CAR T-Cell Therapies Show Promise in Myeloma and AML; Case Report Flags Rare Complication
New CAR T-cell data show 100% MRD negativity in high-risk smoldering multiple myeloma, a novel CAR T approach for AML, and a new T-cell pathway, while a case report warns of a rare therapy-related complication.
Recent findings highlight both the promise and the risks of CAR T-cell therapy in blood cancers, with new studies showing high measurable residual disease (MRD)-negativity rates in multiple myeloma and a novel CAR T approach for acute myeloid leukemia (AML), while a case report underscores a rare complication.
A single infusion of the CAR T-cell therapy ciltacabtagene autoleucel led to a 100% MRD-negativity rate in patients with high-risk smoldering multiple myeloma, according to results from CAR-PRISM, a phase II clinical trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2026. Within 2 months of treatment, all 20 patients achieved MRD negativity, which was sustained at a median follow-up of 15.3 months. Six patients followed for longer than 18 months continued to experience MRD negativity, and no disease progression or deaths were observed during follow-up.
All patients treated with ciltacabtagene autoleucel experienced low-grade cytokine-release syndrome, with no grade 3 or higher events. The most common adverse events were transient hematologic toxicities, including grade 3 or 4 neutropenia. Non-ICANS neurologic toxicities occurred in seven patients: facial nerve palsy in four patients that resolved completely, and residual—but improved—mild motor symptoms in three patients. In November 2025, the U.S. Food and Drug Administration approved daratumumab and hyaluronidase for the treatment of high-risk smoldering multiple myeloma, the first approved therapy for the condition, but that trial did not evaluate MRD.
In AML, researchers at Memorial Sloan Kettering Cancer Center have developed a new type of CAR T cell therapy that targets U5 snRNP200, a protein found almost exclusively on leukemia cells and not on healthy cells, appearing on the surface of leukemia cells in about half of all AML patients. The team used antibodies discovered in AML patients whose cancer went into long-term remission following a bone marrow transplant, engineering them into CAR T cells. In mouse models, the engineered cells eliminated leukemia in both adult and pediatric AML, as well as B-cell acute lymphoblastic leukemia and pediatric leukemia, and provided long-lasting protection. To make the therapy more effective, the researchers "armored" the CAR T cells by genetically modifying them to continuously secrete interleukin-18, which increases the amount of target protein on cancer cells and supports the immune system. The findings were published in Cancer Discovery.
Separately, researchers at The University of Texas MD Anderson Cancer Center identified a previously unknown way in which T cells attack AML cells, even when the cancer cells evade conventional immune recognition. The study, published in Proceedings of the National Academy of Sciences, showed that the process depends on the CD64 protein and an intact T cell receptor, but does not require the usual MHC molecules that normally guide T cells. Removing CD64 made AML cells resistant to T cells, while adding CD64 into normally resistant AML cells made them more susceptible. The findings may help explain why AML is particularly sensitive to immune-based therapies and could inform future therapeutic strategies.
In multiple myeloma, an expert panel concluded that bridging therapy before anti-BCMA CAR T-cell therapy should be considered for further debulking as needed. The consensus, published in Bone Marrow Transplantation, said "Yes" to considering extension of bridging therapy based on its importance to CAR T outcomes.
A case report describes a patient with stage III non-germinal center diffuse large B-cell lymphoma who underwent CAR-T therapy following chemotherapy and subsequently developed treatment-related myelodysplastic syndrome that rapidly progressed to acute myeloid leukemia within two months. The authors emphasize that persistent post-CAR-T cytopenia may represent an early manifestation of an underlying therapy-related myeloid neoplasm rather than transient hematotoxicity, highlighting the need for prompt diagnosis and clinical attention.