|The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
The addition of azacitidine to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) demonstrated promising antitumor activity among patients with previously untreated peripheral T-cell lymphoma (PTCL), particularly in the T-follicular helper cell phenotype (TFH) of angioimmunoblastic T-cell lymphoma (AITL), according to results of a phase 2 trial presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“We hypothesized that chemo-sensitization using epigenetic priming with CC486 in combination with chemotherapy can lead to improved response and outcome,” Jia Ruan, MD, PhD, of the Weill Cornell Medicine and New York Presbyterian Hospital in NYC, and presenter of the study, said.
AITL is associated with mutations that affect epigenetic regulators; therefore, a hypomethylating agent such as azacitidine may have clinical activity. Azacitidine monotherapy was shown to have antitumor activity in relapsed/refractory PTCL in a previous study. The purpose of this study was to evaluate it in combination with CHOP in a PTCL population enriched for AITL.
The phase 2 study treated 21 patients with previously untreated PTCL with azacitidine plus CHOP. All patients also received granulocyte-colony stimulating factor (G-CSF). The primary endpoint was complete response (CR), and secondary endpoints included objective response rate (ORR), survival, and safety.
The median patient age at baseline was 66 years, and 62% of patients were male. Most patients had stage III/IV disease at 90%, 48% had elevated lactate dehydrogenase, 33% had bone marrow involvement, and 43% had an International Prognostic Score of 3 to 5. The PTCL subtypes included 81% that were TFH, 14% that were not otherwise specified, and 5% that were adult T-cell leukemia.
The ORR was 85% after 3 cycles; this included a 55% CR rate. By the end of treatment, which was 6 cycles, the CR rate increased to 75% for the entire cohort, and was 88% among patients with PTCL-TFH.
During a median follow-up of 15 months, the 1-year PFS was 66.1% and 1-year OS was 80.7%. Among patients with PTCL-TFH, the 1-year PFS and OS were 69.9% and 93.8%, respectively.
Achieving CR was not associated with CD30 expression.
“Although preliminary, recurrent [mutation] of epigenetic modulators appears to have an impact on response and survival,” Dr Ruan said. TET2 mutations were significantly associated with better PFS (P =.0039), whereas DNMT3A mutations were associated with poor OS (P =.0192).
The most common grade 3 to 4 adverse events (AEs) were neutropenia, anemia, fatigue, and hyponatremia.
Dr Ruan concluded that “the addition of this oral hypomethylating agent to CHOP as initial therapy for PTCL is safe, well tolerated, and induces high response rates.”
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.
Ruan J, Moskowitz AJ, Mehta-Shah N, et al. Multi-center phase II study of oral azacitidine (CC-486) plus CHOP as initial treatment for peripheral T-cell lymphoma (PTCL). Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 40.