Alexander Edward Perl
· MD, MSVerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 2004–2026
About
Alexander Edward Perl, MD, MS, is an Associate Professor of Medicine in the Division of Hematology-Oncology at the Perelman School of Medicine at the University of Pennsylvania. He specializes in the care of patients with acute leukemia, including AML, ALL, myelodysplastic syndromes, and CML. His research focuses on molecularly-targeted therapeutics for acute leukemia, with principal expertise in FLT3 inhibitors for AML. He has played a leading role in clinical trials of these agents and studies other signal transduction targeting agents such as tyrosine kinase inhibitors for Ph-like ALL and inhibitors of oncogenic PI3K/AKT/mTOR signaling. His laboratory has developed methods to quantify pharmacodynamic responses to signal transduction inhibitors and performed preclinical drug screening in cellular and murine models of acute leukemia.
Research signals
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Research topics
- Internal medicine
- Medicine
- Gastroenterology
- Intensive care medicine
- Pathology
- Oncology
- Surgery
Selected publications
Survival after Chimeric Antigen Receptor T-cell Therapy Is Predicted By Fried’s Frailty Phenotype
Transplantation and Cellular Therapy · 2026-02-01
articleHaematologica · 2026-04-01
articleOpen accessErratum to: "Impact of hematopoietic cell transplantation and quizartinib in newly diagnosed patients with acute myeloid leukemia and FMS-like tyrosine kinase 3-internal tandem duplications in the QuANTUM-First trial"
Transplantation and Cellular Therapy · 2026-02-01
articleBlood Advances · 2026-04-08
articleOpen accessQuANTUM-First (NCT02668653) demonstrated improved overall survival (OS) in FLT3-ITD-positive patients with newly diagnosed acute myeloid leukemia (ndAML) treated with quizartinib plus standard chemotherapy. Herein, we evaluated the impact of post-consolidation/post-transplant single-agent maintenance therapy on clinical outcomes in patients receiving maintenance, focusing on measurable residual disease (MRD) status at maintenance onset. Overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were prespecified exploratory analyses. Cumulative incidence of relapse (CIR), analyses by allogeneic hematopoietic stem cell transplant (allo-HCT), and analyses by MRD status were post-hoc and not powered for statistical significance. Samples for FLT3-ITD MRD analysis were collected in composite complete remission patients ≤30 days before receiving maintenance and assessed by an ultrasensitive amplicon-based assay. More transplanted quizartinib-treated patients received maintenance (71%) vs placebo (55%); OS benefit was not demonstrated among these patients. In patients who did not undergo allo-HCT, quizartinib maintenance was associated with a significant OS benefit (HR 0.401; 95% CI, 0.192-0.838), including a benefit in patients who were MRD-negative at the start of maintenance (OS HR of 0.194, 95% CI, 0.056-0.676). Patients who were MRD-negative at the completion of consolidation achieved 89.1% (95% CI, 70.0%-96.4%) survival at 3 years with quizartinib maintenance in the absence of allo-HCT. These data suggest that for patients who achieve FLT3-ITD MRD negativity after induction and consolidation with quizartinib, maintenance with quizartinib provides a significant survival benefit and in some patients may eliminate the need for allo-HCT.
Leukemia Research · 2026-03-21
articleArchives of Pathology & Laboratory Medicine · 2025-09-02
articleOpen accessContext.—: The phase 3 study Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML) (QuANTUM-First; NCT02668653) demonstrated improved overall survival (OS) in newly diagnosed patients with FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication-positive AML treated with the FLT3 inhibitor quizartinib over placebo, leading to the approval of quizartinib in this population. Objective.—: To describe the bridging study between the Navigate clinical trial assay (CTA) used for patient selection in QuANTUM-First and the LeukoStrat CDx [companion diagnostic] FLT3 Mutation Assay, necessary to establish concordance between these 2 assays to support the QuANTUM-First supplemental premarket application for the CDx. Design.—: Assay agreement was established if lower bounds of the 95% CI for both positive and negative percentage agreement were 90% or greater. Treatment efficacy was evaluated to assess if OS in the intent-to-treat (ITT) CDx+ population (CTA+, CDx+) and the QuANTUM-First ITT were comparable. Results.—: The lower bounds of the 95% CI were greater than 90% for positive percentage agreement (94.7%) and negative percentage agreement (100%) based on results from 1029 patients, demonstrating agreement between CTA and CDx. The OS benefit provided by quizartinib in the ITT CDx+ population in the bridging study, with a median OS of 29.4 months for quizartinib versus 14.8 months for placebo (hazard ratio, 0.794; 2-sided stratified log-rank P = .06), was comparable with the OS benefit in the QuANTUM-First ITT. Conclusions.—: The LeukoStrat CDx FLT3 Mutation Assay aids in selecting newly diagnosed patients with FLT3 internal tandem duplication-positive AML for quizartinib therapy.
Blood · 2025-11-03
articleOpen accessAbstract Chimeric antigen T-cell receptor (CART) therapy is highly effective for pts (pts) with relapsed/refractory (R/R) lymphoma/multiple myeloma (MM). However, due to concerns regarding tolerability, older pts are underrepresented in CART trials and real-world studies indicate that CART is underutilized in older adults. Methods to assess fitness for CART are ECOG, clinician gestalt and age. There is interest in improving risk stratification of older adults using objective measures. Fried's frailty phenotype (FP) uses subjective (exhaustion, reported weight loss, activity level) and objective (gait speed, grip strength) measures to categorize pts into fit, pre-frail, and frail. We have previously shown that FP predicts for overall survival (OS) in older stem cell transplant (SCT) recipients. We hypothesize that FP will be associated with progression-free survival (PFS) and OS in older pts with lymphoma/MM undergoing CART therapy. We prospectively enrolled pts ≥ 60 years planned for CART for R/R lymphoma/MM from May 2019 – 2023 on a clinical trial. We performed FP prior to CART infusion, and at 7 days (d), 14d, 21d, 1 month (mo), 3mo, 6mo and 12mo post-infusion. 36 pts were enrolled with a median age at CART infusion of 69 years (Range 60-81). 53% of pts had MM, of whom 63% had intermediate or high-risk disease by R-ISS. The remainder had lymphoma (diffuse large B-cell or follicular lymphoma) with IPI > 2 at diagnosis in 59%. Idecagtagene vicleucel and tisagenlecleucel were the most frequently administered CART products. Median follow up was 33mo. Median prior lines of therapy (LOT) was 3 (Range 1-7) and 47% had prior auto-SCT. Pre-infusion, majority had low ECOG scores (0-1, 81%), including 71% categorized as frail by FP. At pre-infusion FP, 35% of pts were fit (score 0), 44% were prefrail (score 1-2) and 21% were frail (score 3-5). Frail pts were more likely to be admitted for >7d for their CART infusion (OR 7.0, 95% CI 1.02-47.97, p=0.04). Frailty was not associated with risk of CRS, ICANS or 30-day hospital readmission. 13 pts had died by the time of analysis; all but 2 deaths were related to progressive disease. 2 non-disease related deaths were 1 death from COVID and 1 ICANS-related death from teclistamab after relapse 1 year and 2 years after infusion, respectively. At Day 21 post-infusion, 21% were fit, 57% were prefrail, and 21% were frail. At 1mo post-infusion, 25% were fit, 63% were prefrail, and 13% were frail. Being frail by FP at pre-infusion (p<0.001), Day 21 (p=0.03) or 1 month (p=0.009) post-infusion was associated with inferior OS from that time point. Median PFS in pre-infusion fit, prefrail, and frail pts were 23.4mo (95% CI 17.1-NR), 18.4mo (95% CI 6.8-13.8) and 4.0mo (95% CI 2.5-8.4), respectively. 2-year OS estimates were 100%, 93% and 14%, in fit, prefrail and frail pts respectively. 14 of 36 pts maintained or improved their FP from pre-infusion to 1mo; all but 3 received physical therapy (PT) while in hospital with 5 pts continuing PT outpatient. Notably, pts who maintained or improved their FP from pre-infusion to 1mo post-infusion had significantly better OS (p=0.05) than pts who had declines in their scores. Along with pre-infusion, day 21 and 1mo post-infusion FP scores, LDH (Mean 182 U/L) at the time of CART infusion was significantly associated with OS in the univariate Cox proportional hazards model (HR 5.22, 95% CI 1.43-19.18, p=0.013). Several factors including disease type, number of prior lines of therapy, use of bridging, stage at CART, IPI/RISS at diagnosis, HCT-CI, ECOG, presence of extra-nodal disease, CRS, ICANS, gender, age by decade, and BMI did not correlate with outcome. In pts ≥ 60 with R/R lymphoma/MM undergoing CART, 21% were frail by FP prior to CART. Frailty by FP pre-infusion, day 21 and 1mo post-infusion was associated with inferior OS as opposed to ECOG, HCT-CI, age or several disease related risk factors. FP may improve risk stratification in older adults undergoing CART. Pts with improvement in FP within 1mo post-infusion also had better outcomes. While better disease control could contribute to improved FP scores, most pts received PT to reverse frailty. Our future work aims to implement an exercise regimen to improve outcomes and to determine whether frailty is associated with adverse disease biology. Future work to uncover biologic mechanisms of frailty and adverse disease biology may identify novel targets for intervention to improve outcomes for frail pts.
EXABS-176-AML: How to Best Incorporate FLT3 Inhibitors in the Management of FLT3-Mutated AML
Clinical Lymphoma Myeloma & Leukemia · 2025-08-28
article1st authorCorrespondingClinical Lymphoma Myeloma & Leukemia · 2025-08-28
articleBlood · 2025-11-03 · 14 citations
articleOpen accessAbstract Introduction: For decades, standard upfront treatment for acute myeloid leukemia (AML) among fit patients (pts) has been intensive induction chemotherapy (IC), typically with cytarabine and anthracyclines. However, long-term outcomes remain poor, and IC continues to pose substantial short- and long-term morbidities, with significant burden to pts and hospitals. VIALE-A, a phase 3 trial of IC-ineligible pts, established superiority of azacitidine and venetoclax (aza-ven) vs aza alone, with a median OS of 15 months and composite remission rate (CCR) of 66%, which compare favorably to that expected for IC among older pts. We prospectively tested whether aza-ven was superior to IC in fit pts and could challenge the current treatment standard. Methods: This open-label, multicenter, phase II randomized clinical trial compared the therapeutic activity of conventional IC (7+3 regimen or liposomal daunorubicin and cytarabine [CPX351]) to aza-ven among IC-eligible pts aged ≥ 18. Pts with core binding factor fusions, FLT3 mutations, or NPM1 mutations (unless aged ≥ 60) were excluded. The IC arm incorporated cycles of chemotherapy consolidation following induction, for use as clinically appropriate per current standard of care. Pts were allowed to proceed to transplant (HCT) on both arms following response on protocol-directed therapy. The primary endpoint was event free survival (EFS), with events defined as progressive disease, persistent disease prompting therapy change, relapse, hospice, or death. Among secondary endpoints were response rates, OS, toxicity, measurable residual disease (MRD), hospitalization metrics, and quality of life (QOL). Pts were stratified by age (≥ 65 vs < 65) and pre-randomization selection in the IC arm to 7+3 or CPX351. EFS is estimated by Kaplan Meier method and assessed by log rank test and Cox PH regression. Clinical responses are assessed using an exact binomial test. Significance is declared at the two-sided 0.1 type I error. Results: As of 7/25/2025, 172 pts at 9 US centers were randomized to aza-ven (n=86) or IC (n=86), and accrual is complete. Median age was 64 for aza-ven and 65 for IC pts. 55% and 60% were male in the aza-ven and IC arms, respectively, and 65% and 69% were White. The majority of pts were ELN 2022 adverse risk (72%), 15% were intermediate-, and 12% favorable-risk. Distribution of risk categories did not differ across arms (p=0.44), nor did the proportions of TP53, NPM1, or IDH1/2 mutations. Median number of cycles completed were 4 for aza-ven and 2 for IC pts. Among IC pts, 54% received 7+3, and the rest, CPX351. By intent to treat analysis, the rate of overall response (OR=CR+CRh+CRi+PR+MLFS) was significantly higher in the aza-ven arm (88% vs 62%; P<0.001), as was CCR (CR+CRh+CRi) (81% vs 55%; P<0.001). CR rates for aza-ven and IC were not significantly different (59% vs 50%; P=.066). Procession to HCT following response from protocol therapy differed across arms (P=0.009) - 52 (61%) pts on aza-ven and 34 (40%) on IC arms. With a median follow-up of 16 months, 1-year EFS was 53% for aza-ven and 39% for the IC arm. EFS overall was significantly superior in the aza-ven arm (HR 0.61; P=0.017). There was no significant age effect on EFS when included with treatment in the Cox PH model, and HR for treatment remained significant (0.61; P=0.018). Grade (G)3/4 therapy-related adverse events in ≥10% were mainly hematologic and at similar rates across arms. G3/4 lung infections and sepsis occurred in 12% and 7% of aza-ven, and 15% and 11% of IC pts. 30- and 60-day mortality on the aza-ven arm were both 0%, vs 3.5% and 4.7% in the IC arm, respectively. At 2 weeks, aza-ven pts reported significantly better QOL (P=0.001), symptom burden (P=0.019), and depression symptom (P=0.007) scores, vs IC. Aza-ven pts were less likely to need ICU care (0 vs 9.8%; P=0.003), and experienced fewer inpatient days for the index hospitalization (15 vs 36; P<0.001) and during the first 6 months (41 vs 58; P<0.001). Conclusion: The study has met its primary endpoint. Aza-ven was associated with significantly improved EFS, as well as higher rates of OR and CCR, vs IC in younger, IC-eligible pts. Overall survival data continue to mature. A greater proportion of pts successfully went to HCT following response to aza-ven than those to IC. Aza-ven led to numerically fewer serious infectious complications, significantly improved QOL and symptom burden during initial therapy, with less time in the hospital and the ICU.
Recent grants
NIH · $862k · 2015
Frequent coauthors
- 208 shared
Mark J. Levis
- 145 shared
Selina M. Luger
- 101 shared
Martin Carroll
University of Pennsylvania
- 99 shared
Alison W. Loren
University of Pennsylvania
- 76 shared
Richard F. Schlenk
University Hospital Heidelberg
- 76 shared
Giovanni Martinelli
Istituti di Ricovero e Cura a Carattere Scientifico
- 75 shared
Jorge E. Cortés
- 73 shared
Catherine C. Smith
University of Alabama at Birmingham
Education
- 1993
B.A., Psychology
University of Rochester
- 1997
M.D., Internal Medicine
Mount Sinai School of Medicine
- 2011
M.S., Translational Research
University of Pennsylvania
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