A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma
Jonathon B. Cohen
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorJeffrey M. Switchenko
Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
Search for more papers by this authorJean L. Koff
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Search for more papers by this authorRajni Sinha
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorJonathan L. Kaufman
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorH. Jean Khoury
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorNassoma Bumpers
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorAmanda Colbert
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorAmanda Hutchison-Rzepka
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorLoretta J. Nastoupil
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Search for more papers by this authorLeonard T. Heffner
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorAmelia A. Langston
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorMary Jo Lechowicz
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorSagar Lonial
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorCorresponding Author
Christopher R. Flowers
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Correspondence: Christopher R. Flowers, Director, Lymphoma Program, Associate Professor, Department of Hematology & Medical Oncology, Emory University School of Medicine, 1365 Clifton Road, NE, Atlanta, GA 30322, USA.
E-mail: [email protected]
Search for more papers by this authorJonathon B. Cohen
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorJeffrey M. Switchenko
Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA
Search for more papers by this authorJean L. Koff
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Search for more papers by this authorRajni Sinha
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorJonathan L. Kaufman
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorH. Jean Khoury
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorNassoma Bumpers
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorAmanda Colbert
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorAmanda Hutchison-Rzepka
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorLoretta J. Nastoupil
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Search for more papers by this authorLeonard T. Heffner
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorAmelia A. Langston
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorMary Jo Lechowicz
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorSagar Lonial
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Search for more papers by this authorCorresponding Author
Christopher R. Flowers
Hematology and Medical Oncology, Emory University, Atlanta, GA, USA
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Correspondence: Christopher R. Flowers, Director, Lymphoma Program, Associate Professor, Department of Hematology & Medical Oncology, Emory University School of Medicine, 1365 Clifton Road, NE, Atlanta, GA 30322, USA.
E-mail: [email protected]
Search for more papers by this authorSummary
Bortezomib-containing combinations are active in non-Hodgkin lymphoma (NHL) although peripheral neuropathy can limit their dose intensity. Based on our phase I findings, we conducted a phase II trial of bortezomib in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with a modified dose of vincristine. Patients with untreated indolent NHL received bortezomib (1·6 mg/m2) on days 1 and 8 of a 21-day cycle for up to 8 cycles and R-CHOP with a 1·5 mg cap of vincristine. Patients achieving a complete response (CR) received maintenance rituximab, and remaining patients received maintenance rituximab and bortezomib. The primary endpoint was CR rate; secondary survival analyses were evaluated using the Kaplan–Meier method. Among 29 eligible patients, NHL morphologies included follicular (n = 20), marginal zone (n = 5) and small lymphocytic lymphoma (n = 4). Nineteen patients had CR (66%) and 10 had partial response (34%), yielding a 100% overall response rate. With a median follow-up of 48·7 months, the 4-year progression-free and overall survivals were 83% and 93%. Twenty-two patients experienced peripheral neuropathy of any grade, and two had grade 3 neuropathy. The combination of bortezomib with R-CHOP is effective for indolent NHL, and we plan to evaluate therapies incorporating novel proteasome inhibitors in future studies in NHL.
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