Professor of Clinical Medicine, Sandra and Edward Fellow, lead study author Dr. “The treatment shows promise for this subtype of T-cell lymphoma, and we look forward to seeing how it performs in a larger clinical trial,” Jia Ruan said. Meyer Cancer Center at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The study involved many researchers at Weill Cornell Medicine, including Drs. Peter Martin, John Leonard, Leandro Cerchietti, Giorgio Inghirami, Olivier Elemento and Ari Melnick. Investigators from Memorial Sloan Kettering, Washington University School of Medicine, Moffitt Cancer Center, and BostonGene Corporation also contributed to the study.
Non-Hodgkin’s Lymphoma Clinical Trial Results
Lymphomas arise from immune cells, mainly B cells and T cells, whose malignant growth causes swollen lymph nodes. About 90,000 people in the United States are newly diagnosed with these cancers each year. PTCLs, which account for several thousand of these cases, are relatively difficult to treat successfully, with an estimated five-year survival rate of only 20 to 30 percent.
The standard initial therapy for most lymphomas is a four-drug chemotherapy regimen (CHOP), usually given in six three-week cycles. Researchers are looking for ways to improve the effectiveness of this treatment for PTCL and other forms of lymphoma that tend to have poor outcomes.
Combining standard chemotherapy with azacitidine is a promising strategy and is currently being tested in various settings. Dr. A small study led by Martin and published last year found that combination therapy was effective in producing complete response rates in patients with certain aggressive B-cell lymphomas.
Azacitidine, currently approved by the US Food and Drug Administration for the treatment of myelodysplastic syndrome and some leukemias, works to reverse gene regulatory imprints in DNA called methylation. Many aggressive cancers harbor dense patches—hypermethylations—of these DNA marks, which are thought to increase tumor survival by silencing growth-restricting and DNA-repairing genes. In a new study, Dr. Ruan and his colleagues investigated the efficacy of the combination in PTCL patients with the TFH subtype, because PTCL-TFH tumors typically show signs of excessive DNA methylation as well as mutations in one or more methylation-regulating genes. v The study included 20 evaluable PTCL patients, 17 of whom had the TFH subtype based on genetic testing of their tumors. All but one had advanced PTCL of stages III-IV. The rate of complete responses at the end of azacitidine-plus-standard chemotherapy treatment was very high: three-quarters (15/20) of patients had a complete response and all were PTCL-TFH patients—implying a complete response rate. 88.2 percent for this subgroup. Complete response rates at the end of treatment for PTCL patients treated only with standard chemotherapy, such as CHOP-based regimens, are typically in the 30 to 40 percent range, Dr. Rouen.
Median follow-up for the patients was 21 months, allowing the researchers to estimate two-year progression-free survival rates of 65.8 percent for all 20 patients and 69.2 percent for the 17 PTCL-TFH patients. Side effects are usually comparable to those seen with standard chemotherapy treatment. The researchers are now working with colleagues across the country examining azacitidine-plus-standard chemotherapy in a randomized clinical trial in a cohort of more than 150 PTCL patients of various subtypes, scheduled to be completed by 2026.