Systematic Review of Secondary Primary Malignancies (SPMs) in Patients Treated with Chimeric Antigen Receptor T-cell (CAR-T) Therapies
Author(s)
Mounzer E. Agha, MD1, Sarah McGregor, PA-C2, Kevin C De Braganca, MD3, Tamar Lengil, PhD4, Victoria Alegria, MS5, Denise De Wiest, MD6, Matthew Perciavalle, PharmD7, Ravi Potluri, MBA8, Sandip Ranjan, MTech9, Ahmed Mohamed, MD, PhD10, Helen Pai, MS11, Todd Bixby, RPh, MBA5, Zaina P. Qureshi, MPH, MS, PhD5, Peter M. Voorhees, MD12;
1UPMC Hillman Cancer Center, Pittsburgh, PA, USA, 2Hillman Cancer Center, Pittsburgh, PA, USA, 3Janssen Research & Development, Horsham, PA, USA, 4Johnson & Johnson, Raritan, NJ, USA, 5Janssen Scientific Affairs, LLC, Horsham, PA, USA, 6The Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, USA, 7Legend Biotech USA, Inc, Somerset, NJ, USA, 8Putnam Associates, New York, NY, USA, 9Putnam Associates, Gurugram, India, 10The Janssen Pharmaceutical Companies of Johnson & Johnson, Germantown, MD, USA, 11Janssen Research & Development, LLC, Raritan, NJ, USA, 12Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC, USA
1UPMC Hillman Cancer Center, Pittsburgh, PA, USA, 2Hillman Cancer Center, Pittsburgh, PA, USA, 3Janssen Research & Development, Horsham, PA, USA, 4Johnson & Johnson, Raritan, NJ, USA, 5Janssen Scientific Affairs, LLC, Horsham, PA, USA, 6The Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, USA, 7Legend Biotech USA, Inc, Somerset, NJ, USA, 8Putnam Associates, New York, NY, USA, 9Putnam Associates, Gurugram, India, 10The Janssen Pharmaceutical Companies of Johnson & Johnson, Germantown, MD, USA, 11Janssen Research & Development, LLC, Raritan, NJ, USA, 12Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC, USA
Presentation Documents
OBJECTIVES: CAR-T therapies have demonstrated transformative efficacy in inducing durable remissions in approved indications. However, eligible patients are often heavily pretreated, putting them at risk of developing SPMs. We aimed to catalogue SPM occurrence in CAR-T treated patients, and if SPMs were ascribed to the CAR-T therapy.
METHODS: A systematic literature review was conducted through October 1, 2024 to identify evidence on SPMs with CAR-T therapies in approved indications. No restrictions were applied on study type/geography. Retrieved records were screened against pre-defined PICOS criteria.
RESULTS: 114 unique relevant publications were identified. Fifty studies involved lymphomas, 18 involved multiple myeloma, 12 involved leukemias, and 8 a mix of these. Rates of SPMs ranged from 0.0-30.8% of those treated with CAR-T therapy (median 4.3%). Number of SPMs per affected patient ranged from 1.0-1.7 (median 1.0). Not counting studies reporting only myeloid SPMs, hematologic SPMs accounted for a median of 50% of SPMs across indications. Of 56 studies that reported T-cell malignancies, 8 reported 18 cases in total. In 4 randomized trials, SPM rates were comparable between CAR-T and comparator arms, although heme SPMs were numerically greater [1.8% vs 0.0% (ZUMA-7), 2.2% vs 0.0% (KarMMA-3), 3.4% vs 0.5% (CARTITUDE-4), not reported (TRANSFORM)]. Deaths due to SPMs accounted for 0.2-4.8% of CAR-T treated patients (median: 1.7%) in 38 studies. In 353 of 356 cases, other confounding factors were identified as potential causes of SPMs such as advanced age, smoking history or genetic factors, or causation was not established, with the other 3 cases attributed to CAR-T therapy.
CONCLUSIONS: In RCTs, CAR-T therapies were not seen to result in increased risk of overall SPMs, and the rates of hematologic SPMs, while low, were numerically higher in the CAR-T arms. T-cell malignancies have been uncommonly reported. Attribution of SPMs to CAR-T cell therapy can be confounded by other risk factors.
METHODS: A systematic literature review was conducted through October 1, 2024 to identify evidence on SPMs with CAR-T therapies in approved indications. No restrictions were applied on study type/geography. Retrieved records were screened against pre-defined PICOS criteria.
RESULTS: 114 unique relevant publications were identified. Fifty studies involved lymphomas, 18 involved multiple myeloma, 12 involved leukemias, and 8 a mix of these. Rates of SPMs ranged from 0.0-30.8% of those treated with CAR-T therapy (median 4.3%). Number of SPMs per affected patient ranged from 1.0-1.7 (median 1.0). Not counting studies reporting only myeloid SPMs, hematologic SPMs accounted for a median of 50% of SPMs across indications. Of 56 studies that reported T-cell malignancies, 8 reported 18 cases in total. In 4 randomized trials, SPM rates were comparable between CAR-T and comparator arms, although heme SPMs were numerically greater [1.8% vs 0.0% (ZUMA-7), 2.2% vs 0.0% (KarMMA-3), 3.4% vs 0.5% (CARTITUDE-4), not reported (TRANSFORM)]. Deaths due to SPMs accounted for 0.2-4.8% of CAR-T treated patients (median: 1.7%) in 38 studies. In 353 of 356 cases, other confounding factors were identified as potential causes of SPMs such as advanced age, smoking history or genetic factors, or causation was not established, with the other 3 cases attributed to CAR-T therapy.
CONCLUSIONS: In RCTs, CAR-T therapies were not seen to result in increased risk of overall SPMs, and the rates of hematologic SPMs, while low, were numerically higher in the CAR-T arms. T-cell malignancies have been uncommonly reported. Attribution of SPMs to CAR-T cell therapy can be confounded by other risk factors.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO45
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
SDC: Oncology