CHOP VERSUS GEM‐P IN THE FIRST‐LINE TREATMENT OF T‐CELL LYMPHOMA (PTCL): INITIAL RESULTS OF THE UK NRCI PHASE II RANDOMISED CHEMO‐T TRIAL

Abstract

Introduction: Outcomes with CHOP in the first-line treatment of PTCL are poor and a superior regimen is required. Gemcitabine is not effluxed by the multidrug resistance gene-1/P glycoprotein (expressed in ~60% of PTCLs) and has demonstrated efficacy in relapsed/refractory PTCL both as a single agent and in combination. Method(s): We conducted a phase II multicenter randomised trial for previously untreated patients >=18 years with bulky stage I- IV PTCL of the following subtypes: PTCL not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) ALK negative, enteropathy-associated T-cell lymphoma (EATL), and hepatosplenic gamma delta T-cell lymphoma. The trial was funded by Bloodwise. Patients were randomised (stratified by subtype and IPI) to receive either 6 cycles of intravenous (IV) cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 on D1 and oral (PO) prednisolone 100 mg once daily (OD) D1-5 (CHOP) every 21 days (Arm A) or 4 cycles of gemcitabine 1000 mg/m2 IV D 1, 8 and 15, cisplatin 100 mg/m2 IV on D15 and methylprednisolone 1000 mg (IV/PO) OD on D1-5 (GEM-P) every 28 days (Arm B). The primary endpoint was a comparison of end of treatment (EOT) complete response (CR)/CR unconfirmed (CRu) rates assessed by CT using IWG 1999 criteria. The CR/CRu rate was expected to be 50% in Arm A and increased to 70% in Arm B; 93 patients were required per arm to detect this difference with 80% power and 2-sided alpha of 5%. Result(s): From March 2012 to November 2016, 87 patients were accrued from 47 sites (U.K. n = 46, Australia n = 1). The trial profile is shown in Figure 1. On 22.11.2016 the independent data monitoring committee recommended the trial should close early as the primary endpoint would not be met. Baseline characteristics are shown in (Figure Presented) Table 1. EOT response is currently evaluable for n = 72, CR/CRu Arm A = 57.1% and Arm B = 43.2% (p = 0.24). Overall rates of grade >= 3 toxicity were similar between arms, 67.0% vs 73.0% (p = 0.64); however (Table Presented) more >=3 grade neutropenia (p = 0.036) and febrile neutropenia (p = 0.03) were seen in Arm A; while Arm B had more >=3 grade thrombocytopenia (p = 0.03). At a median follow-up of 18.1 months, there was no difference in 2-yr overall survival (Arm A = 53.1%, Arm B = 64.7%, p = 0.56) or progression-free survival (Arm A = 36.0%, Arm B = 39.0%, p = 0.81). Conclusion(s): The EOT CR/CRu rate in Arm B (GEM-P) was not superior to Arm A (CHOP), and Arm B was associated with higher rates of study withdrawal. CHOP remains the reference regimen in PTCL.