Ruan et al administered oral azacitidine (CC-486) prior to each cycle of cytotoxic CHOP therapy in PTCL. CHOP chemotherapy doses did not require modification for any participant.Īzacitidine at low doses serves as an epigenetic modifier by regulating DNA methylation, whereas at higher doses it can be directly cytotoxic. The regimen was largely well tolerated, with the most common side effects hematological and no treatment-related deaths. Notably, some participants experienced clinical responses to oral Aza alone however, no responses were seen in the non-nTFHL participants. This translated into an estimated 2-year progression-free survival (PFS) and overall survival (OS) of 65.8% and 68.4% for all-comers, and a 2-year PFS and OS of 69.2% and 76.1%, respectively, for nTFHL. The overall response rate (ORR) and CR rate for the nTFHL subset was higher at 88% than for the entire group. Of the evaluable 20 participants, 75% achieved a response to Aza-CHOP, all complete responses (CRs). This single-arm phase 2 study included 21 adult participants, of which 81% (n = 17) had nTFHL. Ruan et al investigated the role of epigenetic priming with the oral DNA methyltransferase inhibitor azacitidine (Aza) administered prior to each cycle of CHOP chemotherapy (Aza-CHOP). Abnormalities in epigenetic modifiers have been identified in several PTCL subtypes, particularly those derived from T follicular helper (TFH) cells, and therapies targeting the epigenome can result in durable responses. 4 This highlights the need for integrating novel agents into treatment strategies. 2 Attempts at intensification of cytotoxic regimens have largely been unsuccessful in improving survival, with the possible exception of adding etoposide to initial therapy and consolidation in first remission with high-dose chemotherapy followed by stem cell rescue, although the benefits of these strategies may be limited to select PTCL subtypes. However, outcomes in PTCL if treated with the same regimes are significantly worse compared with matched patients with aggressive B-cell lymphomas, 3 and cytotoxic chemotherapy is rarely curative. 2 The current upfront approach in PTCL of using anthracycline-containing regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is largely based on extrapolation from studies in aggressive lymphomas that included few participants with PTCL. Unfortunately, PTCLs generally have disappointing response rates and short durations of response to cytotoxic chemotherapy. PTCLs are a group of heterogeneous lymphomas.
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