Amanda DiNofia
· Assistant Professor of Clinical Pediatrics (Oncology)VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 2012–2026
About
Amanda DiNofia, MD, MSCE, is an Assistant Professor of Clinical Pediatrics (Oncology) at the Perelman School of Medicine at the University of Pennsylvania. She holds a B.S. in Biology from Ursinus College, an M.D. from Drexel University, and an M.S.C.E. in Clinical Epidemiology from the University of Pennsylvania. Her professional roles include serving as the Associate Chief Clinical Research Officer at the Research Institute of the Children's Hospital of Philadelphia, as well as the Associate Director of Cellular Immunotherapy Clinical Operations in the Cell Therapy and Transplant Section of the Division of Oncology at the same hospital. She is a full member of the Abramson Cancer Center at the University of Pennsylvania. Her research and clinical focus involve cellular immunotherapy, particularly in pediatric oncology, with extensive involvement in CAR T-cell therapy and related immunotherapeutic strategies for leukemia and other hematologic malignancies.
Research signals
Five dimensions sourced from public faculty / publication signals. Sign in to compare against your own profile and see your match score.
Research topics
- Medicine
- Internal medicine
- Immunology
- Bioinformatics
- Biology
- Oncology
Selected publications
Blood Advances · 2026-02-17 · 1 citations
articleOpen accessABSTRACT: CD19 chimeric antigen receptor T cells (CD19-CAR) are effective at eradicating bone marrow (BM) B-cell acute lymphoblastic leukemia (B-ALL), but efficacy data for the treatment of extramedullary leukemia are lacking. We conducted a multisite, retrospective review of 308 children and young adults who received CD19-CAR and report efficacy in patients with active central nervous system (CNS) disease (CNS cohort, n = 36), active non-CNS extramedullary disease (EMD; n = 21), or isolated BM disease (iBM; n = 251) at infusion. The overall survival (OS) at 24 months in the iBM, EMD, and CNS cohorts was 71.5% (95% confidence interval [CI], 66.0-77.6), 66.7% (95% CI, 49.3-90.2), and 57.0% (95% CI, 42.6-76.3), respectively (P = .032); the corresponding event-free survival (EFS) was 51.8% (95% CI, 45.8-58.6), 45.8% (95% CI, 28.2-74.4), and 35.2% (95% CI, 22.4-55.3) (P = .035). All patients with isolated EMD (n = 5) achieved complete response and did not relapse. Eight patients (80%) with isolated CNS disease (n = 10) had clearing of the CNS, and 3 (37.5%) subsequently relapsed. Concurrent EMD or CNS disease with high BM disease burden (HD) was associated with inferior outcomes when compared with low BM disease burden (LD) in terms of OS (EMD-HD, 41.7% vs EMD-LD, 100%; P = .005; CNS-HD, 33.3% vs CNS-LD, 92.3%; P = .001) and EFS (EMD-HD, 8.3% vs EMD-LD, 100%; P< .001; CNS-HD, 14.3% vs CNS-LD, 63.6%; P< .001). In summary, CD19-CAR may be an effective option for relapsed/refractory B-ALL with active EMD or CNS disease, but concurrent HD predicts inferior outcomes, prompting consideration of enhanced preinfusion evaluation and treatment.
Transplantation and Cellular Therapy · 2026-02-01
articleTransplantation and Cellular Therapy · 2026-02-01
articleCCR4 expression defines a targetable subset of T-cell acute lymphoblastic leukemia
Blood Advances · 2026-02-11 · 1 citations
articleOpen accessABSTRACT: Patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) have a dismal prognosis largely mediated by nonsustained responses to chemotherapy and few targeted therapy options. Surface antigen targets in T-ALL include CD2, CD5, CD7, and CD38; however, ongoing clinical development of these targets is challenged by (1) T-cell fratricide during manufacturing, (2) T-cell depletion during treatment, and (3) high frequency of target-negative relapse. Here, we use a combination of flow cytometry, single-cell genomics, and bulk RNA sequencing to identify CC chemokine receptor type 4 (CCR4) as a novel surface target in T-ALL. We analyzed the T-ALL microenvironment from 40 patients treated on the AALL0434 clinical trial and identified a subpopulation of bone marrow-enriched CCR4+ FOXP3+ T-regulatory cells that express immune checkpoints (PD-1 and TIGIT) and could be targeted with anti-CCR4 therapy. Finally, we describe the preclinical efficacy of an anti-CCR4 chimeric antigen receptor T-cell therapy in in vitro and in vivo models, paving the way for future translational efforts in chemotherapy-refractory T-ALL.
Transplantation and Cellular Therapy · 2026-02-01
articleHemaSphere · 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.
Transplantation and Cellular Therapy · 2025-02-01 · 1 citations
articleJournal 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.
Financial toxicity and association with treatment outcomes during pediatric CAR T therapy.
Journal of Clinical Oncology · 2025-05-28
article10028 Background: Chimeric antigen receptor T cell (CAR) therapy has revolutionized the treatment of relapsed/refractory pediatric B cell malignancies. However, the financial toxicity (FT) experienced by families is unknown despite the likely high burden imposed by clinic visits, hospital admissions, and potential travel/relocation to referral centers. We present the first report of pediatric FT among families of children receiving CAR therapy including prevalence, trajectory, and impact on outcomes. Methods: This is a prospective cohort analysis of patient (pt) and caregiver-reported FT outcomes for pediatric and young adult pts receiving CD19-directed CAR therapy at the Children’s Hospital of Philadelphia. Caregivers (for pts < 18 years old) or pts (if ≥ 18 years old) completed the Comprehensive Score for Financial Toxicity (COST) prior to CAR infusion (baseline), 1 month, and 3 months post-infusion. COST is a self-report FT measure that has been used in adults with specific validated grading criteria (0-3) anchored on independent differences in health-related quality of life. We described baseline FT and tested its association with treatment-related toxicity (occurrence of any cytokine release syndrome [CRS]) and outcomes (complete response [CR] at day 28) using multivariable models adjusted for time from diagnosis, prior CAR exposure, and disease burden at infusion. FT was hypothesized to impact outcomes through physiologic stress affecting immunologic response. In pts with COST data through 3 months, we described longitudinal FT trajectories. Results: From 9/2019-12/2024, 144 pts (33% racial/ethnic minority, 8% public insurance) or their caregivers (28% less than college degree, 22% annual household income < $50,000) completed baseline COST measures. 94% of the cohort had caregiver-reported FT. 81% of pts were external referrals. The median baseline COST score was 20.0 (IQR: 11.0-29.0), which corresponds to Grade 1 FT. Two-thirds of pts reported FT, with 37%, 29%, and < 1% of families experiencing grades 1-3 FT, respectively. 80% of pts had CRS; 89% had CR at day 28. Baseline FT was not associated with CRS or day 28 response (all p > 0.2). A subset of n = 80 had complete longitudinal data and follow up of at least 3 months. In this cohort, median COST score at baseline, month 1, and month 3 was 19.5 (IQR: 10.0-29.3), 18.5 (IQR: 11.0-27.3), 16.0 (IQR: 9.8-27.0), respectively. Strikingly, 23% and 25% of pts had clinically worse grades of FT at 1 month and 3 months post-infusion (compared to baseline), respectively. Race/ethnicity, language, insurance, caregiver education, and income were not associated with worsened FT over time. Conclusions: There is a high prevalence of FT at time of CAR infusion for families of pediatric and young adult pts. Reassuringly, FT at the time of infusion was not associated with two key treatment outcomes, but more investigation is needed. For a notable proportion of families, FT worsens over time and highlights the need for interventions to address cumulative financial burden.
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.
Frequent coauthors
- 115 shared
Stephan A. Grupp
Children's Hospital of Philadelphia
- 105 shared
Shannon L. Maude
University of Pennsylvania
- 95 shared
Regina M. Myers
Children's Hospital of Philadelphia
- 89 shared
Richard Aplenc
Hospital for Sick Children
- 85 shared
Allison Barz Leahy
Children's Hospital of Philadelphia
- 75 shared
David T. Teachey
Children's Hospital of Philadelphia
- 63 shared
Carl H. June
Parker Institute for Cancer Immunotherapy
- 62 shared
Caroline Diorio
Children's Hospital of Philadelphia
Education
- 2004
B.S., Biology
Ursinus College
- 2009
M.D.
Drexel University
- 2016
Other, Clinical Epidemiology
University of Pennsylvania
- Resume-aware match score
- Save to shortlist
- AI-drafted outreach
See your match with Amanda DiNofia
PhdFit ranks faculty by your research interests, methods, and publications — grounded in their actual work, not templates.
- Free to start
- No credit card
- 30-second signup