The dose modified (dm) CODOX-M/IVAC protocol for Burkitt Lymphoma (BL) is an iteration of the original treatment regimen described by Magrath et al in 1996.r The intention was to provide a dose intensive, compact, non cross-resistant regimen with effective CNS targeting. The promising results of this study were confirmed in the LY06 study which was a larger, multicentre, international phase 2 trial.r This regimen was refined in the LY10 trial, whereby methotrexate was dose modified to 3 g/m2 (from 6.7 g/m2) in order to reduce toxicity.r LY10 forms the basis of the current eviQ dmCODOX-M/IVAC protocol.
LY10 was a prospective, international, non-randomised phase 2 study that included 53 patients (median age 37 years; range 17 to 76 years) with newly diagnosed BL. Patients with documented CNS involvement received additional intrathecal therapy. The LY10 trial included 11 low risk and 42 high risk patients.r
Patients were considered 'Low Risk' if they had at least 3 of the 4 following international prognostic index (IPI) factors: normal LDH, Ann Arbor stage I to II, WHO performance status 0 to 1 and number of extra nodal sites less than or equal to 1. These patients were treated with three cycles of dmCODOX-M.r
All other patients were considered 'High Risk' and received alternating cycles of dmCODOX-M/IVAC twice. Seventy-six percent of the patients were able to complete the planned therapy. Severe (grade 3/4) toxicities included neutropenia (99%), neutropenic fever (80%), thrombocytopenia (86%), mucositis (47%), and neuropathy (8%). The treatment related death rate was 8%. Two year progression free survival (PFS) and overall survival (OS) rates were 64% and 67%, respectively.r
In recent years it has been common practise for rituximab to be added to the dmCODOX-M/IVAC regimen, though there has been no prospective randomised evaluation of the efficacy of this addition. The largest prospective studyr utilised rituximab 375 mg/m2 on day 1 of each dmCODOX-M and IVAC cycle. 15 patients with BL and 15 with unclassifiable lymphomas intermediate between BL and diffuse large B cell lymphoma were evaluated. This regimen was associated with acceptable toxicity and outcomes commensurate with historical dmCODOX-M/IVAC patients who were not exposed to rituximab. Several other groups have reported retrospective data on CODOX-M/IVAC based regimens combined with rituximab.rrr In view of this data, addition of rituximab seems reasonable, though ideal timing and dosing remains to be defined.
HIV-Associated Burkitt Lymphoma
HIV-associated Burkitt Lymphoma is a rare clinical entity outside of specialized centres. There is no consensus regarding optimum treatment regimen, and CODOX-M/IVAC is one option employed.
There is limited data regarding the use of CODOX-M/IVAC in HIV-associated Burkitt Lymphoma. Wang et. al.rreported retrospective outcomes of 14 adults with complete response rate of 63%. The AIDS Malignancy Consortiumr reported prospective outcomes in 34 patients, using a modified regimen, and PFS at one year was 69% with OS 72%.
Progression-free survival and overall survival in the LY06r and LY10r studies, with risk group defined as in LY10:
© Blood 2008
In the LY10 study,r there were 9 deaths (1 low risk, 8 high risk) reported to be treatment-related, of which 5 (all high-risk patients) died within 12 weeks of starting treatment; 2 of the 9 patients were aged over 65 (66 and 67, respectively).
© Blood 2008