A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma

Br J Haematol. 2015 Nov;171(4):539-46. doi: 10.1111/bjh.13637. Epub 2015 Aug 7.

Abstract

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/m(2) ) 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.

Keywords: bortezomib; follicular lymphoma; indolent lymphoma; neuropathy; non-Hodgkin lymphoma.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / adverse effects
  • Bortezomib / therapeutic use
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced
  • Prednisone / administration & dosage
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Thrombocytopenia / chemically induced
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Rituximab
  • Vincristine
  • Bortezomib
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol