The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

Abstract

Objective: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). Methods: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS). Results: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. Conclusions: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Chidamide combined with cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with peripheral T-cell lymphoma

“…The ORR was 89% (16/18), with a CR of 72%. Chidamide was combined with CHOEP (CHOP with etoposide) in a phase 1b/2 study ( 32 ). The RP2D for chidamide was determined to be 20 mg twice a week for 3 weeks.…”

Therapeutic potential of tucidinostat, a subtype-selective HDAC inhibitor, in cancer treatment

“…The Chi-CHOEP regimen was well tolerated, and the observed adverse events were manageable. The results showed that the overall response rate was 60.2% (68/113), with a complete response rate of 40.7% (46/113) (Zhang et al, 2021). In order to compare the efficacy of chemotherapy plus Frontiers in Pharmacology frontiersin.org tucidinostat vs. chemotherapy for patients with newly diagnosed PTCL, a study was carried out and data showed patients in chemotherapy plus tucidinostat group had superior progressionfree survival (PFS) (p = 0.047).…”

Chidamide as monotherapy and in combination with traditional chemotherapy in peripheral T-cell lymphoma：a systematic review and meta-analysis

“…Quality assessments for individual studies using a modi ed Downs and Black checklist are provided in the Table 2. Frontiers in Immunology g 22 [10] Newlydiagnosed Phase 2 NCT03273452 chidamide +prednisone,+etoposide+thalidomide 68 49(72%) 63(25-83) American Journal of Hematology g 21 [11] Newlydiagnosed Phase 2)and 65.8%(95% CI, 54.4-75.6%, Figure 2), respectively;the CR rates and ORR rate of 7 trials were highly heterogeneous (Q=74.026, I 2 = 90.544%,, P=0.000, Figure 2A Q=65.065, I 2 = 89.242%,, P=0.000, Figure 2B).…”