OPEC/Mpec for Adult T-Cell Leukemia/Lymphoma: A Single-Institution Study
Authors: Nakamura Daisuke , Yoshimitsu Makoto , Tabuchi Tomohisa , Arima Naosuke , Hayashida Maiko , Inoue Hirosaka , Matsushita Kakushi , Matsumoto Tadashi , Arima Naomichi , Ishitsuka Kenji 
Published: October 2019

Abstract
Introduction
Adult T-cell leukemia/lymphoma(ATL) is a neoplasm of peripheral T-lymphocytes associated with human T-lymphotropic virus typeⅠ(HTLV-1), and its prognosis still remains very poor. VCAP-AMP-VECP, which is a sequential combination chemotherapy consisting of VCAP (vincristine, cyclophosphamide, doxorubicin, and prednisolone), AMP (doxorubicin, ranimustine, and prednisolone), and VECP (vindesine, etoposide, carboplatin, and prednisolone) has been considered to standard of care in Japan for the treatment of aggressive ATL (acute, lymphoma and chronic type with unfavorable prognostic factors) by the result of a phase 3 clinical trial in comparison to CHOP14, however, patients older than 70 years old were excluded from the trial. Since the median age of newly diagnosed ATL in Japan is becoming nearly 70, it is urgent to establish the optimal chemotherapy for elderly patients. We have reported the therapeutic potential of OPEC/MPEC regimen for aggressive ATL, which is a weekly non-anthracycline containing combination chemotherapy consisted by vincristine (0.7 mg/m2), prednisolone (20 mg/m2), etoposide (70 mg/m2), and cyclophosphamide (200 mg/m2) (OPEC). Vincristine is replaced to methotrexate (14 mg/m2) from 7th cycle. After 15thcycle, either of OPEC or MPEC is selected by physicians' choice by considering efficacy and adverse events. We have mainly used OPEC/MPEC regimen until 2010, and VCAP-AMP-VECP regimen thereafter. The aim of this study is to elucidate the therapeutic outcome of patients treated in practice by either of these regimens by retrospective analysis.
Methods
We retrospectively reviewed the therapeutic outcome of the patients who have been diagnosed as aggressive ATL in our hospital between January 2005 and December 2014, and treated with either of OPEC/MPEC or VCAP-AMP-VECP regimens.
Results
Among 220 patients, 138 and 33 patients were treated by either of OPEC/MPEC and VCAP-AMP-VECP regimens, respectively. The distribution of patients by the simplified ATL-PI is shown in Table 1. In younger patients (≦69 years), the 3-year OS was 10.4% (n=58) vs 21.8% (n=20) in OPEC/MPEC and VCAP-AMP-VECP, respectively (P=0.0394) (Figure 1). On the other hand, in the elderly patients (≧70 years), the 3-year OS was 9.8% (n=80) vs 12.7% (n=13), respectively (P=0.841) (Figure 2). Importantly, OPEC/MPEC was less toxic than VCAP-AMP-VECP, grade 3 to 4 of neutropenia (51.4% vs 93.9%), infectious complications defined by febrile neutropenia and/or any documented infections (22.5 % vs 66.7 %) as well as the incidence of decline in the PS after the treatment in comparison to that in the initiation of chemotherapy during the treatment (18.1 % vs 48.5 %). Importantly, the average of relative dose intensity (RDI) in elderly patients treated by VCAP-AMP-VECP was significantly compromised in comparison to those treated by OPEC/MPEC (Table 2, p=0.002).
Conclusions
The overall survival in elderly patients with aggressive ATL treated by OPEC/MPEC was comparable to those treated by VCAP-AMP-VECP. Less dose-intensified treatment such as OPEC/MPEC is an option for future trial for elderly patients with aggressive ATL.

Disclosures
Yoshimitsu: HUYA Bioscience International: Research Funding.