A Phase II Study of THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) in Patients with Newly Diagnosed Advanced Peripheral T-Cell Lymphoma: THP-3 Study of Japan Hematopoietic Malignancy Clinical Study Group (HMCSG)

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BackgroundAlthough CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) has been established as a standard of care in patients (pts) with newly diagnosed peripheral T-cell lymphoma (PTCL), new treatment regimen or strategy has been awaited since the outcome of pts with PTCL treated with CHOP is still poor. Pirarubicin (THP) is, an anthracycline drug, which is not affected by the multidrug resistance mediating p-glycoprotein, and is less cardiotoxic than doxorubicin. THP exhibits activity against some doxorubicin-resistant cell lines.ObjectiveA multicenter phase II study was conducted to evaluate the efficacy and toxicity of THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) therapy in pts with newly diagnosed PTCL by Japan Hematopoietic Malignancy Clinical Study Group.Patients and MethodsEligibility criteria were as follows; newly diagnosed PTCL including PTCL-not otherwise specified (NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL); clinical stage of bulky II, III or IV; aged 20 to 79 years; PS 0-2 by ECOG's scale. THP-COP consists of pirarubicin (50mg/m2 on Day1), cyclophosphamide (750mg/m2 on Day1), vincristine (1.4mg/m2 max. 2mg, on Day 1) and prednisolone (100mg on Days 1 to 5) every 3 weeks up to 8 cycles in younger pts less than 69 years, and 6 cycles in elderly pts aged 70 to 79 years, The primary endpoint was complete response rate (%CR) including unconfirmed CR (CRu). The planned sample size was 40 pts, which provided at least 80% power with the expected %CR of 55%, threshold of 35%, and a one-sided α of 5%.ResultsFrom October 2007 to December 2012, 41 pts with a median age of 63 (21-77) yrs were enrolled. The numbers of pts with PTCL-NOS, AITL and ALCL was 21 (51%), 14 (34%) and 6 (15%), respectively. The numbers of stage II bulky, III and IV was 2 (5%), 22 (54%) and 17 (41%), respectively.Fifty-four % were International Prognostic Index high/intermediate or high risk. The %CR including %CRu and overall response rate were 51.2% (90% CI; 37.4-64.9) which met the primary endpoint, and 70.7% (95% CI; 54.5-83.9), respectively. The progression-free survival and overall survival at 3 years (3-yr PFS and 3-yr OS) were 43.5% (95% CI; 27.5-58.4) and 62.9% (95% CI; 43.3-77.4), respectively. Most common Grade 4 toxicities were hematologic: %Grade 4 neutropenia and thrombocytopenia were 80.5% and 9.8%, respectively. Cardiac adverse events were observed in 2 patients with Grade 1 arrhythmia. No secondary malignancies were observed.ConclusionsIn pts with untreated advanced PTCL including PTCL-NOS, AITL and ALCL, THP-COP demonstrated high efficacy with durable PFS and OS and acceptable toxicity profiles. Further large-scaled randomized study to compare with CHOP is warranted. DisclosuresOgura:Celgene: Consultancy, Honoraria; Mundipharma: Consultancy; Takeda: Consultancy, Honoraria; Astrazeneca: Honoraria; SymBio: Consultancy, Research Funding; Celltrion, Inc: Consultancy, Honoraria; MeijiSeika Pharma: Consultancy. Ohmachi:Kyowa Hakko Kirin Co., Ltd.: Honoraria; Eisai Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Pfizer Inc: Honoraria; Takeda Pharmaceutical Co., Ltd: Honoraria. Suzuki:MundiPharma: Consultancy; Chugai Pharmaceutical: Honoraria; Sawai Pharmaceutical: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Mochida Pharmaceutical: Honoraria; MSD: Honoraria; Jazz Pharmaceuticals: Consultancy; Kyowa-Hakko Kirin: Honoraria; Shionogi: Honoraria; Meiji Seika Pharma: Honoraria; Ohtsuka: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Takeda Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Gilead Sciences: Consultancy. Atsuta:Otsuka Pharmaceutical Co., Ltd.: Honoraria. Ohyashiki:Chugai: Research Funding; Dainippon Sumitomo: Honoraria; Nippon Shinyaku: Honoraria; Celegen: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Novartis pharma: Honoraria; Novartis: Research Funding; Asteras: Research Funding; Taiho pharmaceutical: Honoraria; Alexion: Honoraria; MSD: Honoraria; Otsuka pharmaceutical: Honoraria; Jansen Pharma: Honoraria, Research Funding; Pfizer: Honoraria; Fujirebio: Honoraria; KyowaHakko Kirin: Honoraria, Research Funding. Hidaka:Chugai: Research Funding; Eisai: Honoraria. Ando:NIHON PHARMACEUTICAL: Other: Donation to institute; Nippon Shinyaku: Other: Donation to institute; Japan Blood Products Organization: Other: Donation to institute; Takeda: Other: Donation to institute; ALEXION: Other: Donation to institute; Kyowa Hakko Kirin: Other: Donation to institute; MSD: Other: Donation to institute; Bristol-Myers Squibb: Other: Donation to institute; Eisai: Other: Donation to institute; Sumitomo Dainippon Pharma: Other: Donation to institute; CHUGAI PHARMACEUTICAL: Other: Donation to institute; Meiji Seika Pharma: Other: Donation to institute; NOVARTIS: Other: Donation to institute; MOCHIDA PHARMACEUTICAL: Other: Donation to institute; TOYAMA CHEMICAL: Other: Donation to institute; TAIHO: Other: Donation to institute; Asahi KASEI: Other: Donation to institute. Fukuhara:Nihon Ultmarc, Astellas, AbbVie, Alexionpharma, Bayer Yakuhin, Bristol-Myers Squibb, Baxalta, Celgene, Chugai, Daiichi-Sankyo, Toehringer Ingelheim, Eisai, GlaxoSmithKline, Janssen, Japan Blood Products Organization, Kyowa Hakko Kirin, Mitsubishi Tanabe, : Research Funding; Eisai, Janssen, Takeda, Ono and Zenyaku Kogyo: Honoraria. Morishita:Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria. Tsukasaki:Takeda: Honoraria, Research Funding; Kyowa-Kirin: Honoraria; DaiichiSankyo: Consultancy; Zenyaku Kogyo: Honoraria; Celgene: Honoraria, Research Funding; Mundypharma: Research Funding; HUYA: Honoraria; Chugai/Roche: Honoraria. Ozawa:Kyowa Hakko Kirin: Honoraria; Janssen Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria. Hotta:SymBio: Consultancy; SellSeed: Other: outside director; Jansen Pharma: Honoraria; Meiji Seika Pharma: Honoraria; Zenyaku Kogyo: Honoraria. Kinoshita:Chugai: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Jansen Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Eisai: Honoraria; Bristol-Meier's-Squib: Honoraria; Solaisia: Research Funding; MSD: Research Funding; Takeda: Research Funding.