RD‐CODOX‐M/IVAC with rituximab and intrathecal liposomal cytarabine in adult Burkitt lymphoma and ‘unclassifiable’ highly aggressive B‐cell lymphoma

Abstract

Summary Specific trials on adult Burkitt lymphoma (BL) and ‘unclassifiable’ lymphomas with features intermediate between BL and diffuse large B‐cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX‐M/IVAC (CODOX‐M: cyclophosphamide, vincristine, doxorubicin, high‐dose methotrexate; IVAC: ifosfamide, etoposide and high‐dose cytarabine) regimen by the addition of rituximab (R) and liposome‐encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60 years) with BL (n = 15) and BL/DLBCL (n = 15) were accrued. Primary endpoints were progression‐free survival (PFS), CNS recurrence, and liposomal cytarabine‐associated toxicity. Eighty percent of patients received the whole treatment programme, the remaining cases received at least three full courses. Application of the RD‐CODOX‐M/IVAC regimen resulted in remarkable 4‐year PFS (78%) and complete remission (CR) rates (93%). However, PFS was significantly lower in patients older than 60 years as compared to younger ones (49%vs 93%, P = 0·03; median, 36 months), despite high actual dose‐intensity, CR rate and tolerability. Reduced‐intensity intratechal prophylaxis through liposomal cytarabine was effective because the CNS failure rate was low (3·4%) and without severe neurological toxicities. The RD‐CODOX‐M/IVAC strategy is feasible and highly effective, but improving outcomes in elderly patients remains a priority.

Trends in survival of patients with Burkitt lymphoma/leukemia in the USA: an analysis of 3691 cases

“…In fact, among 4 series reporting the outcomes of BL patients treated with modern immunochemotherapy, the median age ranged from 46 to 52 years and 3-year survival from 82% to 89%. [7][8][9][10] This is in sharp contrast with the 2002-2008 cohort reported here in which, despite lower median age (43 years), the 3-year survival was only 56%. Possible factors affecting this difference are selection bias and unequal access to tertiary medical centers able to deliver the complex treatment plan and supportive care required for effective BL management.…”

“…[1][2][3][4] More recent series and clinical trials report success rates in excess of 90% in pediatric 4,5 and 80% in adult populations. [6][7][8][9] The anti-CD20 monoclonal antibody rituximab has transformed the management of other mature B-cell malignancies. Because BL cells express abundant surface CD20, rituximab has been incorporated in multiple recent regimens reporting high success rates.…”

“…Because BL cells express abundant surface CD20, rituximab has been incorporated in multiple recent regimens reporting high success rates. 7,8,10 However, its impact on the management of BL has not been properly evaluated.…”

Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)

“…IT LC maintains cytotoxic concentrations in CSF for up to 14 days after a single IT injection, 76,77 but is not licensed for prophylactic use. 11 The efficacy and toxicity of LC in the prophylaxis of CNS involvement specifically in DLBCL has only been analyzed in two recently published studies.…”

An Innovative Cis-Diammineplatinum (II) Benzene-Polycarboxylic-Acids Complex Inhibits Growth of Burkitt`s Cell Lymphoma In Vitro and In Vivo

“…Concerning treatment of BL there are no authorized treatment guidelines for this condition available. There are individual clinical and research publications that support treatment regimens like CHOP, R-CHOP, R-CCODOX-M/R-IVAC, R-BFM and R HyperCVAD/HDAraC+Methotraxate [7][8][9].…”