Phase II study of HCVIDD/MA in patients with newly diagnosed peripheral T‐cell lymphoma

A phase II study was performed to evaluate the efficacy of hyper‐fractionated cyclophosphamide, vincristine, pegylated liposomal doxorubicin and dexamethasone alternating with methotrexate/cytarabine (HCVIDD/MA) in patients with newly diagnosed peripheral T‐cell lymphoma (PTCL), excluding ALK‐positive anaplastic large cell lymphoma. Fifty‐three patients were enrolled. Treatment was planned for up to 8 cycles but only 9% of patients received more than 6 cycles due primarily to disease progression (n = 13) or prolonged thrombocytopenia (n = 12). The overall response rate was 66% with a complete response rate of 57%. Median progression‐free survival (PFS) was 7·5 months. With a median follow‐up of 7·6 years, 5‐year PFS and overall survival (OS) were 21% and 48%, respectively. The patients with extranodal Natural Killer‐cell lymphoma had a shorter PFS (median, 2·4 months) than other subtypes. Grade 3/4 anaemia, neutropenia and thrombocytopenia were observed in 66%, 74% and 79% of patients, respectively. Of note, 23% of patients discontinued therapy due to prolonged thrombocytopenia. In conclusion, HCVIDD/MA for the first‐line treatment of PTCL patients is associated with significant myelosuppression leading to poor treatment adherence, and the response and survival outcomes with this regimen are similar to standard CHOP. This study was registered at www.clinicaltrials.gov as #NCT00290433.

[1]  Michael L. Wang,et al.  Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. , 2015, Clinical lymphoma, myeloma & leukemia.

[2]  Sonali M. Smith,et al.  Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy. , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  N. Schmitz,et al.  Allogeneic and autologous stem cell transplantation for hepatosplenic T-cell lymphoma: a retrospective study of the EBMT Lymphoma Working Party , 2014, Leukemia.

[4]  M. Jerkeman,et al.  Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. , 2014, Blood.

[5]  A. Zelenetz,et al.  A retrospective analysis of peripheral T-cell lymphoma treated with the intention to transplant in the first remission. , 2013, Clinical lymphoma, myeloma & leukemia.

[6]  J. Delabie,et al.  Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  C. Flowers,et al.  A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma , 2011, ISRN hematology.

[8]  A. Rosenwald,et al.  Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. , 2010, Blood.

[9]  J. Rossi,et al.  Upfront VIP‐reinforced‐ABVD (VIP‐rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS‐LTP95 , 2010, British journal of haematology.

[10]  D. Weisenburger,et al.  Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project. , 2009, Blood.

[11]  D. Weisenburger,et al.  International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  N. Shinton.  WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues , 2007 .

[13]  A. Zelenetz,et al.  Intensive induction chemotherapy followed by early high-dose therapy and hematopoietic stem cell transplantation results in improved outcome for patients with hepatosplenic T-cell lymphoma: a single institution experience. , 2007, Clinical lymphoma, myeloma & leukemia.

[14]  Sigrid Stroobants,et al.  Revised response criteria for malignant lymphoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  H. Kantarjian,et al.  Chemoimmunotherapy with hyper‐CVAD plus rituximab for the treatment of adult Burkitt and Burkitt‐type lymphoma or acute lymphoblastic leukemia , 2006, Cancer.

[16]  Michael L. Wang,et al.  High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Terry L. Smith,et al.  Prognostic factors and treatment of patients with T‐cell non‐Hodgkin lymphoma , 2005, Cancer.

[18]  R. Gascoyne,et al.  Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[19]  E. Iannitto,et al.  Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. , 2004, Blood.

[20]  P. Gaulard,et al.  Hepatosplenic γδ T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients , 2003 .

[21]  J. Armitage,et al.  Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  P. Mclaughlin,et al.  Alternating triple therapy for the treatment of intermediate grade and immunoblastic lymphoma. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[23]  P F Thall,et al.  Practical Bayesian guidelines for phase IIB clinical trials. , 1994, Biometrics.

[24]  Emili Montserrat,et al.  A predictive model for aggressive non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.

[25]  T M Grogan,et al.  Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.

[26]  N. Schmitz,et al.  Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  D. Weisenburger,et al.  Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. , 2006, Blood.

[28]  P. Gaulard,et al.  Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. , 2003, Blood.