About

Adam D Cohen, MD, is an Associate Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania. He serves as the Director of Myeloma Immunotherapy and is a member of the Abramson Cancer Center. Additionally, he co-directs the Amyloidosis Program at the University of Pennsylvania. Dr. Cohen's clinical expertise includes multiple myeloma, amyloidosis, POEMS syndrome, monoclonal gammopathies, and Waldenstrom's Macroglobulinemia. His research focuses on cancer immunotherapy, cellular therapy, phase I trials, and CAR T cell therapies. He has contributed to the field through various publications on outcomes of relapse after teclistamab therapy, B-cell maturation antigen in multiple myeloma, long-term remission after CAR T-cell treatment, and the safety of gene-modified T cell therapies, among others.

Research topics

• Immunology
• Medicine
• Internal medicine
• Oncology
• Cancer research
• Biology
• Gastroenterology
• Pharmacology
• Genetics
• Bioinformatics
• Surgery
• Computational biology

Selected publications

• Rab5 improves CAR T cell efficacy via reducing fratricide and maintaining surface CAR levels

  The Journal of Experimental Medicine · 2026-03-27 · 1 citations

  article

  We show continuous tumor exposure results in a loss of chimeric antigen receptor (CAR) T cell (CART) endocytic activity due to downregulation of Rab5. Loss of endocytic activity exacerbates the effects of trogocytosis, the bidirectional transfer of tumor target antigens and CARs between malignant cells and CARTs, resulting in CART dysfunction and fratricide. Constitutive expression of Rab5 within the CARTs reduced fratricide by reducing the amount of trogocytosed antigens on the cell surface, while simultaneously enhancing CAR availability through dissociation of CAR from target, recycling unbound CAR back to the plasma membrane, and limiting CAR capture by tumor cells. Rab5-expressing CARTs exhibited superior antitumor activity in both BCMA-CARTs isolated from the bone marrow of treated patients and mesothelin-specific CARTs in a solid tumor model. These studies uncover an unexpected relationship between endocytosis and CART function and suggest that pairing Rab5 with CAR expression could improve the clinical efficacy of CART therapy.

  PublisherDOI

• Investigating Associations Between Psychological Distress and Changes in Peripheral Blood Monocytes in Patients With <scp>CLL</scp> / <scp>SLL</scp> Managed With Active Surveillance

  Cancer Medicine · 2026-05-01

  articleOpen access

  Asymptomatic patients with a new diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are commonly managed by active surveillance as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria; however, many patients report elevated distress during surveillance. Psychological distress may have biologic implications given that natural killer [NK] cells, T cells, and monocytes are not only sensitive to distress, but also critical in controlling disease progression. Therefore, the objective of this study was to explore associations of distress with immune biomarkers in patients with CLL/SLL being managed by active surveillance. We enrolled 76 participants and assessed perceived stress, anxiety, and depressive symptoms at study entry and every 6 months for up to 2 years during active surveillance. Blood samples were collected at the same time points to assess biomarkers on T cell, NK cell, and monocyte subsets. In multivariable regression analyses, higher levels of perceived stress and anxiety were significantly associated with lower percentages of intermediate monocytes (IM); anxiety was also significantly associated with higher percentages of classical monocytes (CM). In longitudinal analyses, higher stress and anxiety were significantly associated with higher percentages of CM at 12 months. This is one of the first studies to observe that psychological distress is associated with differential patterns of monocyte distribution in patients with CLL/SLL managed with active surveillance.

  PublisherDOI

• 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
  PublisherDOI

• 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
  PublisherOA PDFDOI

• Predictive biomarkers of response to chimeric antigen receptor (CAR) T-cell therapy for pan-haematologic cancer

  Nature Biomedical Engineering · 2026-03-09 · 4 citations

  article
  PublisherDOI

• Survival after Chimeric Antigen Receptor T-cell Therapy Is Predicted By Fried’s Frailty Phenotype

  Transplantation and Cellular Therapy · 2026-02-01

  article
  PublisherDOI

• Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple myeloma

  Haematologica · 2025-08-28 · 1 citations

  articleOpen access

  Various drug classes target B-cell maturation antigen (BCMA) including chimeric antigen receptor T-cell (CAR T) therapies, bispecific antibodies (bsAb), and antibody-drug conjugates (ADC). Outcomes with CAR T and bsAb therapies in multiple myeloma (MM) have been affected by T-cell exhaustion, and abrogated expression/mutation of the BCMA target has been observed with anti-BCMA therapies. Optimal anti-BCMA sequencing strategies are needed to improve long-term clinical outcomes. We used data from multiple clinical studies of the ADC belantamab mafodotin (as monotherapy and combination regimens) to explore its impact on BCMA levels and binding (using electrochemiluminescence methodology) and T-cell/ natural killer (NK) cell fitness (including cell counts, expression of functional markers), to determine whether belantamab mafodotin could be sequenced ahead of other BCMA-targeting therapies for MM. Levels of free soluble BCMA (sBCMA), measured at the best-confirmed response (BCR) and at progression, dropped at BCR but returned to near baseline at time of disease progression. There was no apparent impact on the binding epitope of BCMA, as indicated by the retention of belantamab mafodotin binding to sBCMA. No significant changes in cell counts or expression of T-cell exhaustion markers (PD-1, TIGIT, TIM-3 [except NK cells], or CTLA-4) and co-stimulatory markers (ICOS [except CD4+ T cells], OX40, 4-1BB) were observed at relevant time points (up to 4 or 21+ months depending on the marker). No negative impact was observed on expression of proliferation (Ki67) and antitumor activity (granzyme B, CD107a) markers. Pending confirmatory studies, our results indicate potential for utilizing belantamab mafodotin ahead of other anti-BCMA therapies in MM.

  PublisherOA PDFDOI

• Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy: Preliminary Safety and Efficacy Data from the “STEM” (Sequential T Cell-Engagement for Myeloma) Trial

  Clinical Lymphoma Myeloma & Leukemia · 2025-09-01

  article1st authorCorresponding
  PublisherDOI

• Access and outcomes of racial and ethnic minority populations receiving commercial anti-BCMA CART for myeloma

  Blood Immunology & Cellular Therapy · 2025-07-16 · 4 citations

  articleOpen access

  • REMPs have reduced access to CART-BCMA therapies for MM. • Clinical outcomes of both approved CART-BCMA products are comparable between REMP and non-REMP patients, despite disparities in access. Chimeric antigen receptor T-cell (CART) therapy targeting B-cell maturation antigen (CART-BCMA) is a transformative treatment for multiple myeloma (MM). However, its high cost and the need for specialized centers may limit access for racial and ethnic minority populations (REMPs), who are more affected by MM. This retrospective cohort study evaluated access and outcomes according to REMP status for 140 patients treated with CART-BCMA for MM (June 2021 to February 2024) at the Abramson Cancer Center (ACC) of the University of Pennsylvania. These patients were compared to 3 control cohorts: 3298 patients with MM from the ACC catchment area; 288 patients with MM treated at the ACC (ACC MM cohort); and 115 patients with MM who would have been eligible for CART (ACC MM CART-eligible cohort). The proportion of REMPs declined across cohorts (catchment area, 33.9%; ACC MM cohort, 28.1%; ACC MM CART-eligible cohort, 26.1%; CART cohort, 17.1%; P < .05). REMP patients receiving CART-BCMA were more likely to live closer to the ACC and were less likely to be married compared to non-REMP patients ( P < .05). Nevertheless, clinical outcomes were similar, with comparable rates of very good partial response (REMP, 75%; non-REMP, 72%; P = .47), progression-free survival ( P = .30), and overall survival ( P = .73), both in the whole cohort and in subgroup analyses based on the product used. Similarly, safety profiles showed no significant differences in cytokine release syndrome, neurotoxicity, and long-term hematologic toxicities. In conclusion, REMPs have reduced access to CART-BCMA but show similar clinical outcomes with both approved CART-BCMA products, highlighting the need to improve equity in access.

  PublisherDOI

• 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&amp;lt;0.01; bootstrap 95% CI [–7.6, –1.6]) despite comparable CD4⁺ and CD8⁺ T-cell proportions at apheresis between products (p&amp;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&amp;gt;0.5). Profound immunodeficiency at Month (M) 1, defined as CD4⁺ T-cell counts &amp;lt;50/μL, was associated with a significantly shorter PFS (3.2 vs 22.4 mo, p&amp;lt;0.0001). Median CD4⁺ T-cell count recovery (&amp;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&amp;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&amp;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&amp;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.

  PublisherOA PDFDOI

Recent grants

• NIH Grant K08CA127143

  NIH · $276k · 2012

Frequent coauthors

• Jedd D. Wolchok

  110 shared

• Edward A. Stadtmauer

  University of Pennsylvania

  109 shared

• Alfred L. Garfall

  University of Pennsylvania

  96 shared

• Alan N. Houghton

  87 shared

• Noopur Raje

  Massachusetts General Hospital

  87 shared

• Dan T. Vogl

  Hospital of the University of Pennsylvania

  81 shared

• Nikhil C. Munshi

  Dana-Farber Cancer Institute

  75 shared

• Alexander M. Lesokhin

  Memorial Sloan Kettering Cancer Center

  72 shared

Labs

• Adam D Cohen LabPI

Education

• B.A.

  Harvard University

  1994

• M.D.

  University of Pennsylvania

  1999