Chidamide Plus Prednisone, Cyclophosphamide, and Thalidomide (CPCT) for Relapsed or Refractory Peripheral T-Cell Lymphoma: A Multicenter Phase II Trial

Purpose: Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of aggressive lymphomas that portends an unfavorable outcome. Although the treatment of PTCL has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory-particularly for relapsed or refractory (R/R) patients. We herein conducted a prospective, single-arm phase II clinical trial to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate standard chemotherapy for a variety of reasons.

Methods: This was an open-label, single-arm, multicenter pivotal phase II study in which patients were enrolled at 9 centers. The flow chart of the CPCT regimen: a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. The CPCT regimen was administered orally until disease progression or unacceptable toxicity as follows: chidamide at 30 mg twice weekly, prednisone at 20 mg daily after breakfast, cyclophosphamide at 50 mg daily after lunch, and thalidomide at 100 mg daily at bedtime. Our primary objective was to assess overall response rate (ORR) after treatment with CPCT, with secondary objectives to evaluate the duration of response, one-year overall survival (OS), and one-year progression-free survival (PFS).

Results: Forty-five patients were ultimately enrolled in the present study for response and safety assessments from August 2016 to April 2021 with respect to Chinese patients (the characteristics of the 45 patients with at least one treatment response assessment are listed in Figure 1A). Twenty-three patients (51.1%) were heavily pretreated before enrollment. Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% and 28.9%, respectively, and after a median follow-up period of 56 months, the median PFS and OS were 8.5 and 17.2 months, respectively (Figure 1B). The median median duration of response (DOR) was six months with a range of 0.7-71.5 months, and most responders (41 patients, 91.1%) had a DOR more than three months. Twenty-eight patients (62.2%) exhibited a DOR over six months and 17 patients (37.8%) had a DOR over 12 months. The one-year PFS and OS rates were 42.2% (95% CI, 27.7%‒56.7%) and 57.8% (95% CI, 43.3%‒72.3%), respectively, and the five-year PFS and OS rates were 21.2% (95% CI, 7.9%‒34.5%) and 43.8% (95% CI, 28.3%‒59.3%), respectively. Although subgroup survival analysis indicated no significant differences among different histopathologies (Figure 1C and D), the median PFS (p<0.001) and OS (p<0.001) were not attained for patients who achieved CR/CRu (N=13) (Figure 1E and F). The most common grade 3/4 adverse event was neutropenia (24.5%), but we observed no treatment-related mortality.

Conclusions: In conclusion, the all-oral CPCT regimen was a well-tolerated and effective treatment for R/R PTCL patients who could not tolerate standard chemotherapy for a variety of reasons. However, further studies that entail a larger sample size in different subtypes of PTCL are still required. This trial was registered in ClinicalTrials.gov (NCT02879526).

No relevant conflicts of interest to declare.