Rituximab and Liposomal Doxorubicin Improve Progression-Free and Overall Survival When Added to Chemotherapy in Untreated Burkitt's Lymphoma
SAN DIEGO, CA—At the 53rd American Society of Hematology Annual Meeting and Exposition, study investigators presented evidence demonstrating promising survival rates in Burkitt's lymphoma (BL) when rituximab was added to the CODOX-M and IVAC chemotherapy regimens and when liposomal doxorubicin was used in place of doxorubicin in the CODOX-M regimen.
Andrew M. Evens, DO, MSc, of The University of Massachusetts Medical School, Worcester, and colleagues conducted a five-site Phase 2 study that included patients with newly diagnosed BL and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and BL (following the WHO 2008 definition), regardless of HIV status. HIV+ patients in the study had no evidence of multidrug-resistant HIV infection or concurrent AIDS-defining illness with a CD4 count >350/mcL. Patients were defined as low-risk if they met the following criteria: normal lactate dehydrogenase (LDH), stage I/II disease, ECOG performance status <2, and no mass >10cm; all other patients were classified as high-risk.
Low-risk patients received three consecutive cycles of CODOX-M, whereas high-risk patients received four alternating cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate) and IVAC (ifosfamide + etoposide + high-dose cytarabine). The CODOX-M regimen included methotrexate 3g/m 2 IV; liposomal doxorubicin 40mg/m2 was used instead of doxorubicin on Day 1 of all cycles of this treatment. Intravenous rituximab 500mg/m2 was added to Days 0 and 8 of each CODOX-M cycle and Days 0 and 6 of the IVAC cycle.
Of 25 patients enrolled, there were 20 high-risk and 5 low-risk patients. Three of the high-risk and one low-risk patient were HIV+. All patients had classical BL, while one patient had concomitant BCL-2 expression. Additionally, seven (35%) high-risk patients had bulky disease >10 cm (two [10%] with dominant mass >20cm), eight (40%) patients had bone marrow involvement, and 15 (75%) had an elevated LDH. Therapy was completed at an average of 13.5 weeks (range 11–20) for high-risk patients and an average of 10 weeks for low-risk patients (range 9–12).
The response rate after two cycles of chemotherapy was 100%. There was a 78% complete remission (CR) rate. After an average follow-up of 24 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates for all patients were 86% and 86%, respectively. Low-risk 2-year PFS and OS were both 100%. High-risk 2-year PFS and OS were both 82%. The 2-year PFS and OS rates for high risk, HIV-negative patients were both 91%; the disease-specific survival for this subgroup of patients was 100%.
After two cycles of therapy, two Grade 2 and two Grade 3 cardiac events were noted (all depressed ejection fraction (EF), no clinical evidence of congestive heart failure). The two Grade 3 events occurred in two men with high-risk disease, 70 years and 69 years of age, the latter with history of myocardial infarction. Among all patients, the median change in EF from baseline was -2% (range -22–11%). The occurrence of Grade 4 myelosuppression and Grades 3–4 mucositis were comparable to prior CODOX-M/IVAC results. Other Grade 3 toxicities included infection, neutropenic fever, transaminitis, diarrhea, elevated creatinine, and seizure. No other Grade 4 adverse events were present. Three deaths occurred during the study, two cases of progressive disease in HIV+ high-risk patients, one from unknown causes.
”The integration of retuximab and liposomal doxorubicin into CODOX-M/IVAC for adult BL was feasible and associated with similar tolerability compared with prior reports. Additionally, this regimen was associated with excellent survival rates, especially for HIV-negative BL,” the study authors concluded.