Results from a phase II trial indicate that the anti-CCR4 antibody mogamulizumab (Moga) combined with biweekly cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PSL) – a combination known as Moga-CHOP-14 – significantly improves progression-free survival (PFS) in older patients with aggressive CCR4-positive adult T-cell leukemia/lymphoma (ATL) who are ineligible for allogeneic hematopoietic cell transplantation (alloHCT). Ilseung Choi, MD, of the National Hospital Organization Kyushu Cancer Center in Japan, reported that he considers Moga-CHOP-14 to be the preferred first-line treatment for these patients. He presented the trial results June 6 at the American Society of Clinical Oncology (ASCO) Annual Meeting.
While alloHCT can improve the prognosis of younger, transplant-eligible patients with ATL, Dr. Choi noted that more than half of patients diagnosed with aggressive ATL are older than 65 to 70 years of age and ineligible for alloHCT. He and his team thus designed the phase II study to assess whether Moga-CHOP-14 is an effective treatment for treatment-naïve patients with aggressive, CCR4-positive ATL. The researchers enrolled 50 patients (48 evaluable) from November 2015 to November 2020 in 21 sites across Japan. The median follow-up for efficacy and safety analysis was 1.6 years at the data cut-off of November 30, 2021.
The trial enrolled patients age 66 years or older and those between the ages of 56 and 65 who were not candidates for alloHCT. Patients received six cycles of Moga-CHOP-14, followed by two cycles of Moga monotherapy. While the study design called for administration of a cycle every 14 days, the protocol allowed for the interval to be extended to 21 days if the patient demonstrated intolerance. Dr. Choi explained that most patients received Moga-CHOP-14 every 21 days. The relative dose intensity for each drug was 82.1% for Moga, 71.7% for CPA, 72.7% for DXR, 72.0% for VCR, and 77.3% for PSL.
The study included nine patients whose disease was considered high risk on the ATL-prognostic index , 31 considered intermediate risk, and eight considered low risk. The investigators compared patient outcome to the results of the CHOP-14 arm of the historical Jacob JCOG 9801 study. “Of note,” said Dr. Choi, “the median age of our study was 74 years compared to 58 years old in the Jacob study.”
The researchers documented a mean one-year PFS of 36.2% (90% CI 24.9-47.6) and a median PFS of 0.7 years (95% CI 0.5-1.0). The researchers observed a complete response rate of 64.6% (95% CI 49.5-77.8) and an overall response rate of 91.7% (95% CI 80.0-97.7). The one-year overall survival (OS) was 66.0% (95% CI 50.6-77.6), and the median OS was 1.6 years (95% CI 1.1-2.8). The one-year event-free survival (EFS) was 29.9% (95% CI 17.6-43.2), and the median EFS was 0.5 years (95% CI 0.4-0.7). The researchers found a 15% additional PFS effect for Moga-CHOP-14 as compared to the historical CHOP-14. The most frequent adverse events of grades 3 or 4, which occurred in 10% of patients, were lymphocytopenia (97.9%), leukopenia (93.8%), neutropenia (89.6%), febrile neutropenia (64.8%), anemia (58.3%), thrombocytopenia (45.8%), infection (27.1%), skin rash (20.8%), and hyperglycemia (20.8%).
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Choi I, Yoshimitsu M, Kusumoto S, et al. A phase 2 trial of CHOP with anti-CCR antibody mogamulizumab for elderly patients with CCR4-positive adult T-cell leukemia/lymphoma. Abstract 7504. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 6, 2023; Chicago, Illinois.