Resistance to routine immunochemotherapy remains an unmet need in diffuse large B-cell lymphoma (DLBCL), and abnormal DNA methylation may play a role in chemoresistance. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with subcutaneous azacitidine, a hypomethylating drug, yielded promising early-phase outcomes. For a study, researchers assessed CC-486 (oral azacitidine) plus 6 cycles of R-CHOP in patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma in the phase 1 trial. 

CC-486 dosages of 100, 150, 200, or 300 mg were administered 7 days before cycle 1, and on days 8-21 of cycles 1-5; additional patients were added in the expansion phase to assess preliminary effectiveness. The major goals were to assess the safety and MTD of CC-486 in conjunction with R-CHOP. 

The most prevalent grade 3/4 toxicities were hematologic, including neutropenia (62.7%) and febrile neutropenia (25.4%); grade 3/4 non-hematologic toxicities were uncommon (7%). The MTD was not determined; nevertheless, 2 patients experienced dose-limiting toxicity (1 with grade 4 febrile neutropenia; 1 with grade 4 prolonged neutropenia). Therefore, the 300 mg dosage was the recommended phase 2 dose. The overall response rate was 94.9%, with 52 patients (88.1%) completing the survey. The projected 1- and 2-year progression-free survival rates were 84.1 and 78.6%, respectively, with a median follow-up of 28.9 months. 

Patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma could benefit from epigenetic priming with CC-486 before R-CHOP with tolerable safety.

Source:ashpublications.org/blood/article-abstract/139/8/1147/476663/Phase-1-study-of-oral-azacitidine-CC-486-plus-R?redirectedFrom=fulltext