Dan Toby Vogl

Verified

University of Pennsylvania · Rehabilitation Medicine

Active 1985–2026

h-index60

Citations18.7k

Papers346140 last 5y

Funding$93.9M1 active

Faculty page

See your match with Dan Toby Vogl — sign in to PhdFit.Sign in

About

Dan Toby Vogl, M.D., M.S.C.E., is an Associate Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania and a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine. His clinical expertise includes multiple myeloma, amyloidosis, and bone marrow transplant. His research focuses on epidemiology, clinical trial design, drug development, and translational research.

Research topics

Internal medicine
Medicine
Immunology
Oncology
Cancer research
Pharmacology

Selected publications

Multiple Myeloma, Version 5.2026, NCCN Clinical Practice Guidelines In Oncology
Journal of the National Comprehensive Cancer Network · 2026-01-01 · 3 citations
article
The treatment landscape for multiple myeloma (MM) is evolving rapidly and includes several new options. The management must be tailored to the individual. The NCCN Guidelines for MM provide a framework to base decisions regarding diagnosis, workup, treatment, and follow-up of both newly diagnosed and previously treated relapsed/refractory MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to newly diagnosed MM (NDMM).
Publisher DOI
The ancestral haplotype of P2RX5 yields a B-cell surface marker and a multi-lineage immunotherapy target
bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-14
article
SUMMARY While CD19- and BCMA-directed immunotherapies have improved outcomes for B-lymphoid and plasma cell malignancies, frequent relapses with antigen loss/downregulation highlight the need for new targets. Here, using transcriptomic datasets and newly-developed monoclonal antibodies, we show that P2RX5 , long considered a pseudogene in humans, encodes a stable protein in 80% of individuals of African descent carrying the ancestral haplotype. Like CD19, P2RX5 displays B-cell lineage-restricted expression in normal tissues. Unlike CD19, P2RX5 is expressed not only in B-cell neoplasms, but also in T-cell leukemia (T-ALL) and multiple myeloma (MM). We developed P2RX5-directed bispecific T-cell engagers and CAR T cells, which killed T-ALL cells with no evidence of T-cell fratricide. These agents were non-inferior to FDA-approved CD19- and BCMA-directed immunotherapeutics in cell culture and xenograft models of Burkitt lymphoma and MM, while maintaining potency against CD19- and BCMA-negative variants. Hence, P2RX5 is a unique multi-lineage target for frontline or salvage immunotherapy.
Publisher DOI
CD4+ T cells mediate CAR-T cell-associated immune-related adverse events after BCMA CAR-T cell therapy
Nature Medicine · 2026-01-15 · 2 citations
articleOpen access
Publisher OA PDF DOI
Survival after Chimeric Antigen Receptor T-cell Therapy Is Predicted By Fried’s Frailty Phenotype
Transplantation and Cellular Therapy · 2026-02-01
article
Publisher DOI
Immune effector cell-associated enterocolitis post-BCMA directed CAR T-cell therapy: insights from a multicenter case series
Blood Cancer Journal · 2026-04-28
articleOpen access
Publisher DOI
Fried's frailty phenotype predicts survival in pts with relapsed/refractory lymphoma or myeloma undergoing chimeric antigen receptor T-cell therapy – a prospective, observational Study
Blood · 2025-11-03
articleOpen access
Abstract 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 &gt; 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 &gt;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&lt;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.
Publisher OA PDF DOI
Supplementary Data 2 from A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death–Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma
2025-11-03
articleOpen access
Supplementary Figures and Tables with Legends
Publisher DOI
Rebuilding immunity: Kinetics and clinical impact of immune reconstitution after CAR T-cell therapy in multiple myeloma
Blood · 2025-11-03
articleOpen access
Abstract Introduction: Chimeric antigen receptor T-cell (CART) therapy frequently results in profound B- and T-cell depletion. The dynamics and clinical implications of immune reconstitution (IR) post-CART in multiple myeloma (MM) remain understudied. Methods Single-center retrospective study of 198 MM patients (pts) treated with ide-cel (n=73) or cilta-cel (n=125) between June 2021 and December 2024. Median follow-up was 20.5 months (mo) (ide-cel 30.6 vs cilta-cel 14.1). We analyzed the kinetics of T-cell and immunoglobulin subsets, excluding values after disease progression, and assessed their association with efficacy outcomes, treatment-related toxicities, and infections. Pts who initiated maintenance therapy were censored at the time of maintenance initiation. Kaplan–Meier analyses were used to assess treatment response and survival outcomes. Results This heavily pretreated cohort included 73.7% and 24.7% of pts with triple-refractory and penta-refractory MM, respectively; 18.7% had high-risk cytogenetics. Lymphocyte expansion kinetics differed based on product. In ide-cel-pts the absolute lymphocyte count (ALC) peaked at Day (D) 7 (300 vs 100 cells/μL), whereas cilta-cel peaked at D12 (450 vs 1100 cells/μL) and demonstrated a delayed but greater sustained expansion from D10 to D24 (AUC ide-cel 7,100 vs cilta-cel 11,400; p&lt;0.01; bootstrap 95% CI [–7.6, –1.6]) despite comparable CD4⁺ and CD8⁺ T-cell proportions at apheresis between products (p&gt;0.05). Among ide-cel–pts, a higher CD4⁺ proportion at apheresis trended toward longer PFS, exceeding the product-specific median (p=0.08), while no such association was observed in the cilta-cel group (p&gt;0.5). Profound immunodeficiency at Month (M) 1, defined as CD4⁺ T-cell counts &lt;50/μL, was associated with a significantly shorter PFS (3.2 vs 22.4 mo, p&lt;0.0001). Median CD4⁺ T-cell count recovery (&gt;150 cells/μL) occurred by M6, coinciding with the median time of Trimethoprim/Sulfamethoxazole exposure (5.6 mo [IQR 1.6–10.7]). To assess humoral immune reconstitution, IgM levels were analyzed, excluding pts with IgM-secreting myeloma and censoring those at time of progression. Ide-cel was associated with earlier immunoglobulin recovery (median IgM≠0), typically by M6 (Median IgM: ide-cel 13 mg/dl [IQR: 0-30.5] vs cilta-cel 0 [IQR: 0-19.5], p=0.06), compared to Year (Y) 1 (Median IgM: ide-cel 37 mg/dl [IQR: 21-56] vs cilta-cel 17.5 [IQR: 0-46.8], p=0.02). IgM levels were also significantly higher in ide-cel recipients at M3 (p&lt;0.001). Immune reconstitution was associated with non-M-Spike bands in 20% of pts (12/61 with detectable IgM at M6). Among ide-cel–pts, higher detectable IgM levels at M3 were associated with inferior PFS (median IgM M3: 28 [PFS≤12 mo], 0 [PFS&gt;12 mo], p=0.004). This association was not observed in cilta-cel-pts, likely related to immature follow-up. The infection rate in the cohort was 68.2% (135/198), with 54% resulting in hospitalizations. Median time to first infection was 1.9 mo [IQR: 0.6-4] with a trend toward earlier infection in cilta-cel (1.8 vs 2.5 mo, p=0.06). Pts with undetectable IgM at M3 who did not receive IVIG had a numerically higher risk of infection (72% vs 30%, p=0.15). These findings link prolonged immunoparesis to increased infection risk, supporting the use of IVIG. Indeed, 82.7% (158/191) of pts received IVIG, with a median initiation time of 1.8 mo post-CART. Among them, 47% discontinued IVIG by a median of 9.3 mo. Pts who received IVIG without evidence of immune reconstitution had similar infection and hospitalization rates as those with immune reconstitution (p&gt;0.05 for each comparison). Conclusion: Immune profiling after CART therapy offers opportunities for risk stratification and intervention. A higher CD4⁺ T-cell proportion at apheresis may serve as a predictive biomarker for improved outcomes in ide-cel recipients, informing product selection or apheresis optimization strategies. Early CD4⁺ lymphopenia and rapid IgM recovery were associated with inferior PFS, suggesting that immune profiling at one month may help identify high-risk pts who could benefit from closer monitoring or early intervention. Cilta-cel induces delayed but more durable expansion, contributing to prolonged immunoparesis. The high incidence of infections, particularly among pts with persistent immune deficits and absent IgM, highlights the need for careful monitoring and infectious prophylaxis ie. use of IVIG to mitigate infection-related morbidity.
Publisher OA PDF DOI
Supplemental Figure from A Phase I/II Open-Label Study of Molibresib for the Treatment of Relapsed/Refractory Hematologic Malignancies
2025-11-25
articleOpen access
Supplemental Figure
Publisher DOI
Supplementary Tables and Figures from Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy
2025-11-24
articleOpen access
Supplemental tables: (1) Subject characteristics. (2) Cytogenetic profiles and high-risk features. (3) Prior treatment exposures and refractoriness. (4) CAR T cell product characteristics. (5) Products that did not meet target dose. (6) Adverse events of grade 3-4. (7) Cytokine release syndrome and ICANS. (8). Maintenance therapy. Supplemental Figures: (1) Study schematic and subject disposition, (2) Correlates of manufacturing success, (3) Hematopoietic recovery, (4) Post-infusion T cell phenotypes, (5) Correlates of in vivo expansion and manufacturing success, (6) Late post-infusion CAR T cell re-expansion, (7) Soluble BCMA, (8) Late-onset clinical responses, (9) MM cell BCMA expression, (10) Pre- and post-treatment Sox2-specific T cell responses in CART-BCMA monotherapy patients, (11) Pre- and post-treatment Sox2-specific T cell responses in CART-BCMA + huCART19 combination therapy patients, (12) Sustained post-treatment SOX2-specific T-cell responses.
Publisher DOI