recommending HSCT for BCR or NGS positivity decreased in those with a history of HSCT, non-TBI-candidates, or trisomy 21. CONCLUSIONS The results of this survey indicate there exists significant practice variability regarding the use of cHSCT as well as interventions for post-tisagenlecleucel BCR or NGS positivity. These results highlight areas for which ongoing clinical trials could inform more standardized practice.
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Factors Impacting Overall and Event-Free Survival following Post-Chimeric Antigen Receptor T Cell Consolidative Hematopoietic Stem Cell Transplantation
Molina, J. C., Steinberg, S. M., Yates, B., Lee, D. W., Little, L., Mackall, C. L., Shalabi, H., Shah, N. N.
Transplantation and cellular therapy. 2022;28(1):31.e1-31.e9
Abstract
Hematopoietic stem cell transplantation (HSCT) may be used to consolidate chimeric antigen receptor (CAR) T cell therapy-induced remissions for patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL), but little is known about the factors impacting overall survival (OS) and event-free survival (EFS) for post-CAR hematopoietic stem cell transplantation (HSCT). The present study's primary objective was to identify factors associated with OS and EFS for consolidative HSCT following CAR-induced complete remission (CR) in transplantation-naïve patients. Secondary objectives included evaluation of OS/EFS, relapse-free survival and cumulative incidence of relapse for all patients who proceeded to HSCT, stratified by first and second HSCT, as well as the tolerability of HSCT following CAR-induced remission. This was a retrospective review of children and young adults enrolled on 1 of 3 CAR T cell trials at the National Cancer Institute targeting CD19, CD22, and CD19/22 (ClinicalTrials.gov identifiers NCT01593696, NCT02315612, and NCT03448393) who proceeded directly to HSCT following CAR T cell therapy. Between July 2012 and February 2021, 46 children and young adults with pre-B ALL went directly to HSCT following CAR therapy. Of these patients, 34 (74%) proceeded to a first HSCT, with a median follow-up of 50.8 months. Transplantation-naïve patients were heavily pretreated prior to CAR T cell therapy (median, 3.5 lines of therapy; range, 1 to 12) with significant prior immunotherapy exposure (blinatumomab, inotuzumab, and/or CAR T cell therapy in patients receiving CD22 or CD19/22 constructs (88%; 15 of /17)). Twelve patients (35%) had primary refractory disease, and the median time from CAR T cell infusion to HSCT Day 0 was 54.5 days (range, 42 to 127 days). The median OS following first HSCT was 72.2 months (95% confidence interval [CI], 16.9 months to not estimable [NE]), with a median EFS of 36.9 months (95% CI, 5.2 months to NE). At 12 and 24 months, the OS was 76.0% (95% CI, 57.6% to 87.2%) and 60.7% (95% CI, 40.8% to 75.8%), respectively, and EFS was 64.6% (95% CI, 46.1% to 78.1%) and 50.9% (95% CI, 32.6% to 66.6%), respectively. The individual factors associated with both decreased OS and EFS in univariate analyses for post-CAR consolidative HSCT in transplantation-naïve patients included ≥5 prior lines of therapy (not reached [NR] versus 12.4 months, P = .014; NR versus 4.8 months, P = .063), prior blinatumomab therapy (NR versus 16.9 months, P = .0038; NR versus 4.4 months, P = .0025), prior inotuzumab therapy (NR versus 11.5 months, P = .044; 36.9 months versus 2.7 months, P = .0054) and ≥5% blasts (M2/M3 marrow) pre-CAR T cell therapy (NR versus 17 months, P = .019; NR versus 12.2 months, P = .035). Primary refractory disease was associated with improved OS/EFS post-HSCT (NR versus 21.9 months, P = .075; NR versus 12.2 months, P = .024). Extensive prior therapy, particularly immunotherapy, and high disease burden each individually adversely impacted OS/EFS following post-CAR T cell consolidative HSCT in transplantation-naïve patients, owing primarily to relapse. Despite this, HSCT remains an important treatment modality in long-term cure. Earlier implementation of HSCT before multiply relapsed disease and incorporation of post-HSCT risk mitigation strategies in patients identified to be at high-risk of post-HSCT relapse may improve outcomes.
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Comparisons of Long-Term Survival and Safety of Haploidentical Hematopoietic Stem Cell Transplantation After CAR-T Cell Therapy or Chemotherapy in Pediatric Patients With First Relapse of B-Cell Acute Lymphoblastic Leukemia Based on MRD-Guided Treatment
Hu, G., Cheng, Y., Zuo, Y., Chang, Y., Suo, P., Jia, Y., Lu, A., Wang, Y., Jiao, S., Zhang, L., et al
Frontiers in immunology. 2022;13:915590
Abstract
Measurable residual disease (MRD) positivity before haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an independent prognostic factor in determining outcomes in patients with B-cell acute lymphoblastic leukemia (ALL). In this study, we conducted a parallel comparison of the efficacy and safety in patients with suboptimal MRD response after reinduction who underwent haplo-HSCT after chimeric antigen receptor T-cell (CAR-T) therapy or chemotherapy. Forty B-cell ALL patients who relapsed after first-line chemotherapy and with an MRD ≥0.1% after reinduction were analyzed. The median pre-HSCT MRD in the CAR-T group (n = 26) was significantly lower than that in the chemotherapy group (n = 14) (0.009% vs. 0.3%, p = 0.006). The CAR-T group exhibited a trend toward improved 3-year leukemia-free survival and a significantly improved 3-year overall survival compared to the chemotherapy group [71.8% (95% confidence interval (CI): 53.9-89.6) vs. 44.4% (95% CI: 15.4-73.4), p = 0.19 and 84.6% (95% CI: 70.6-98.5) vs. 40.0% (95% CI: 12.7-67.2), p = 0.008; respectively]. Furthermore, no increased risk of graft-versus-host disease, treatment-related mortality, or infection was observed in the CAR-T group. Our study suggests that CAR-T therapy effectively eliminates pre-HSCT MRD, resulting in better survival in the context of haplo-HSCT.
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Three-year results from phase 1 of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia
Wayne, A. S., Huynh, V., Hijiya, N., Rouce, R. H., Brown, P. A., Krueger, J., Kitko, C. L., Ziga, E. D., Hermiston, M. L., Richards, M. K., et al
Haematologica. 2022
Abstract
The 3-year results are presented for ZUMA-4, a phase 1/2 multicenter study evaluating the safety and efficacy of KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pediatric/adolescent patients with relapsed/refractory (R/R) Bcell acute lymphoblastic leukemia (B-ALL). Phase 1 explored two dose levels and formulations. The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Of 31 enrolled patients, KTE-X19 was administered to 24 (median age 13.5 years, range 3-20; median follow-up 36.1 months). No DLTs were observed. All treated patients had grade ≥3 adverse events, commonly hypotension (50%) and anemia (42%). Grade 3 cytokine release syndrome rates were 33%, 75%, 27%, and 22% in the all-treated, 2×106, 1×106 (68 mL formulation), and 1×106 (40 mL formulation) CAR T cells/kg groups; 21%, 25%, 27%, and 11% of patients experienced grade ≥3 neurologic events, respectively. Overall complete remission (CR) rates (including CR with incomplete hematologic recovery) were 67%, 75%, 64%, and 67% in the all-treated, 2×106, 1×106 (68 mL), and 1×106 (40 mL) CAR T cells/kg groups, respectively. Overall minimal residual disease (MRD)-negativity rates were 100% among responders; 88% of responders underwent subsequent allogeneic stem-cell transplant (alloSCT). In the 1×106 (40 mL) group (recommended phase 2 dose), median duration of remission censored at alloSCT and median overall survival were not reached. Pediatric/adolescent patients with R/R B-ALL achieved high MRD-negative remission rates with manageable safety profile after a single dose of KTE-X19. Phase 2 is ongoing at the 1×106 CAR T cells/kg (40 mL) dose.
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Extracorporeal Membrane Oxygenation Candidacy in Pediatric Patients Treated With Hematopoietic Stem Cell Transplant and Chimeric Antigen Receptor T-Cell Therapy: An International Survey
Ghafoor, S., Fan, K., Di Nardo, M., Talleur, A. C., Saini, A., Potera, R. M., Lehmann, L., Annich, G., Wang, F., McArthur, J., et al
Frontiers in oncology. 2021;11:798236
Abstract
INTRODUCTION Pediatric patients who undergo hematopoietic cell transplant (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at high risk for complications leading to organ failure and the need for critical care resources. Extracorporeal membrane oxygenation (ECMO) is a supportive modality that is used for cardiac and respiratory failure refractory to conventional therapies. While the use of ECMO is increasing for patients who receive HCT, candidacy for these patients remains controversial. We therefore surveyed pediatric critical care and HCT providers across North America and Europe to evaluate current provider opinions and decision-making and institutional practices regarding ECMO use for patients treated with HCT or CAR-T. METHODS An electronic twenty-eight question survey was distributed to pediatric critical care and HCT providers practicing in North America (United States and Canada) and Europe through the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network and individual emails. Responses to the survey were recorded in a REDCap(®) database. RESULTS Two-hundred and ten participants completed the survey. Of these, 159 (76%) identified themselves as pediatric critical care physicians and 47 (22%) as pediatric HCT physicians or oncologists. The majority (99.5%) of survey respondents stated that they would consider patients treated with HCT or CAR-T therapy as candidates for ECMO support. However, pediatric critical care physicians identified more absolute and relative contraindications for ECMO than non-pediatric critical care physicians. While only 0.5% of respondents reported that they consider HCT as an absolute contraindication for ECMO, 6% of respondents stated that ECMO is contraindicated in HCT patients within their institution and only 23% have an institutional protocol or policy to guide the evaluation for ECMO candidacy of these patients. Almost half (49.1%) of respondents would accept a survival to hospital discharge of 20-30% for pediatric HCT patients requiring ECMO as adequate. CONCLUSIONS ECMO use for pediatric patients treated with HCT and CAR-T therapy is generally acceptable amongst physicians. However, there are differences in the evaluation and decision-making regarding ECMO candidacy amongst providers across medical specialties and institutions. Therefore, multidisciplinary collaboration is an essential component in establishing practice guidelines and advancing ECMO outcomes for these patients.
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Effect of anti-CD19 chimeric antigen receptor T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia and its prognosis
Li, N., Li, H.
Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2021;26(1):159-165
Abstract
PURPOSE To explore the efficacy of chimeric antigen receptor (CAR)-T cell therapy in children with relapsed or refractory acute B-lymphocytic leukemia (B-ALL) and the influencing factors for their prognosis. METHODS A retrospective analysis was performed on the clinical data of 46 children with relapsed or refractory B-ALL, who were admitted to and treated in our hospital from January 2015 to October 2017, and the remission and post-infusion adverse reactions were observed in all the patients. Besides, the survival of the patients was followed up and recorded, and the influencing factors for the prognosis were identified by univariate and multivariate Cox regression analyses. RESULTS Bone marrows were routinely monitored after infusion of CAR-T cells. It was found that 35 children patients achieved morphologic complete remission, had a lower level of minimal residual disease (MRD) than that before treatment and exhibited a response rate of 76.1%, of whom there were 33 cases of MRD-negative remission. Different degrees of cytokine release syndrome (CRS) occurred in 41 out of 46 children, consisting of 37 (80.4%) cases of grade I-II CRS and 4 (8.7%) cases of grade III-IV CRS. The concentrations of serum interleukin (IL)-6, interferon-? (IFN-?), ferritin and C-reactive protein (CRP) obviously rose during CRS, and their peak values in the patients with grade III-IV CRS were notably higher than those in grade I-II CRS patients (p<0.001). At the end of follow-up, the median follow-up time was 28.2 months, and the 3-year overall survival (OS) and event-free survival (EFS) rates were 28.3% and 13.0%, respectively. The results also showed that tumor burden =5% prior to CAR-T cell therapy [hazard ratio (HR) =3.496, 95% confidence interval (CI) =1.448-9.891, p=0.014] and non-combination with hematopoietic stem cell transplant (HSCT) therapy (HR =0.890, 95% CI =0.543-0.904, p=0.025) were independent risk factors for the prognosis of the patients. CONCLUSIONS Anti-cluster of classification (CD) 19 CAR-T cell therapy is safe and efficacious against relapsed or refractory B-ALL in children. Reducing the tumor burden before infusion of CAR-T cells and combined with HSCT after infusion are independent factors for improving the prognosis of the patients.
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Impact of High Disease Burden on Survival in Pediatric Patients with B-ALL Treated with Tisagenlecleucel
Ravich, J. W., Huang, S., Zhou, Y., Brown, P., Pui, C. H., Inaba, H., Cheng, C., Gottschalk, S., Triplett, B. M., Bonifant, C. L., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND CD19-specific chimeric antigen receptor (CAR) T-cell therapies, including the FDA-approved tisagenlecleucel, induce high rates of remission in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, post-treatment relapse remains an issue. Optimal management of B-ALL after tisagenlecleucel treatment remains elusive and continued tracking of outcomes is necessary to establish a standard of care for this population. OBJECTIVE We sought to evaluate outcomes on the real-world use of tisagenlecleucel in a contemporary pediatric patient population, and to identify risk factors influencing event-free survival (EFS) and overall survival (OS). Additionally, we aimed to describe post tisagenlecleucel management strategies, including use of allogeneic hematopoietic cell transplant (AlloHCT) and/or repeat CAR T-cell infusions. STUDY DESIGN We report on 31 pediatric and adolescent and young adult patients (AYA) with B-ALL, treated with lymphodepleting chemotherapy followed by tisagenlecleucel. Patients were treated at Johns Hopkins Hospital and St. Jude Children's Research Hospital between March 2018 and November 2020. Data on patient, disease and treatment characteristics were collected retrospectively from medical records and described. EFS and OS were estimated by the Kaplan-Meier method and compared by the log-rank test. Single-factor and multiple-factor analysis of EFS and OS were performed by fitting Cox regression models. RESULTS Of the 30 evaluable patients, 25 (83.3%) experienced a complete response, with 21 having negative minimal residual disease (MRD). Treatment was well tolerated, with expected rates of cytokine release syndrome (61.3%) and immune effector cell-associated neurotoxicity (29%). After initial CR, 12 patients (48%) had subsequent disease recurrence, with CD19-negative relapse (n=6) occurring sooner than CD19-positive relapse (P?=?0.0125). With a median follow-up time of 386 days (range: 11-1187 days), the EFS for the entire cohort (n?=?31) at 6- and 12-months post infusion was 47% (95% confidence interval [CI]: 28.4-63.4%) and 35.2% (CI, 18.4-52.5%), respectively. In multivariate analysis, high pretreatment leukemic burden (=5% bone marrow blasts) was an independent risk factor for inferior EFS (HR 5.98 [95% CI, 1.1-32.4], P=0.0380) and OS (HR 4.2 [95% CI, 1.33-13.39, P?=?0.0148). CONCLUSIONS Tisagenlecleucel induced high initial response rates in a contemporary cohort of pediatric and AYA patients with B-ALL. However, 48% of patients experienced subsequent disease relapse, including 6 with antigen-escape variants. This highlights a considerable limitation of single-agent autologous CD19-CAR T-cell therapy. Pretreatment leukemic disease burden of =5% blasts was significantly associated with worse outcomes in this study, including lower EFS and OS. Our findings suggest that reducing pre-infusion leukemic burden is a viable treatment strategy to improve outcomes of CAR T-cell therapy.
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Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/Recurrent Minimal Residual Disease in First Complete Remission
Hu, G. H., Cheng, Y. F., Zuo, Y. X., Chang, Y. J., Suo, P., Wu, J., Jia, Y. P., Lu, A. D., Li, Y. C., Wang, Y., et al
Frontiers in immunology. 2021;12:731435
Abstract
BACKGROUND The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear. METHODS We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission. RESULTS A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8-90.7%) vs. 68.7% (95% CI, 47.7-89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8-90.7%) vs. 28.6% (95% CI, 4.9-52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion. CONCLUSIONS Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.
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Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy
Hu, G. H., Zhao, X. Y., Zuo, Y. X., Chang, Y. J., Suo, P., Wu, J., Jia, Y. P., Lu, A. D., Li, Y. C., Wang, Y., et al
Leukemia. 2021
Abstract
Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P?=?0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.