AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated Burkitt lymphoma

Abstract

• We report the first dedicated prospective study in HIV-Burkitt lymphoma demonstrating safety and efficacy in a multiinstitutional setting.• We offer a new therapeutic option by modifying an existing regimen and making it much less toxic.The toxicity of dose-intensive regimens used for Burkitt lymphoma prompted modification of cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for HIV-positive patients. We added rituximab, reduced and/or rescheduled cyclophosphamide and methotrexate, capped vincristine, and used combination intrathecal chemotherapy. Antibiotic prophylaxis and growth factor support were required; highly active antiretroviral therapy (HAART) was discretionary. Thirteen AIDS Malignancy Consortium centers enrolled 34 patients from 2007 to 2010. Median age was 42 years (range, 19-55 years), 32 of 34 patients were high risk, 74% had stage III to IV BL and CD4 count of 195 cells per mL (range, 0-721 cells per mL), and 5 patients (15%) had CD4 <100 cells per mL. Twenty-six patients were receiving HAART; viral load was <100 copies per mL in 12 patients. Twenty-seven patients had at least one grade 3 to 5 toxicity, including 20 hematologic, 14 infectious, and 6 metabolic. None had grade 3 to 4 mucositis. Five patients did not complete treatments because of adverse events. Eleven patients died, including 1 treatment-related and 8 disease-related deaths. The 1-year progressionfree survival was 69% (95% confidence interval [CI], 51%-82%) and overall survival was 72% (95% CI, 53%-84%); 2-year overall survival was 69% (95% CI, 50%-82%). Modifications of the CODOX-M/IVAC regimen resulted in a grade 3 to 4 toxicity rate of 79%, which was lower than that in the parent regimen (100%), without grade 3 to 4 mucositis. Despite a 68% protocol completion rate, the 1-year survival rate compares favorably with 2 studies that excluded HIV-positive patients. This trial was registered at http:// clinicaltrials.gov as #NCT00392834. (Blood. 2015;126(2):160-166)

Durable survival after chemotherapy in a HIV patient with Burkitt’s lymphoma presenting with massive upper gastrointestinal bleeding

“…The CODOX-M/IVAC regimen was modified by adding rituximab, reducing and rescheduling administration of cyclophosphamide and methotrexate, and lowering the dose of vincristine. 26 This modified regimen resulted in a 1-year progression free survival rate of 69.3%; and the OS rate was 72.2% at 1 year and 69.0% at two years. Only one patient died of treatment-related toxicity.…”

“…25 The R-CODOX-M/IVAC (risk-adapted) regimen had encouraging results even in a cohort where 12% of recruited patients had active CNS disease at diagnosis, and was associated with low treatment-related mortality. 26 In conclusion, massive upper GI bleeding is an uncommon presentation of Burkitt's lymphoma in HIV/AIDS patients, and generally associated with reduced survival. However, the combination of HAART and intensive chemotherapy regimen can achieve cure of the lymphoma and durable survival in these patients.…”

“…None of the patients died from Burkitt's lymphoma or treatment-related toxicity. 25 However, SC-EPOCH-RR is An interesting recent development has been the use of a risk-adapted form of the CODOX-M/IVAC regimen by Noy et al 26 in 34 HIV-positive patients. The CODOX-M/IVAC regimen was modified by adding rituximab, reducing and rescheduling administration of cyclophosphamide and methotrexate, and lowering the dose of vincristine.…”

“…The CNS prophylaxis strategy and outcomes of the major studies in HIV-associated Burkitt's lymphoma are summarised in Table 1. [23][24][25][26][27][28][29] A retrospective study suggested that CODOX-M/ IVAC regimen was equally effective in HIV-positive and negative patients with Burkitt's lymphoma. 23 HIV-positive patients treated with CODOX-M/IVAC tolerated chemotherapy well with similar rates of myelosuppression and infectious complications as HIV-negative patients.…”

“…[23][24][25][26][27][28][29] Different chemotherapeutic protocols have different CNS prophylaxis strategies. The CNS prophylaxis strategy and outcomes of the major studies in HIV-associated Burkitt's lymphoma are summarised in Table 1.…”