A team of researchers from The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai has successfully treated a rare and aggressive T-cell lymphoma that developed after CAR T-cell therapy for multiple myeloma , marking a first in the field of hematologic cancer research. The findings were published in the August 21 issue of the New England Journal of Medicine .
CAR T therapy, which reprograms a patient's immune cells to attack cancer, has shown transformative results in treating multiple myeloma. However, in rare cases, serious complications such as secondary cancers can occur. In this groundbreaking case, a 51-year-old patient went into complete remission from myeloma following B-cell maturation antigen CAR T treatment but subsequently developed rapidly progressing T cell lymphoma in his skin, blood, and bone marrow.
Using advanced genetic and immunologic screening techniques developed at Mount Sinai, the research team identified a combination of compounds approved by the Food and Drug Administration that were capable of targeting the lymphoma. Notably, they discovered that the antibody drug anti-CCR4 (never before used in this context) was effective in eliminating the patient's cancer. Today, the patient remains in remission from both multiple myeloma and lymphoma.
"This is the first reported case of successfully using targeted therapy to treat a CAR positive T-cell lymphoma," said senior author Samir Parekh, MD, Director of the Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "It highlights the importance of monitoring for secondary cancers and leveraging precision medicine to respond quickly when they emerge."
Mount Sinai researchers are continuing to investigate the biology of these rare side effects and developing safer and more durable CAR T treatments for patients with multiple myeloma.
This research represents a multidisciplinary collaboration between the labs of Joshua Brody, MD , Patrick Brunner, MD, MSc and The Parekh Lab , the Icahn Genomics Institute, and the Departments of Pathology, Molecular and Cell-Based Medicine, and Immunology and Immunotherapy, at the Icahn School of Medicine at Mount Sinai in New York. Lead authors Adolfo Aleman, PhD, and Oliver Van Oekelen, MD, PhD, contributed equally to the study. The team also included David T. Melnekoff, PhD (deceased); Leah Grossman, MS; Tarek H. Mouhieddine, MD; Agata Kurowski, PhD; Ivan Odak, PhD; Sidorela Reci, BA; Shriya Desai, BA; Shannon Meledathu, BS; Malini P. Naidu, BA; Ravi P. Shukla, PhD; Rudra P. Dutta, PhD; Katerina Kappes, BS; Kseniya Serebryakova, LPN; Hayley Jackson, BA; Jordan Lu, BA; Anastasia Chatikhine; Raksha Kulkarni, MD; Zahra Moinfar, MD, PhD; Matthew M. Croken, PhD; Meenakshi Mehrotra, PhD; Brett Baskovich, MD; Sampanna Rayamajhi, MD; Shambavi Richard, MD; Adriana C. Rossi, MD; Christian Salib, MD; Jane Houldsworth, PhD; Brian D. Brown, PhD; Miriam Merad, MD, PhD; Alessandro Laganà, PhD; Patrick M. Brunner, MD, MSc; Sundar Jagannath, MBBS; Joshua D. Brody, MD; and Dr. Parekh.
Funding was provided from the National Institutes of Health, the Leukemia & Lymphoma Society, and philanthropic contributions dedicated to advancing research in multiple myeloma.
