The Addition of Romidepsin to CHOEP and High-Dose Chemotherapy Plus Stem Cell Transplantation Did Not Ameliorate the Outcome of Untreated Angioimmunoblastic T-Cell or Follicular T-Helper Lymphoma: Subgroup Analysis of Phase II FIL-PTCL13 Study

Abstract

Introduction: In the phase Ib/II study PTCL13 study (NCT02223208) we demonstrated feasibility of Romidepsin 14 mg/mq in addition to CHOEP followed by high-dose chemotherapy and stem cell transplantation (SCT), but no benefit was observed in term of progression free survival (PFS), and the enrollment of the trial was stopped due to inefficacy of the experimental combination. Other studies showed Romidepsin activity in relapsed or refractory PTCLs, especially in angioimmunoblastic (AITL) subtype, expecially when combined with azacytidine. On this basis, we conducted a sub-analysis of the PTCL13 trial, with the aim to evaluate the role of adding Romidepsin to CHOEP followed by high dose chemotherapy and SCT in newly diagnosis AITL and T-helper follicular lymphoma patients. Methods: Patients aged 18-65 eligible to SCT, with advanced PTCL-NOS, AITL/T-helper follicular and ALK negative anaplastic large cell lymphoma, were eligible to PTCL13 study. Treatment plan consisted of 6 courses of Ro-CHOEP every 21 days (14 mg/ms Ro day 1 and 8), followed by cisplatin-cytarabine-dexamethasone (DHAP) with stem cell harvest and SCT. Patients in complete response (CR) after induction proceeded to autoSCT, while those in partial response (PR), with an available HLA-matched donor, proceeded to alloSCT upfront. Results: 89 patients were enrolled into the phase Ib and II part of the study; median age was 55 years (IQR 49;60); 78 (91%) had stage III-IV and 31 (36%) IPI risk >2. Pathological materials were collected at the time of diagnosis, and centrally reviewed by expert hemo-pathologist; subgroups were: 34 PTCL-NOS, 21 ALK negative and 31 AITL/THF. The clinical characteristics of the 31 AITL/THF patients were: median age 56 years (IQR 52.5-59.5), 63% male, 31% had an intermediate-high IPI score risk and 50% had a bone marrow involvement at diagnosis. The overall response (ORR) at the end of induction with 6 Romidepsin-CHOEP was achieved in 7 AITL/THF patients (22%), with 6 (19%) patients in complete remission (CR); at the end of treatment, the ORR was observed in 15 (47%) AITL/THF patients. ORR and CR results are superimposable to those of the whole population. At a median follow-up of 28 months, the 24-months PFS for AITL/THF was 43% (95% CI: 0.22-0.61) compared to 24-months PFS for ALK-negative 37% (95% CI: 0.16-0.59) and for PTCL-nos 33% (95% CI: 0.18-0.48), p 0.136; the 24-months OS for AITL/THF was 78% (95% CI: 0.57-0.89) compared to 24-months OS for ALK-negative 63% (95% CI: 0.37-0.81) and for PTCL-nos 61% (95% CI: 0.40-0.76), p 0.556. Conclusions: In the FIL-PTCL13 the primary endpoint was not met and the enrollment of the trial was stopped due to inefficacy of the experimental combination. With the limits of the small number and the unpowered analysis, the benefit of adding romidepsin to chemotherapy was not observed in the subgroup AITL/THF patients, even if the PFS and the OS of this subgroup seem better than the others.