ALBERT

Description: Abstract 1630 The management of recurrent or refractory Hodgkin's lymphoma (HL) remains challenging. Previous published data have suggested that infiltrating normal B lymphocytes in classic HL lesions may contribute to the survival of Hodgkin and Reed-Sternberg cells in vivo. The objective of this prospective, multicenter, phase II trial was to investigate the activity of an anti-CD20 monoclonal antibody, ofatumumab, in combination to a standard platinum-based salvage regimen, ESHAP (O-ESHAP) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) for patients with classical HL failing to first line chemotherapy. Forty- five patients (25 M / 21 F, median age 34 years, range 18–66) were enrolled in the study between June 2010 and June 2012. Treatment consisted on three cycles of ESHAP plus ofatumumab 1,000 mg days 1 and 8 on first cycle and day 1 on second and third cycles. At the time of study entry, 66% of patients had III-IV Ann Arbor stage, 16% bulky disease, 18% B symptoms, 40% extranodal HL and 52% ≥3 involved nodal areas. We respect to response to first-line therapy, 46% patients had achieved a completed response (CR) and then relapsed, 6% had a partial remission (PR), whereas the remaining 48% were primary refractory. Eighty-one percent patients have received 3 cycles of O-ESHAP as scheduled, three patients 2, and five 1 cycle (1 patient due to toxicity, 1 patient's decision, 2 HL progression, and 4 treatments ongoing). Grade 3–4 WHO hematological toxicity was observed in 16%, 19%, and 20% after cycles 1, 2, and 3, respectively. Non-hematological toxicity was reported in 32%, 10%, and 20%, respectively. Overall response (OR) rate was 63% (49% CR and 14% PR). Response to O-ESHAP according to prior response to first-line chemotherapy is shown in table 1. Adequate PBSCs collection was achieved in 94% mobilized patients. Twenty-six out of 33 patients have already proceeded to ASCT. Two patients died of neutropenic sepsis after ASCT and HL progression, respectively. Preliminary results of this ongoing trial suggest that addition of ofatumumab to ESHAP is safe and has a promising clinical activity in patients with relapsed/refractory HL candidates to ASCT. Table 1. Response to O-ESHAP according to previous response to first-line treatment Response to first-line chemotherapy Relapsed or partial response (n=17) Refractory (n=16) Response after O-ESHAP OR 16 (94%) 7 (44%) CR 14 (82%) 3 (22%) PR 2 (12%) 4 (22%) Refractory 1 (6%) 9 (56%) Disclosures: No relevant conflicts of interest to declare.

Description: Background: Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory disease after rituximab-containing first-line therapy have poor outcomes with current salvage regimens. Accordingly, prospective studies incorporating new agents are needed for these patients. We conducted a phase 1b/2 trial to analyze the safety and efficacy of lenalidomide in combination with R-ESHAP (LR-ESHAP) in patients with relapsed or refractory DLBCL. The phase 1b part of the trial has been completed and lenalidomide 10 mg/day was identified as the maximum tolerated dose (MTD) (Martín et al, Br J Haematol 2016; 173: 245-52). Here we present the preliminary results of the phase 2 (ClinicalTrials.gov Identifier: NCT02340936). Patients and methods: Eligible patients must be refractory to, or have relapsed following first-line treatment with rituximab in combination with an anthracycline-containing regimen and be eligible for autologous stem-cell transplantation (ASCT). Subjects received 3 cycles of lenalidomide 10 mg given on days 1 to 14 of every 21-day cycle, in combination with R-ESHAP salvage chemotherapy at standard doses (rituximab 375 mg/m2 day 1, etoposide 40 mg/m2 days 1-4, cisplatin 25 mg/m2 days 1-4, cytarabine 2000 mg/m2 day 5, and methylprednisolone 500 mg days 1-5). Responding patients received BEAM followed by ASCT. The primary endpoint was overall response rate (ORR) after 3 cycles of therapy. Secondary endpoints were complete remission (CR) rate, stem-cell mobilization activity, progression-free and overall survival, and toxicity. Results: Patient characteristics: 46 patients were included in the phase 2 analysis, of whom 12 were enrolled between January 2012 and March 2013, and had been given the MTD during phase 1; 34 were enrolled between January 2015 and November 2015. Median age was 58 (23-69) years, and 56.5% were male. Evaluable population per-protocol consisted of 44 patients because 2 patients were excluded during the first cycle due to withdrawal of consent and centralized diagnosis at relapse of lymphoblastic lymphoma, respectively. First-line treatment consisted of R-CHOP or similar in 38 patients, R-EPOCH in 3, VR-CAP in 1, and Burkitt lymphoma protocols in 2. Disease status at LR-ESHAP was: primary refractory disease in 67% of patients (partial response [PR] after first-line, n=13; and stable or progressive disease [

Description: Abstract 3654 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing affected patients a highly variable outcome. The improvement in survival gained with the addition of rituximab to CHOP chemotherapy (R-CHOP) led to re-define the international prognostic index (IPI). The new index, known as revised IPI (R-IPI), showed to be simpler as it groups the patients in only 3 risk groups. However, the effect of prior rituximab-therapy upon the usefulness and significance of previously recognized prognostic factors on patients relapsed or refractory and receiving subsequent treatment with rituximab plus chemotherapy in DLBCL remains unexplored. Biological parameters, including expression of Bcl-6, Bcl-2, p53 and MUM-1 have been described as IPI-independent prognostic factors. Objectives: The objective of this study was to evaluate the benefit of the R-IPI to predict the outcome of DLBCL patients at the relapse time following a front line treatment with chemotherapy and rituximab. We also aimed to establish in this population the relationship between immunohistochemical expression of biological parameters and outcome. Patients and methods: this was a multicentric, observational, post-authorization and cross-sectional study (ClinicalTrials.gov identifier: NCT01369784). Inclusion criteria were: patients with age ≥ 18 years with DLBCL refractory/relapsed after first line treatment with rituximab, with or without transplantation. Patients must have finished a rescue treatment including rituximab. Written informed consent was obtained from participants. When the data of the biopsies at diagnosis and relapse were available, immunohistochemical results of bcl-2, bcl-6, p53 and MUM-1 were obtained. Results: 152 patients were included (146 evaluables) with a median age of 58 years. At LDBCG diagnosis 48% had 〉 1 extranodal localization (29% had bone marrow disease), and 30% had ECOG 2 or greater. Eighty-one percent presented stages III or IV and 72% had elevated LDH. Three percent had very good prognosis R-IPI, 69% good prognosis R-IPI and 27% poor prognosis R-IPI. Most patients received R-CHOP as first line therapy. Overall response rate was 79% (40% complete remission). Relapse was confirmed with biopsy and histological study in 55 patients. At relapse 31% presented 〉 1 extranodal localization, 30% ECOG 2–4, 64% stages III-IV and 72% elevated LDH. R-IPI prognostic groups distribution at relapse were as follows: 8% very good, 75% good and 27% poor. R-ESHAP and R-GEMOX were the two more used rescue therapies resulting in 60% overall response rate (31% complete remission). R-IPI at relapse was significantly associated (p 〈 0,05) with overall response rate following R-chemotherapy rescue therapy. None of the immunohistochemical parameters analized correlated with rescue therapy results. Conclusions: This is the largest reported series analizing R-IPI in DLBCL at relapse/refractory in patients receiving R-chemotherapy. In this series of patients R-IPI calculated at the relapse time was the only prognostic factor capable of predicting the overall response to the second line of treatment. Thus R-IPI prognostic score is a simple and useful predictor for outcome in DLBCL at relapse/refractory Disclosures: No relevant conflicts of interest to declare.