Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial

Abstract

Key Points• Largest prospective trial for adult Burkitt lymphoma/ leukemia patients. • Substantial cure rates and high treatment-realization rates in all age groups.This largest prospective multicenter trial for adult patients with Burkitt lymphoma/ leukemia aimed to prove the efficacy and feasibility of short-intensive chemotherapy combined with the anti-CD20 antibody rituximab. From 2002 to 2011, 363 patients 16 to 85 years old were recruited in 98 centers. Treatment consisted of 6 5-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years old received a reduced regimen. Rituximab was given before each cycle and twice as maintenance, for a total of 8 doses. The rate of complete remission was 88% (319/363); overall survival (OS) at 5 years, 80%; and progression-free survival, 71%; with significant difference between adolescents, adults, and elderly patients (OS rate of 90%, 84%, and 62%, respectively). Full treatment could be applied in 86% of the patients. The most important prognostic factors were International Prognostic Index (IPI) score (0-2 vs 3-5; P 5 .0005), age-adjusted IPI score (0-1 vs 2-3; P 5 .0001), and gender (male vs female; P 5 .004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, even in elderly patients. This trial was registered at www.clinicaltrials.gov as #NCT00199082. (Blood. 2014;124(26):3870-3879)

High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program

“…The GMALL previously reported the results obtained in 185 patients, 8 recently updating their experience in 363 total cases. 19 In patients aged 15-55 years, the 3-year OS was 91% for Burkitt lymphoma and 79% for Burkitt leukemia, representing a significant improvement from prior results obtained with chemotherapy without rituximab. 2 We treated 105 patients with a median age of 47 years and 21% incidence of low aIPI (compared with 54% in a similar CALGB study), 18 achieving OS and DFS rates of 67% (75% for those aged ≤60 years) and 75% (82% for those aged ≤60 years), respectively.…”

“…Toxicity was evaluated according to the Common Toxicity Criteria scale, and the individual PS was assessed according to the ECOG definition. 13 The adapted International Prognostic Index (aIPI), 17 previously validated in BL by two independent studies 18,19 ranged from low (0-1 risk factors) to intermediate (2-3 risk factors) and high (4-5 risk factors). Risk factors were age >60 years, elevated lactate dehydrogenase (LDH) level, ECOG PS >1, clinical stage III-IV, and involvement of >1 extranodal site.…”

Elucidation of tonic and activated B-cell receptor signaling in Burkitt’s lymphoma provides insights into regulation of cell survival

“…We included in our study genetically distinct BL; therefore, our comprehensive datasets, which include numerous time-resolved BCR signaling events, may represent a valuable resource for identifying potential drug targets. This finding is of particular importance because targeted therapies for BL are largely lacking at present and because they would be needed to improve outcomes-both in elderly BL patients, who still have a poor prognosis (38), and in patients with endemic BL in developing countries, where the administration of intensive chemotherapy is still a challenge.…”

Personalized medicine in adult acute lymphoblastic leukemia

“…With repeated short cycles of intensive chemotherapy, combined with rituximab the overall survival of such patients increased from 60% to >80%. 23 Monoclonal antibodies directed against CD22, linked to cytotoxic agents, such as calicheamicin (inotuzumab ozogamicin), or to plant or bacterial toxins (epratuzumab) are being explored for use in refractory/relapsed childhood and adult ALL. In a trial of patients with relapsed/refractory ALL treated with inotuzumab ozogamicin, the complete response rate (including responses without blood cell count recovery) was 66%, and of those 78% achieved a molecular complete remission.…”