Researchers have successfully employed a CCR4-directed strategy to achieve durable responses in patients with T-cell lymphoma following treatment with anti-BCMA CAR T-cell therapy. While CAR T-cell therapy has shown significant efficacy in treating hematologic malignancies, concerns over rare secondary malignancies have emerged. A recent case highlighted the potential for innovative treatment approaches to manage these complications effectively.
In an interview with OncLive®, study investigator Samir Parekh, MD, discussed the circumstances surrounding a patient who developed a secondary malignancy after receiving anti-BCMA CAR T-cell therapy. This patient, a 50-year-old man with relapsed multiple myeloma, initially entered remission following treatment. Despite mild complications such as cytokine release syndrome and viral infections, he later presented with a facial rash that was diagnosed as T-cell lymphoma.
Challenges of Secondary Malignancies
The diagnosis of secondary malignancies following CAR T-cell therapy, although rare, poses significant challenges for physicians. According to Parekh, studies have shown an incidence of 5% to 6% for these adverse effects, with only a handful of patients reported with T-cell lymphomas after anti-BCMA CAR T-cell therapy. The FDA issued a warning in early 2024 urging healthcare professionals to monitor for such occurrences.
As the patient’s condition deteriorated, with signs of lymphoma spreading aggressively in the blood and lymph nodes, Parekh and his team sought a tailored treatment plan. They collaborated with experts in dermatology and immunology to explore various FDA-approved therapies that would target the lymphoma cells while minimizing harm to the patient’s immune system, which was already compromised due to the previous CAR T-cell therapy.
Innovative Treatment Approach
The collaborative effort led to the identification of CCR4 as a promising target. This surface marker is associated with certain T-cell lymphomas, and an existing monoclonal antibody, mogamulizumab (Poteligeo), had previously been approved for different indications, primarily in HTLV-associated adult T-cell lymphoma. By repurposing this drug and combining it with other effective agents, the medical team crafted a comprehensive treatment strategy.
Using a combination of mogamulizumab, an anthracycline, and gemcitabine—commonly used in lymphoma treatment—the team observed remarkable results. Within days, the patient’s skin lesions and lymph node involvement began to resolve. After one or two cycles of treatment, he achieved complete remission and has remained disease-free for over a year and a half.
The patient recently shared that he enjoyed a family vacation at Yosemite National Park, reflecting a significant improvement in his quality of life.
This case underscores the importance of precision medicine and the potential for drug repurposing in addressing rare complications following CAR T-cell therapy. As more patients receive these advanced treatments, continued vigilance and innovative approaches will be crucial in managing outcomes effectively.
