A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T‐cell lymphoma (PTCL): final results from the T‐ cell consortium trial

Abstract

Summary Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP-P) in PTCL. Patients achieving a complete or partial remission (CR/PR) were eligible for consolidative stem cell transplantation (SCT) after 4 cycles. Thirty-three stage II–IV PTCL patients were treated: 21 PTCL-not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3–4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2-year progression-free survival and overall survial, were 39% (95% confidence interval 21–57) and 60% (95% confidence interval 39–76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow-up of 21.5 months. CEOP-P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need.

A prospective cohort study of patients with peripheral T‐cell lymphoma in the United States

“…Of note, two recent clinical trials using combination chemotherapy regimens without doxorubicin also did not improve response rates. 23,24 Our findings support the use of anthracyclines as an important part of the induction regimen for patients with nodal PTCL who are being treated with curative intent. 25 Among those expected to tolerate anthracycline treatment, removal of anthracyclines should be attempted only under the auspices of a clinical trial.…”

“…4,23,24 However, we observed that patients who received non-anthracycline regimens had inferior response rates and worse overall survival compared to patients treated with anthracyclines. Confirmation of reduced mortality associated with anthracycline use on multivariate analysis (controlling for IPI score and disease histology) argues against confounding by indication as the primary source of this observation.…”

How I manage peripheral T‐cell lymphoma, not otherwise specified and angioimmunoblastic T‐cell lymphoma: current practice and a glimpse into the future

“…Based on these analyses, phase II/III studies investigating the role of ASCT and alloSCT started treatment with 4–6 courses of CHOEP (d'Amore et al , ), and recent reviews (Moskowitz et al , ) as well as current National Comprehensive Cancer Network NHL guidelines (https://www.nccn.org/professionals/physician_gls/f_guidelines_nojava.asp), European Society for Medical Oncology (d'Amore et al , ) and German/Austrian guidelines (Hopfinger et al , ) mention CHOEP as a (preferable) alternative to CHOP in younger patients treated with curative intent. Chemotherapy consisting of CHOP plus etoposide and gemcitabine (CHOP‐EG) (Kim et al , ), cisplatin, etoposide, gemcitabine and methylprednisolone (PEGS) (Mahadevan et al , ), cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternating with pralatrexate (P) (Advani et al , ) as well as intense regimens like hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (Hyper‐CVAD) (Escalon et al , ) failed to convincingly improve outcomes (Table ). Phase III studies combining CHOP with antibodies, antibody‐drug conjugates (BV), or histone deacetylase (HDAC)‐inhibitors (Ro‐CHOP) and comparing the experimental arm to CHOP are ongoing (NCT 01796002).…”

The potential of pralatrexate as a treatment of peripheral T-cell lymphoma

“…It may be better to substitute anthracycline with etoposide. Preliminary interesting results have been obtained with CEOP, alternating with pralatrexate in frontline therapy for patients with PTCL [58].…”