Allison Barz Leahy
· Assistant Professor of Pediatrics (Oncology) at the Children's Hospital of PhiladelphiaVerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 2001–2026
About
Allison Barz Leahy, MD MSCE, is an Assistant Professor of Pediatrics (Oncology) at the Children's Hospital of Philadelphia. She is an attending physician in the Division of Oncology at the same hospital and serves as core faculty for Clinical Futures. Dr. Leahy is also a member of the Innovation Faculty at the Penn Center for Cancer Care Innovation, University of Pennsylvania, and is the Abramson Cancer Center (ACC) Cancer Research Training and Education (CRTEC) Representative for Penn Medicine. Her clinical expertise includes patient-reported outcomes, relapsed and refractory leukemia, and CAR T-cell therapies. Her research focuses on pediatric health outcomes, phase 1 clinical trials, and pediatric oncology, with particular emphasis on the development and assessment of novel immunotherapies and their associated outcomes. Dr. Leahy has contributed to numerous studies and publications in these areas, advancing understanding of treatment-related neurotoxicity, outpatient care delivery, and the financial aspects of pediatric CAR T-cell therapy.
Research signals
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Research topics
- Internal medicine
- Medicine
- Immunology
- Biology
- Bioinformatics
- Oncology
Selected publications
HemaSphere · 2026-04-01
articleOpen accessNeurotoxicity is a common and potentially life-threatening complication after chimeric antigen receptor T-cell therapy (CART) for pediatric B-cell acute lymphoblastic leukemia (B-ALL). The only consistently demonstrated clinical risk factor for severe neurotoxicity in prior studies is high, preinfusion bone marrow disease burden (DB). To better prognosticate this syndrome, we sought to identify preinfusion clinical, laboratory, and imaging risk factors for the development of severe neurotoxicity, stratified by DB. We determined the incidence of severe neurotoxicity (defined as Grade ≥3 neurologic event[s]) in children and young adults treated with investigational anti-CD19 or anti-CD22 CART products across eight clinical trials or with commercial tisagenlecleucel. We comprehensively examined the association of putative clinical, laboratory, and imaging factors with the development of severe neurotoxicity. The occurrence of a seizure was included as a secondary outcome. Severe neurotoxicity was observed in 45/442 (10%) patients and was more frequent in the high DB (26/107, 24%) than the low DB (17/312, 5%) cohort. In the high DB cohort, history of a prior transient neurologic insult was associated with severe neurotoxicity (adjusted odds ratio, 5.73; 95% CI, 1.63, 21.7; P = 0.007). In the low DB cohort, no studied risk factors were robustly associated with severe neurotoxicity. Risk factors associated were different in the high and low DB cohorts. Patients with high DB and a previous history of transient neurologic events had a higher risk of severe neurotoxicity. Although the frequency of severe neurotoxicity was much lower in low DB patients, low DB patients accounted for 40% of severe neurotoxicity cases. Future studies should consider patients with high or low DB separately.
Pediatric Blood & Cancer · 2026-04-10
articleOpen accessBlinatumomab has been shown to be highly effective for patients with pediatric B-ALL and has recently become standard of care therapy. Due to its past use in the clinical trial setting, there is limited information available about real-world administration. In this brief report, we describe our institutional experience administering blinatumomab during the first year as standard of care therapy, including initial challenges in providing access to patients without home health coverage. We describe our process for developing and implementing a process for hospital-dispensed blinatumomab, which reduced access barriers for patients.
Haematologica · 2025-11-27
articleOpen accessRelapse of B-cell acute lymphoblastic leukemia (B-ALL) after CD19-targeted chimeric antigen receptor T-cell therapy (CAR19) remains a substantial challenge. Allogeneic hematopoietic cell transplant (HCT) represents an approach for both post-CAR19 relapse prevention and relapse therapy. However, a paucity of detailed HCT safety and outcome data exists in this population. We conducted a retrospective review of 47 children and young adults with B-ALL who underwent first HCT for post-CAR19 remission consolidation (preemptive cohort, n=26) or relapse therapy (relapse cohort, n=21). With a median follow-up of 4.1 years, 3-year disease-free survival was 90% in the preemptive cohort and 64% in the relapse cohort. Overall survival, cumulative incidence of relapse, and non-relapse mortality at 3 years were 95%, 5%, and 5% in the preemptive cohort, respectively, and 67%, 20%, and 15% in the relapse cohort, respectively. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 14% in the preemptive and 19% in the relapse cohort. Chronic GVHD developed in 24% and 14% of patients alive at 100 days in the preemptive and relapse cohorts, respectively. Veno-occlusive disease/sinusoidal obstruction syndrome was the most common non-GVHD severe organ toxicity, with a cumulative incidence of 10% in the preemptive and 31% in the relapse cohort. In appropriate patients, HCT can be an effective strategy for attaining durable B-ALL remission when used preemptively post-CAR19 or as part of post-CAR19 relapse salvage therapy.
Blood · 2025-11-03
articleAbstract Introduction Clinical outcomes of children, adolescents and young adults (CAYA) with second or greater relapsed or refractory (r/r) acute myeloid leukemia (AML) are dismal. Current salvage approaches are ineffective, highlighting an urgent need for novel therapies in this population. Investigation of an autologous 4-1BB CD123-directed CAR (CART123) in adults with r/r AML yielded responses in 25% (PMID 39333315). We now report initial safety and preliminary efficacy from a pediatric phase I clinical trial (NCT04678336) evaluating CART123 in a CAYA population with r/r AML. Methods Patients received a single infusion of CART123 following administration of lymphodepleting chemotherapy (LD). We first evaluated a dose level (DL) of 2 x106 CART123 cells/kg (DL1), and after safety was demonstrated in 6 patients, amended to a 3+3 dose escalation design, exploring a higher dose of 5 x106 CART123 cells/kg (DL2). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded using consensus guidelines. Protocol-defined dose-limiting toxicities (DLTs) included prolonged grade 3 CRS, ICANS, and non-hematologic toxicities. Bone marrow (BM) evaluation was performed on day 28 to assess morphologic response, minimal residual disease (MRD) by flow cytometry and potential on-target/off-tumor myeloid aplasia. CART123 expansion was assessed in peripheral blood (PB) using quantitative polymerase chain reaction and serum cytokines were assessed by a Luminex multiplex immunoassay. Results Twelve patients were screened, 10 enrolled, and 9 had successful generation of CART123 products meeting target dose. One subject withdrew consent prior to CART123 manufacture, and 2 died of progressive disease prior to infusion. Seven patients were infused with CART123 between June 2021 and September 2024 (6 at DL1, 1 at DL2). Median age at infusion was 5 years (range 3-27), 2 (29%) were female, 1 (14%) was of Hispanic ethnicity, and 4 (56%) non-Hispanic patients were of non-white race. LD regimens included fludarabine and cyclophosphamide with (n=3) or without (n=4) azacitidine. All infused patients had highly refractory disease, with a median of 5 prior lines of treatment (range 3-10), and a median pre-infusion BM blast burden of 50% (range 0-95%). CD123 antigen expression on AML blasts was positive in 6 and negative in 1. DL1: All 6 (100%) patients treated at DL1 experienced CRS (grade 1 or 2 in 5, grade 4 in 1). No ICANS was observed and no DLTs were identified. Although CART123 proliferation occurred with a median peak detection in PB of 7,314 copies/µg genomic DNA (gDNA) (range 28-120,818), CART123 was undetectable by day 28 in 3/5 assessed patients. There were no clinical responses at this dose level. CD123 expression was retained on AML blasts in 5/5 patients with pre-infusion antigen positivity. DL2: The patient treated at DL2 experienced grade 4 CRS and grade 3 ICANS, both deemed DLTs due to duration, and both fully resolved by day 10 following infusion. Treatment for toxicity included tocilizumab, steroids and anakinra. Cytokine profiling demonstrated early elevation of IL-6, IFN-gamma, CXCL9 and GM-CSF. Upon resolution of CRS, the patient developed leukocytosis driven by emergence of PB blasts, with absolute blast count rising to 9,570/µL by day 10 following CART123 infusion. The patient then developed progressive monocytosis, with absolute monocyte count rising to a maximum of 25,280/µL on day 18, coinciding with disappearance of PB blasts. CART123 expansion peaked at 10,816 copies/µg gDNA on day 20, with ongoing detection in PB on day 28. This patient achieved an MRD-negative complete response with partial recovery of platelet count (CRp) on day 28 and proceeded to hematopoietic stem cell transplant (HSCT). Following HSCT, 100% donor chimerism was achieved, however, the patient relapsed on day +145 and died due to disease progression on day +174 post-HSCT. Conclusions CART123 manufacture is feasible in heavily pre-treated CAYA patients with r/r AML. For the patient treated at the higher dose, CART123 appeared to induce monocytic differentiation of AML blasts, and day 28 response of CRp facilitated consolidative HSCT. Detailed molecular characterization is underway to better understand response mechanisms. Future investigation of CART123 will continue dose exploration and evaluate co-therapy with cytokine blockade.
Pediatric Blood & Cancer · 2025-01-23 · 1 citations
reviewChimeric antigen receptor (CAR) T-cell therapy is a potentially life-saving treatment for children with relapsed/refractory B-cell hematologic malignancies, and remains an important investigational therapy for other childhood cancers. Yet, access to this class of therapies remains suboptimal through both commercial use and clinical trials, especially in children, adolescents, and young adults. Using a series of case-based discussions, we outline guidance on real-world medical decision-making, and offer potential solutions to enhancing access to CAR T-cell therapy as a treatment modality.
Nature Communications · 2025-04-23 · 12 citations
articleOpen accessAbstract Antigen escape relapse is a major challenge in targeted immunotherapies, including CD19- and CD22-directed chimeric antigen receptor (CAR) T-cell for B-cell acute lymphoblastic leukemia (B-ALL). To identify tumor-intrinsic factors driving antigen loss, we perform single-cell analyses on 61 B-ALL patient samples treated with CAR T cells. Here we show that low levels of IKAROS in pro-B-like B-ALL cells before CAR T treatment correlate with antigen escape. IKAROS low B-ALL cells undergo epigenetic and transcriptional changes that diminish B-cell identity, making them resemble progenitor cells. This shift leads to reduced CD19 and CD22 surface expression. We demonstrate that CD19 and CD22 expression is IKAROS dose-dependent and reversible. Furthermore, IKAROS low cells exhibit higher resistance to CD19- and CD22-targeted therapies. These findings establish a role for IKAROS as a regulator of antigens targeted by widely used immunotherapies and in the risk of antigen escape relapse, identifying it as a potential prognostic target.
Journal for ImmunoTherapy of Cancer · 2025-04-01 · 17 citations
articleOpen accessBACKGROUND: Relapse of B-cell acute lymphoblastic leukemia (B-ALL) with CD19-antigen loss after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a dismal prognosis. Novel immunotherapeutic strategies for this patient population are urgently needed. METHODS: We tested a novel, fully human anti-CD22/4-1BB CAR T-cell construct, CART22-65s, in parallel phase I studies for pediatric and adult B-ALL. After lymphodepletion, CART22-65s was infused using a 3-day fractionated dosing scheme, allowing for omission of the second and third doses in cases of early cytokine release syndrome (CRS). RESULTS: Twenty-two patients, all with relapse after prior CD19-directed immunotherapy, were enrolled. Of 19 infused patients (pediatric, n=17; adult, n=2), 14 (74%) achieved a complete remission (CR), including 4 of 6 (67%) patients refractory to prior inotuzumab. Five of 14 patients in a CR proceeded to consolidative hematopoietic cell transplantation (HCT). With a median follow-up of 38 months, the 12-month relapse-free survival rate was 38.4% (95% CI 19.3% to 76.5%) and overall survival rate was 52.6% (95% CI 34.3% to 80.6%). Two patients received additional CART22-65s treatments for subsequent CD22-positive relapses; one achieved another CR. All CRS (n=17, 89%) and neurotoxicity (n=4, 21%) events after initial infusion were grades 1-2. The only grade 3 CRS/neurotoxicity and the only high-grade immune effector cell-associated hemophagocytic lymphohistocytosis-like syndrome occurred in the retreatment setting. In vivo cellular kinetic data revealed robust CART22-65s proliferation by quantitative PCR peaking at a median of 20 days postinfusion, with the cells persisting out to month 42 in one patient who achieved a long-term remission with CART22-65s alone. CONCLUSIONS: The favorable safety profile and high remission rates in exceedingly refractory B-ALL support the continued development of CART22-65s but also highlight the need to use the product in combination with HCT or other novel strategies. TRIAL REGISTRATION NUMBERS: NCT02650414 and NCT03620058.
Blood · 2025-11-03
articleAbstract Introduction: The Children's Oncology Group (COG) Trial AALL1731 demonstrated a remarkable reduction in relapse risk with the addition of blinatumomab to the standard frontline chemotherapy backbone for pediatric B-cell acute lymphoblastic leukemia (B-ALL). These results, along with recent FDA approval for pediatric patients, fundamentally altered the treatment paradigm such that blinatumomab is now considered a new standard of care. However, successful delivery of blinatumomab is made challenging by its administration as a 28-day continuous intravenous infusion, associated requirement for drug bag replacements at variable intervals dependent on institutional clinic capacity and homecare service availability, and complex insurance reimbursement. In this analysis, we sought to characterize the real-world landscape of pediatric blinatumomab care delivery in the United States (US) from the perspective of treating centers. Methods: We administered a 28-question REDCap survey to US COG institutions from February-March 2025 assessing each institution's clinical practice with blinatumomab. Care delivery barriers (i.e. toxicity concerns, insurance coverage, lack of homecare, institutional challenges, pharmacy staffing, nursing staffing, family declining, family distance, limited family resources, limited non-English resources) were reported using a 5-point Likert scale rating each barrier's impact on their ability to deliver blinatumomab outpatient. For this analysis, a barrier was considered major if an institution rated it ≥4. Descriptive frequencies and statistics were tabulated. We compared the most frequently reported major barriers by site characteristics (US census region, site-reported annual ALL volume, site-reported years of experience with blinatumomab, COG-verified experience with blinatumomab measured by number of AALL1731 blinatumomab-arm enrollments) using chi-square tests. We examined characteristics of institutions who were not administering blinatumomab to populations with specific challenges: infant (delivery challenges associated with low weight) and Ph+ (not part of the FDA approval) ALL. Results: Of 195 active US COG institutions, 149 completed the survey (76% response rate) representing 44 states and Puerto Rico. More than 90% of centers reported utilizing blinatumomab as their institutional standard of care for standard risk (SR)-average, SR-high, and high risk (HR) B-ALL. Fewer centers reported utilizing blinatumomab for infant (56%) and Ph+ (65%) B-ALL. Centers not utilizing blinatumomab for infants were more likely to be small volume i.e. <10 ALL cases per year (39% vs. 16%, p<0.001), have no history of AALL1731 blinatumomab-arm enrollments (20% vs. 6%, p=0.007), and have <5 years of prior experience with blinatumomab (42% vs. 18%, p=0.002). Similar patterns were observed for Ph+ ALL. Most centers (62%) reported at least one major care delivery barrier in the outpatient setting with 36% reporting ≥3. The most frequently reported barriers were lack of homecare companies (50%), family distance to treating center (28%), and insurance coverage for homecare (26%). Compared to the Midwest (44%) and South (43%) census regions, centers based in the Northeast (61%) and West (71%, p=0.07) trended towards having more issues with lack of homecare companies. Lack of homecare companies did not otherwise differ by site characteristics. Centers not utilizing blinatumomab for infant (60% vs. 43%, p=0.06) and Ph+ ALL (67% vs. 41%, p=0.002) were more likely to lack homecare companies. Conclusion: Despite its complex care delivery requirements, the majority of COG institutions have quickly adapted to blinatumomab as frontline standard of care for most higher risk pediatric B-ALL subgroups following AALL1731 trial results and FDA approval. However, there is substantial heterogeneity in infant and Ph+ ALL. Issues related to homecare (lack of companies, insurance coverage, and family distance to treating center) are a predominant theme of current challenges. The national variability in pediatric homecare is an important health system issue given potential implications for blinatumomab-related family burden in terms of inpatient admissions and emergency room visits, resource burden on hospitals, and our ability to implement large-scale pediatric outpatient care delivery beyond blinatumomab.
Blood · 2025-11-03
articleAbstract Background CD19-directed chimeric antigen receptor T-cell (CART19) therapy has transformed the treatment landscape for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Yet relapse occurs in approximately 50% of recipients. These patients and subgroups of pediatric patients in first relapse, currently ineligible for commercial CART19, have very poor outcomes with current approaches, warranting investigation of alternative strategies. We previously investigated a humanized CART19 (huCART19) in a Phase I trial with encouraging responses in both CAR-naïve and CAR-exposed cohorts (Myers JCO 2021). Here we report outcomes from a Phase II clinical trial (NCT03792633) of huCART19 for high risk r/r B-ALL, including early bone marrow (BM) relapse, a subgroup with historically poor outcomes despite intensive therapy. Methods Patients aged 0-29 years (y) with CD19+ B-ALL were eligible in 2 cohorts: CAR-naïve patients with B-ALL that is refractory, in high risk first relapse, second or greater relapse, or relapsed after or ineligible for hematopoietic stem cell transplant (HSCT); CAR-exposed patients with poor response to prior cell therapy. Patients received huCART19 at a dose of 5x106 CAR T cells/kg (maximum 2.5x108) after lymphodepletion (LD) with fludarabine and cyclophosphamide. Response was assessed on day 28 by BM and cerebrospinal fluid morphology, minimal residual disease (MRD) by flow cytometry, and biologic response by B cell aplasia (BCA). The primary endpoint was event-free survival (EFS). Secondary endpoints included overall response rate (ORR), defined as rate of complete remission (CR) or CR with incomplete hematologic recovery (CRi) with BCA, and relapse-free survival (RFS). Data cutoff was July 1, 2025. Results Of 106 patients enrolled, 100 were infused with huCART19 from 3/2019-8/2023. The median age at infusion was 12y (range 1-29), 44% were female, 20% Hispanic, 5% Asian, 7% Black, and 6% had Trisomy 21. Prior therapy included HSCT in 21%, blinatumomab in 21% and inotuzumab in 15%. The CAR-naïve cohort (n=52) included 25 with first early BM relapse within 36m of diagnosis (12 <18m). On pre-infusion BM performed post-LD, 13/52 (25%) had >25% blasts, 25/52 (48%) <0.01%. Three patients were inevaluable for response: 1 deemed ineligible due to myeloid lineage switch on pre-infusion BM; 1 died on day 2; 1 lost to follow-up at day 28. By day 28, 46/49 (94%) were in CR/CRi, 45/46 MRD-negative, 1 MRD inevaluable. With a median follow up of 51m, EFS and RFS at 2y were 65% (95% CI 52-81%) and 70% (95% CI 57-86%), and at 4y, 57% (95% CI 42-76%) and 62% (95% CI 47-81%). Relapse occurred in 14/46 (30%), of which 7 (50%) were CD19-. Ten patients pursued alternative therapy in remission, 7 for loss of BCA and 3 for MRD recurrence (2 CD19+, 1 CD19-). Overall survival (OS) at 2y and 4y was 74% (95% CI 63-87%). In a subgroup analysis of CAR-naïve patients treated for early BM relapse, ORR was 21/23 (91%), 2y EFS was 39% (95% CI 21-72%), RFS 45% (95% CI 25-81%), and OS 57% (95% CI 40-81%). The CAR-exposed cohort (n=48) included 20 with post-CART19 relapse and 28 with early (<6m) loss of BCA without relapse. On pre-infusion BM, 5/48 (10%) had >25% blasts, 34/48 (71%) <0.01%. By day 28, 43/48 patients were in CR/CRi, 43/43 MRD-negative; 6/43 did not establish BCA resulting in an ORR of 37/48 (77%). With a median follow up of 43m, EFS and RFS at 2y were 53% (95% CI 39-71%) and 72% (95% CI 57-91%), and at 4y, 50% (95% CI 36-68%) and 68% (95% CI 52-88%). Relapse occurred in 9/37 (24%), of which 4 (44%) were CD19-. Eleven patients received alternative therapy in remission, 6 for loss of BCA, 4 for CD19+ MRD recurrence, and 1 for therapy-related myeloid neoplasm. OS at 2y and 4y was 77% (95% CI 66-90%). CRS was reported in 47/52 (90%, 10 grade [Gr] 3, 5 Gr 4 on Penn scale) CAR-naïve patients and 38/48 (79%, 1 Gr 3, 2 Gr 4) CAR-exposed. There was 1 death prior to day 28, due to gastrointestinal hemorrhage on day 2 in the setting of progressive ALL and Gr 2 CRS. CAR neurotoxicity was reported in 14/52 (27%, 2 Gr 3, 2 Gr 4) CAR-naïve patients and 7/48 (15%, 1 Gr 3, 1 Gr 4) CAR-exposed, with 1 case of Gr 3 cerebral edema, fully recovered, and 1 case of ongoing myelopathy. Conclusions HuCART19 produced durable remissions in high risk r/r B-ALL and demonstrated efficacy as salvage therapy for those with poor response to prior CAR therapy, comparing favorably to historical outcomes in this extremely high risk group.
CD19 CAR T cell therapy is an effective strategy for first CNS relapse in pediatric b ALL
Blood · 2025-11-03 · 1 citations
articleOpen accessAbstract Introduction: The 4-year disease-free survival (DFS) of children with first isolated central nervous system (iCNS) relapse treated on the most recent Children's Oncology Group AALL1331 randomized phase 3 trial was extremely poor at 24%, and the addition of blinatumomab failed to improve outcomes. Cranial radiation (cXRT) is the standard of care (SOC) for CNS relapse but can have profound neurologic consequences. More effective and less toxic strategies are urgently needed. We hypothesized that CD19-targeted CAR T cell therapy (CART19) could lead to durable remissions in patients with CNS-relapsed B-ALL and obviate the need for cXRT or hematopoietic cell transplant (HCT). We conducted a Phase 2 trial of CTL019, the construct that was FDA approved as tisagenlecleucel, for this population (NCT04276870). Methods: Patients 0-29 years (y) of age with CNS relapse of B-ALL without receipt of cXRT for this relapse were lymphodepleted with fludarabine/cyclophosphamide prior to infusion with 5x106 CART19 cells/kg. Results: From March 2020 to April 2025, 43 patients were enrolled and infused with CART19; 39 (91%) had first CNS relapse (3 second, 1 third). Thirty-six patients (84%) had iCNS relapse. Median age at infusion was 8y (range 1-26y); 44% were female. Six (14%) patients were Hispanic; of those not Hispanic, 72% were White, 11% other, 8% Black, 6% unknown, 3% Asian. Only the 4 patients in ≥2nd relapse had received prior cXRT and/or total body irradiation (TBI). Ten (23%) received prior blinatumomab. At infusion, 6 patients (14%) had marrow disease, 8 patients (19%) had CNS2 disease (cerebrospinal fluid (CSF) white blood cell count (WBC) <5 with blasts), and 2 (5%) had CNS disease by imaging. No patients had CNS3 disease by CSF evaluation (CSF WBC ≥5 with blasts). Of the 42 evaluable patients 28 days after CART19 infusion, 41 (98%) were in CNS remission, and all with marrow disease at infusion were MRD negative. One patient was CNS2 at day 28 and cleared at month 2 without intervention for a best overall response rate of 100%. With a median follow-up of 12 months (m) and mean of 22m (range 1-55m), 1y and 2y EFS were both 90% (95% CI 81-100%) when censoring for alternative therapy. Shorter CART19 persistence, as evidenced by B-cell recovery (BCR), led to 12 patients pursuing other therapy (HCT, n=2; other CART, n=10). EFS without censoring for alternative therapy was 90% (95% CI 81-100%) at 1y and 85% (95% CI 73-99%) at 2y. Among the 14 patients with >4 years of potential follow-up time at data cutoff, 4y EFS was 65% (95% CI 42-100%) and 71% (95% CI 51-99%) with and without censoring for alternative therapy, respectively, and OS was 93% (95% CI 80-100%). Four patients experienced morphologic relapse (1 medullary, 1 combined, 1 CNS2, 1 lineage switch); 2 had MRD-level relapse. Four relapses were CD19 positive, and 2 were CD19 negative. Three patients were successfully bridged to HCT, 1 went to other CART, and 2 were being bridged to HCT at the time of data cut off. All 5 patients who went to HCT after CART19 (early BCR, n=2; relapse, n=3) received TBI; all other patients avoided cXRT. Overall survival (OS) at 1y was 100% and 90% (95% CI 78-100%) at 2y. CART19 proliferation by qPCR in peripheral blood peaked at a median of 9 days (range 6-14) post-infusion with a median of 31,620 copies/μg genomic DNA. CART19 was detectable by qPCR in CSF at day 28 in 98% of evaluable patients. Manufacturing optimization reduced the cumulative incidence of early BCR at 6m from 67% (95% CI 35-85%) for the first 16 patients treated to 39% (95% CI 19-59%) for the subsequent 27 patients treated after the changes, representing enhanced CART19 persistence. Cytokine release syndrome (CRS) was observed in 33 patients (77%) after initial infusion, only 2 of which had higher grade events (1 grade 2; 1 grade 4). Four patients (93%) had grade 3 neurotoxicity events: focal cerebral edema, seizure, and encephalopathy (n=2). All fully recovered; no grade 4 or 5 toxicity occurred. Conclusions:In this Phase 2 trial, CART19 achieved an 85% 2-year EFS in CNS-relapsed B-ALL with 88% (38/43) of patients avoiding toxic cranial radiation, the SOC for CNS relapse for decades. While longer follow-up is needed, the 4y EFS of 71% and OS of 93% in the 14 patients with 4+ years of follow-up is promising and is superior to the outcomes on AALL1331. This study demonstrates that CART19 is an effective and less toxic strategy for ≥1st CNS relapse of pediatric B-ALL.
Frequent coauthors
- 131 shared
Stephan A. Grupp
Children's Hospital of Philadelphia
- 111 shared
Shannon L. Maude
University of Pennsylvania
- 111 shared
Regina M. Myers
Children's Hospital of Philadelphia
- 85 shared
Amanda M. DiNofia
University of Pennsylvania
- 83 shared
David T. Teachey
Children's Hospital of Philadelphia
- 77 shared
Richard Aplenc
Hospital for Sick Children
- 57 shared
Yimei Li
Children's Hospital of Philadelphia
- 55 shared
Caroline Diorio
Children's Hospital of Philadelphia
Labs
Leahy LabPI
Education
- 2005
B.A., Russian Language Major, Chemistry Minor
Bowdoin College
- 2008
M.A., Biological Sciences
Hunter College of the City of New York
- 2012
M.D.
SUNY Upstate Medical University
- 2020
Other
University of Pennsylvania
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