Poster Board I-693
Burkitt lymphoma is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for nearly 3% of all newly diagnosed NHLs. It is unclear whether the addition of the anti-CD20 monoclonal antibody rituximab to CODOX-M/IVAC chemotherapy improves response rates or outcomes. We used an IRB-approved comprehensive clinicopathologic database to identify all adult Burkitt lymphoma patients treated at our institutions from 12/1/1992 through 2/1/2009 with CODOX-M/IVAC for curative intent. Patients who received CODOX-M/IVAC with rituximab were compared to patients treated with CODOX/M-IVAC without rituximab. Primary endpoints were objective response rate (ORR), overall survival (OS) and progression free survival (PFS). Multivariable Cox regression models of OS and PFS were utilized to provide adjusted treatment comparisons and identify simultaneous significant prognostic factors.
Forty patients received R-CODOX-M/R-IVAC, compared to 47 patients treated with CODOX-M/IVAC alone. All patients received white cell growth factor support. The median age was 45 years (17-78), advanced Ann Arbor stage 70%, LDH > upper limit of normal 72%, extra nodal involvement 80% and ECOG PS '2 in 78% of patients. Twelve patients (14%) were low risk defined as a single focus less than 10cm with a normal LDH and 75 (86%) patients were high risk. Fourteen patients (16%) were HIV positive, all of whom received concurrent HAART therapy. Mean CD4 count in HIV positive patients was 237. Seventeen patients (20%) had CNS involvement at diagnosis.
Overall response rate was 90% in patients who received rituximab, and 85% in those who did not (P=0.54, Fisher's exact test). Thirty-six patients (90%) achieved complete response (CR) in the R-CODOX-M/R-IVAC group compared to 38 (81%) in the CODOX-M/IVAC group (P=0.37, Fisher's exact test). At a median follow-up among all patients alive and well (n=56) of 30.4 months (range 1.0-127.8), the progression-free (PFS) and overall survival (OS) for the entire cohort are 66% and 68%, respectively. Median follow-up among patients alive and well (n=29) for the R-CODOX-M/R-IVAC group is 23 months. At 23 months, the PFS and OS for rituximab treated patients are 70% and 73%, respectively, compared to CODOX-M/IVAC patients whose 23 month PFS and OS are 61% and 68% respectively. On univariate analysis of both OS and PFS, neither inclusion of rituximab nor HIV status was found to be statistically significant. Patients with high-risk disease, older than 60 years, or CNS involvement had an inferior overall survival on univariate analysis (P<0.05, log-rank test and Wilcoxon test). Advanced age was associated with poorer OS on multivariable Cox regression analysis (P=0.04).
The addition of 4 doses of rituximab to CODOX-M/IVAC for Burkitt lymphoma did not significantly improve outcome over CODOX-M/IVAC alone, though there was a trend towards improvement in response rate and survival suggesting that increased patient numbers may be needed to demonstrate significance. Whether more doses of rituximab may provide optimal benefit is currently unknown and warrants further study. Advanced age, high-risk disease, and CNS involvement are associated with a worse prognosis, while HIV patients demonstrate no difference in outcome compared to HIV-negative counterparts.
Off Label Use: Rituximab is not specifically approved for Burkitt lymphoma. Hochberg:Enzon: Consultancy, Speakers Bureau; Biogen-Idec: Speakers Bureau; Genentech: Speakers Bureau; Amgen: Speakers Bureau.
Asterisk with author names denotes non-ASH members.