A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma

A. M. Evens*, K. R. Carson, J. Kolesar, C. Nabhan, I. Helenowski, N. Islam, B. Jovanovic, P. M. Barr, P. F. Caimi, S. A. Gregory, L. I. Gordon

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Despite improvement with intensive multi-agent chemotherapy, 2-year progression-free survival (PFS) rates for adults with high-risk Burkitt's lymphoma (BL) remains <55%. Patients and methods: We conducted a phase II trial for newly diagnosed classic BL utilizing liposomal doxorubicin (Adriamycin) in lieu of doxorubicin and incorporating intravenous rituximab (at 500 mg/m2 twice/cycle) into the CODOXM/IVAC regimen. Correlative analyses included paired serum and cerebrospinal fluid (CSF) rituximab levels and close examination of cardiac function. Results: Among 25 BL patients, the median age was 44 years (23-70) and 4 patients were HIV positive. There were 20 high-risk and 5 low-risk patients. At baseline, 40%of high-risk patients had bone marrow involvement, 35%had bulky disease and 15%had central nervous system involvement. The overall response rate was 100%(complete remission 92%). At 34-month median follow-up, the 2-year PFS and overall survival (OS) rates for all patients were 80%and 84%, respectively (low-risk: both 100%; high-risk: 76% and 81%, respectively). Furthermore, the 2-year PFS, OS, and diseasespecific survival (DSS) rates for high-risk, HIV-negative patients were 84%, 89% and 100%, respectively. Adverse events (AEs) appeared to be consistent with prior CODOX-M/IVAC data, although there were several grade 3 cardiac events noted (all declined ejection fraction without clinical symptoms). The mean serum rituximab levels at 24 h after cycles 1 and 3 for patients without relapse were 258 and 306 μg/ml, respectively, versus 131 and 193 μg/ml, respectively, for patients with early progression (P = 0.002 and 0.002, respectively). The mean CSF rituximab levels for all patients were 0.11 and 0.24 μg/ml, respectively, at cycle 1 (24/72 h), which equated to serum:CSF ratios of 0.05% and 0.20%, respectively. Conclusions: The integration of rituximab into CODOX-M/IVAC for adult BL was feasible and tolerable, while changes in cardiac function warrant continued examination. This regimen was associated with excellent survival rates for HIV-negative BL. Further investigation of the predictive value of serum rituximab is needed. Clinicaltrials.gov NCT00392990.

Original languageEnglish (US)
Pages (from-to)3076-3081
Number of pages6
JournalAnnals of Oncology
Volume24
Issue number12
DOIs
StatePublished - Dec 2013

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Keywords

  • Burkitt's lymphoma
  • Cancer
  • Liposomal doxorubicin
  • Non-Hodgkin's lymphoma
  • Prognosis
  • Rituximab

ASJC Scopus subject areas

  • Hematology
  • Oncology

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