ALBERT

Description: Introduction R-CHOP is the standard of care for patients with diffuse large B cell lymphoma (DLBCL) however poor risk patients (IPI 3-5) still have an inadequate outcome. Neither first remission high dose chemotherapy and peripheral blood stem cell transplantation (HDC+PBSCT) nor selection of cases for intensification by interim PET scanning have demonstrated a proven benefit. In the case of Burkitts lymphoma (BL) there is a paucity of data on the addition of Rituximab to the CODOX-M and IVAC regimen. Patients and Methods 113 patients with DLBCL and 37 with BL were recruited from 53 UK sites between May 2008 and April 2013. Median age was 49 years (18-65). For DLBCL patients IPI scores were 3 – 72 ( 64%), 4 -40 (35%) and 5 – 1 (1%). All patients received the modified CODOX-M and IVAC regimen including all CNS directed therapy( Mead et al Ann Oncol. 2002 Aug;13(8):1264-74) and 8 doses of rituximab. The primary end point of the study was Progression Free survival (PFS) and secondary endpoints included toxicity and CR rate. Results The main toxicities reported were neutropenia ( 89% grade 3 or 4), thrombocytopenia (84.2% grade 3 or 4), infection 61.6% grade 3 or 4 and mucositis (30.1% grade 3 or 4). 4 patients were excluded from toxicity assessment as they did not start therapy after registration. There were 8 treatment related deaths observed (infection with neutropenia (5), GI haemorrhage (1), acute cerebral haemorrhage (1) and bowel perforation (1) ). 78 patients with DLBCL and 31 with BL have completed all therapy ( 78.5 % of patients with available data) with an overall response rate of 92 % for DLBCl and 94% for BL. In patients who completed all therapy CR was achieved in 34 (44%), CR (u) in 8 (10%) and PR in 30 (38%) for DLBCL patients and CR was achieved in 21 (68%), CR (u) in 6 (19%) and PR in 2 (6%) in BL patients. 3 patients ( 2 DLBCL and 1 BL) who progressed during therapy have been included in the response analysis. End of treatment PET scanning was not obligatory. 80 patients with DLBCL and 30 patients with BL remain alive and without progression at a median follow up of 18.6 and 19.3 months respectively. Conclusion The R-CODOX-M -R-IVAC regimen can be delivered to patients with poor risk DLBCL in a multicentre setting. High rates of haematological toxicity and consequent infection are inevitable with treatment of this intensity but appear acceptable when compared with other treatments such as HDC+PBSCT. Response rates are encouraging in view of the very poor risk IPI profile of the patients included in this study. Burkitts lymphoma patients also achieved an excellent response rate with no apparent additional toxicity attributable to the addition of rituximab to the regimen. We currently plan the first analysis for the primary endpoint of PFS in 2015. The Trial was supported by Leukaemia and Lymphoma Research (LLR). Disclosures: McMillan: Roche: Consultancy, Honoraria; Amgen: Research Funding. Off Label Use: Rituximab usage in Burkitts Lymphoma. Ardeshna:Roche: Honoraria, Research Funding. Jack:Roche/Genentech: Research Funding. Patmore:Roche: Consultancy, Honoraria. Pettengell:Roche: Honoraria; Amgen: Honoraria. Linch:Roche: Honoraria, Research Funding.

Description: Abstract 3642 Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a rare disease accounting for 1–2% of all non-Hodgkin's lymphomas. It characteristically has an aggressive course with poor prognosis and a median overall survival (OS) in the order of 3 years. The median age at presentation is 65–70 years and most patients present with advanced stage disease. Due to its low incidence, few prospective clinical trials have been performed and the optimal treatment is not known. There is evidence that purine analogues are efficacious in AITL and the combination of fludarabine and cyclophosphamide (FluCy) has a high level of efficacy in other lymphoproliferative disorders. There are also good theoretical reasons and preliminary evidence to support the use of thalidomide in AITL. This multi-centre, phase II trial was designed to assess the efficacy and tolerability of FluCy chemotherapy and incremental response to consolidation with 6 months of thalidomide treatment. Methods: Using a Bayesian 2-stage design, it was planned to recruit 15 patients with a further 22 patients recruited to a second stage if a complete remission (CR) rate of 〉33% was achieved. Inclusion criteria were previously untreated AITL with measurable disease, performance status 18 years, and valid consent. The primary endpoint was response rate to FluCy. Secondary endpoints were response rate to thalidomide, toxicity, progression free survival (PFS), and OS. Treatment consisted of fludarabine 40mg/m2 and cyclophosphamide 250mg/m2 orally on days 1–3 of each 28 day cycle. Four cycles of FluCy were given prior to restaging. Patients progressing on FluCy came off study. Those with stable disease or responses had the option of 2 further cycles of FluCy prior to commencing thalidomide maintenance. Thalidomide 100mg once daily was given as continuous therapy starting 4 weeks after the final cycle of FluCy, with dose increases every 4 weeks to 300mg if tolerated. Results: 15 patients were recruited from 6 centres over 3 years from February 2009 to March 2012. The median age was 68 years (range 52–91) with more female than male patients (67% vs. 33%). 87% of patients had advanced stage disease. Four or more cycles of FluCy were administered in 53% of patients. Responses (CR, CRu, PR) were achieved in 9 patients (60%) with CR in 5 (33%). Reasons for early cessation of treatment were hematological toxicity (n=2), death (n=2) and failure to respond (n=3). Grade 3 or 4 hematological toxicity occurred in 8 (53%) patients, grade 3 or 4 non-hematological toxicity was experienced in 9 (60%) patients. Grade 1–2 peripheral neuropathy was reported in 2 patients. Guillain-Barré syndrome was reported in 2 patients in the thalidomide maintenance phase but resolved in both cases. Of the 9 patients with at least stable disease after FluCy, 7 received thalidomide, 2 patients did not receive thalidomide due to hematological toxicity and progression respectively. Remission status did not improve in any patients receiving thalidomide maintenance (6 patients progressed or have died and remission status was unchanged in the remaining patient). At a median follow-up of 14.9 months, 8 patients (53%) are alive. The estimated median OS is 18.2 months and median PFS is 7.9 months. Of the patients still alive, 4 have progressed, 2 (13%) are alive without progression, and 2 are not assessable for response due to early termination of treatment. The causes of death in the 7 deceased patients were lymphoma (5), infection (1), and Crohn's disease (1). Discussion: AITL is an aggressive lymphoma with poor outcome. The overall response rate in this trial of 60% (CR rate of 33%) was promising but remissions were short lived with a PFS of only 7.9 months. Only 2 patients are alive without progression at a median follow-up of 14.9 months. Thalidomide maintenance did not consolidate remission in any patients. The trial did not proceed to the 2nd stage of recruitment and demonstrates the difficulties in conducting prospective clinical trials in rare disorders such as AITL. The CR rate and duration of remission observed with FluCy are inferior to those reported with CHOP-type regimens. On the basis of these results, we recommend considering FluCy as first line treatment for AITL only when CHOP is contraindicated. Also, we found no evidence to support the use of thalidomide in this disease. Disclosures: Off Label Use: Thalidomide is used off licence in the trial for the treatment of AITL.