Researchers have found that azacitidine may be capable of increasing the effectiveness of chemotherapy and aiding nearly 90% of patients who had peripheral T-cell lymphoma with the T follicular helper cell phenotype (PTCL-TFH) achieve remission, according to a novel study published by Ruan et al in Blood.
Background
Lymphomas arise from immune cells, mostly B cells and T cells, whose malignant overgrowth leads to the swelling of lymph nodes. These cancers are newly diagnosed in approximately 90,000 patients in the United States per year. PTCLs, accounting for several thousand cases of lymphoma per year, are relatively hard to treat successfully, and are associated with an estimated 5-year survival rate of 20% to 30%.
A standard four-drug chemotherapy regimen of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) is often given in six 3-week cycles as neoadjuvant therapy. Researchers have been looking for ways to enhance the effectiveness of this treatment for patients with PTCL and other forms of lymphoma that tend to have poor outcomes.
Patients with PTCL-TFH—an aggressive subtype of non-Hodgkin lymphoma—have tumors that typically bear excessive clusters of DNA methylation as well as mutations in one or more methylation-regulating genes. Further, many aggressive cancer types harbor dense patches of DNA hypermethylation—which are thought to enhance tumor survival by silencing growth-restraining and DNA-repair genes.
Azacitidine, which is currently approved by the U.S. Food and Drug Administration for the treatment of patients with myelodysplastic syndrome and some leukemias, works to remove these DNA methylations.
Study Methods
In the new phase II trial, the researchers assigned 3 patients who had PTCL but no TFH subtype and 17 patients who had PTCL-TFH—all but one of whom had stage III or stage IV cancer—to receive azacitidine in combination with the CHOP chemotherapy regimen.
After a median follow-up of 21 months, the researchers discovered that the patients who had PTCL-TFH demonstrated a complete response rate of 88.2%. Although there was no placebo or standard-treatment comparison group, they emphasized that end-of-treatment complete response rates for patients with PTCL treated with only standard CHOP-based chemotherapy regimens are usually 30% to 40%.
The researchers estimated that the 17 patients with PTCL-TFH and all 20 patients involved in the trial would experience 2-year progression-free survival rates of 69.2% and 65.8%, respectively. Side effects were comparable to what is normally observed in standard chemotherapy treatment.
The researchers highlighted that previous studies have found that azacitidine in combination with chemotherapy was effective at producing complete response rates in patients with certain aggressive B-cell lymphomas.
Conclusions
“The treatment shows promise for this T-cell lymphoma subtype, and we look forward to seeing how it performs in a larger clinical trial,” noted lead study author Jia Ruan, MD, PhD, Professor of Clinical Medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
Because all of the patients who showed a complete response to therapy had the TFH subtype, the researchers implied that the new findings were consistent with the idea that combining azacitidine with standard chemotherapy may be a promising and safe strategy for this patient population.
The researchers are currently investigating the efficacy of the combination therapy in a randomized clinical trial involving over 150 patients with PTCL of different subtypes. The study is expected to be completed by 2026.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
