Communicating CAR T Secondary Malignancy Risks in Hematologic Oncology

In an interview with CancerNetwork® at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting, Jasmine Zain, MD, director of the T-Cell Lymphoma Program in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope National Medical Center, discussed how oncology teams should communicate the FDA’s class-wide boxed warning on secondary T-cell malignancies following CAR T-cell therapy.

Zain initially explained that patients should be informed that the risk, while real, remains low, cited at roughly 1.5%, and that ongoing registry data collection is helping ensure emerging cases are not missed. She noted that these secondary malignancies present unpredictably, ranging from self-resolving lymphoproliferative disorders to more aggressive presentations, which complicates counseling. Finally, she emphasized that clear, detailed discussion of risks, outcomes, and screening for predisposing factors such as clonal hematopoiesis of indeterminate potential (CHIP) mutations is essential to help patients make informed decisions about pursuing cellular therapy.

Transcript:

CancerNetwork: How should multidisciplinary oncology teams communicate the risk-benefit ratio of secondary primary malignancies to patients who may express anxiety over the FDA warnings when considering cellular therapy, given that these rates are similar between CAR T-cell therapy and standard-of-care salvage regimens?

Zain: Patients should be made aware that this is a [class-wide] black box warning on the 6 approved CAR T-cell products for B-cell and multiple myeloma malignancies. The risk is higher with certain subtypes of CAR T-cell therapy, particularly BCMA-directed CAR T-cell therapies. Patients should be made aware of this, but they should also be told that the risk is very low, about 1.5%. That is what we have seen so far, and registry data are being collected to make sure we do not miss this.

The other thing to understand is that the presentations of these lymphomas are varied. They can range from a lymphoproliferative disorder or a mildly abnormal clone in the peripheral blood, which can happen with any kind of inflammatory situation, and some of these can actually resolve on their own, to presentations with skin lesions or a small collection of abnormal or malignant T cells that can easily be treated. How a patient will present if they develop this is unclear, and that is something that should be counseled to the patient as well.

It is possible that patients may refuse [cellular therapy] based on this, because sometimes these [secondary] malignancies are very difficult to treat and may result in a negative outcome. It is unpredictable, so very careful counseling of the patient is essential; making sure they do not have a CHIP mutation and understanding the underlying risk. Again, it comes down to good counseling of the patient, making sure they understand the risks and outcomes, and what can be done about these situations.

Reference

Zain JM. Understanding the risk of second malignancies after CAR T Therapies. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX.