CAR T-Cell Therapy: Durable Responses Reshape Cancer Care

Chimeric antigen receptor (CAR) T-cell therapy is a reshaping treatment for several hematologic malignancies, with clinical data showing improved outcomes in aggressive lymphoma and durable responses in some patients with multiple myeloma. At the 60th Congress of the Postgraduate Education Days of the Association des Médecins anciens étudiants de l’Université libre de Bruxelles (AMUB) in 2026, Marie Vercruyssen, MD, Department of Hematology, Jules Bordet Institute, Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium, presented recent advances in therapy and discussed its emerging applications in solid tumors.Beginning in the 1970s, cancer immunotherapy gained momentum during the latter part of the 20th century, driven by a better understanding of immune checkpoint mechanisms and the introduction of monoclonal antibodies.This was followed by the development of bispecific antibodies, which can simultaneously bind two distinct targets, and, more recently, T-cell engagers, which redirect T cells toward malignant cells by linking them to specific tumor-associated antigens independently of their native T-cell receptor specificity.Lymphoma RevolutionAn equally significant innovation in hematology is CAR T-cell therapy. This approach targets cancer cells in a fundamentally different manner, essentially acting as a homing device.“The treatment involves collecting the patient’s T cells, sending them to the laboratory, modifying them so that they express antibodies on their surface capable of specifically recognizing tumor cells, multiplying these T cells, and then reinjecting them into the patient. It is a personalized, tailor-made treatment because the patient’s own T cells are engineered to express the characteristics needed to recognize their tumor,” said Vercruyssen.“Since R-CHOP [rituximab + cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine (Oncovin), prednisone] — that is, since the rituximab revolution — we hadn’t made much progress in treating diffuse large B-cell lymphoma, the most common hematological condition in adult patients. We’ve achieved a 5% increase in median progression-free survival. That’s not exactly remarkable,” Vercruyssen said.For patients whose disease is refractory to initial treatment or relapses within 12 months, the introduction of axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy, alters the treatment landscape.“There’s no contest. We’re seeing a 30% survival rate with standard care compared with 50% with axi-cel. This therapy has completely revolutionized our approach to treatment, which is why axi-cel is now covered as a second-line treatment for patients who relapse early, that is, within 1 year, or whose disease is refractory.”Multiple MyelomaThe results are similar in multiple myeloma, according to the CARTITUDE-1 study, which evaluated the safety and clinical efficacy of ciltacabtagene autoleucel (cilta-cel), another CAR T-cell therapy.“The patients enrolled had received an average of six lines of treatment, which in the case of multiple myeloma indicates a very poor prognosis. Yet, nearly all of them responded to treatment, which is extraordinary in and of itself. Most patients also achieved a complete response, or even a very good partial response and excellent partial remission.“What was particularly notable was that, in this study, median progression-free survival was 3 years. We’re no longer talking about overall survival,” said Vercruyssen.Long-term results from the study are now also available. In the hematologist’s own words, they were “simply mind-blowing.”“We’re seeing a plateau in progression-free survival and overall survival. This is unprecedented for multiple myeloma. In this specific population, it is possible to cure the disease. It is also a paradigm shift. We’re no longer talking about long-term treatment, but rather a lifelong therapy whose effects persist,” she said.Side EffectsThese results are striking, but what are the side effects?“There is clearly a new profile of side effects, different from those seen with chemotherapy. These can be inflammatory, neurologic, hematologic, and infectious, particularly involving the John Cunningham virus and reactivation of a number of other viruses.”“Most of the treatment takes place in the hospital,” Vercruyssen said. She cited examples of peripheral facial paralysis and delayed neutropenia, with the latter potentially persisting for more than 100 days after infusion. She emphasized the importance of long-term follow-up and close collaboration between hematology departments and primary care physicians.“You are the ones who see these patients next during their follow-up visits.”Solid TumorsHematology may not be the only field that benefits from advances in CAR T-cell therapy.“Several studies are currently underway on glioblastoma and are showing encouraging and exciting results. In particular, some studies have evaluated the repeated intrathecal administration of CAR T cells. However, solid tumors remain more difficult to treat because of their large tumor mass and the immunosuppressive microenvironment surrounding them. Studies are being conducted in Rome, and others may soon be launched in Belgium.”The Jules Bordet Institute, part of the HUB, has acquired equipment that will enable it to conduct its own procedures and academic studies. A commissioning and training period of approximately 6 months will be required.“Glioblastoma is among the first indications we hope to study,” Vercruyssen said.This story was translated from MediQuality, part of the Medscape Professional Network.