ALBERT

Description: Introduction. The standard first-line treatment of young and fit mantle cell lymphoma (MCL) patients consists of a rituximab containing induction of CHOP and high dose ARA-C, followed by high dose consolidation and autologous stem cell transplant (ASCT). Thus far, almost all patients relapse after ASCT. Bortezomib is a proteasome inhibitor with activity in MCL. We investigated in a randomized phase II study whether there was any indication that maintenance therapy with bortezomib after ASCT could improve the outcome of treatment, measured as event free survival (EFS). Methods. Patients 18-65 years with newly diagnosed MCL were treated with 3 cycles of R-CHOP and 2 cycles of ARA-C (2 x 2 g/m2 iv d1-4) and rituximab (375 mg/m2, iv d11). Patients in PR or CR continued with ASCT after BEAM conditioning. Patients with a PR or CR after ASCT, with a neutrophil count 〉 0.5 x 109/l and platelets 〉 80 x 109/l were randomized between bortezomib and no further treatment. Bortezomib 1.3 mg/m2 iv was given once every two weeks, for 2 years, starting between 6 - 12 weeks after transplantation. Results . Between October 2007 and February 2012, 140 patients aged 34-66 years (median 57) were registered. Five patients were not eligible. The MIPI score was low, intermediate, high or unknown in 57%, 32%, 10% and 1% respectively. All eligible patients started induction treatment with R-CHOP. Two patients did not receive the first ARA-C cycle, because of progressive disease and physician decision. Hundred-fifteen patients (85%) received the BEAM and ASCT. Reasons to stop protocol treatment before ASCT were: progressive disease (PD) (n=6), inadequate stem cell harvest (n=3), excessive toxicity (n=3), other reasons (n=8). The response after ASCT was CR/CRu in 99 patients (86%), PR in 15 (13%), unknown in 1 (1%). Only 62 patients (45%), aged 34-65 years (median 56) were randomized between bortezomib maintenance and no further treatment. Two patients were randomized, but not eligible. Reasons for no randomization were: not eligible (n=30), patient refusal (n=14), excessive toxicity (n=2, and other reasons (n=7). In each treatment arm 30 patients were included. The patient characteristics were well balanced, except the MIPI score. In the no maintenance arm 21 patients (70%) had a low MIPI, compared to 15 patients (50%) in the bortezomib arm, and 6 (20%) versus 11 (37%) patients had an intermediate MIPI score. In both arms 3 patients (10%) had a high MIPI. Fifteen patients (50%) in the maintenance group continued bortezomib for 2 years. Reasons to stop earlier were excessive toxicity (n=6), PD/relapse (n=4), patients refusal (n=3) and other (n=2). The main adverse events during maintenance therapy were neurologic (CTC grade 2: 14%, grade 3: 4%), and infectious (grade 2: 11%, grade 3: 7%). Three patients developed a secondary malignancy: a basal cell carcinoma in the no maintenance group, a melanoma and a prostate carcinoma in the bortezomib group. With a median follow-up of the patients still alive of 50.9 months EFS at 4 years for all patients is 61%, and the overall survival (OS) 78%. The median follow-up of the randomized patients still alive is 42.9 months. The EFS at 4 years is 72% without maintenance versus 71% in the patients randomized for bortezomib maintenance. The OS at 4 years also shows no significant difference between the groups, 90% versus 93% respectively. Conclusion. There is no indication that bortezomib iv maintenance in a frequency of once every 2 weeks does improve the EFS of newly diagnosed MCL patients after intensive induction treatment with R-CHOP, double ARA-C and BEAM followed by ASCT. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Doorduijn: Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Off Label Use: bortezomib maintenance in MCL. Minnema:Celgene: Consultancy; Jansen Cilag: Consultancy; Amgen: Consultancy. Kersten:janssen: Honoraria, Research Funding; takeda millennium: Research Funding; roche: Honoraria, Research Funding. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Schipperus:Novartis: Consultancy. Zijlstra:Celgene: Consultancy; Roche: Consultancy.

Description: Purpose: For patients with limited stage diffuse large B-cell lymphoma (DLBCL) the overall survival (OS) in the pre-rituximab era was initially reported to be superior for abbreviated CHOP followed by radiotherapy compared to full course CHOP chemotherapy. At long term follow-up this benefit was lost. Rituximab(R) has increased the outcome of advanced stage patients, but the impact on limited stage DLBCL is less clear. Whether abbreviated R-CHOP followed by radiotherapy or full course R-CHOP is the treatment of choice remains controversial. Patients and methods: We performed an observational population-based cohort study of patients with stage I (E) DLBCL identified from 2 databases from the northern part of the Netherlands. Patients had been treated with abbreviated CHOP (3 cycles) followed by radiotherapy or full course CHOP (6-8 cycles). R was given to all patients after the drug became available in the Netherlands from 2004 onward. Primary endpoints were time to tumor progression (TTP) and OS Results: From 1984 until 2014 196 patients with stage I(E) were identified. Median follow-up was 53 and 110 months for patients treated with R and without R respectively Characteristics at diagnosis: median age 63 years (range 15-90), 20% ≥ 75 years; IPI-score 0-1: 88%; extranodal disease: 58%. Treatment: 190 patients completed at least 3 cycles of (R-)CHOP, 63% R and 37% without R . Full course (R-)CHOP was administered in 35% of patients. Patients with extranodal disease more often received full course (R-)CHOP (44%) compared to nodal disease (22%). Outcome: There were 32 relapses; 10 / 66 (15%) in full course (R-)CHOP and 22 / 124 (18%) in abbreviated (R-)CHOP followed by radiotherapy. Of the latter 19% were infield relapses. 5-year TTP and OS for the entire cohort were 83% (95%CI 78-89%) and 77% (95%CI 71-83%) respectively. In univariate analysis only IPI and age had significant impact on OS. Patients with an IPI-score of 0 had a hazard ratio (HR) of 0.50 compared to patients with an IPI-score ≥1 (95%CI 0.28-0.89, p 0.013). Patients ≤60 years and 60-75 years had a HR of 0.13 (95%CI 0.06-0.27, p 〈 0.01) and 0.34 (95%CI 0.18-0.63, p〈 0.01) respectively compared to patients ≥75 years for OS. No difference was found in OS between patients treated with abbreviated chemotherapy followed by radiotherapy or full course chemotherapy (HR 1.09, 95%CI 0.62-1.91, p 0.77); nor for treatment with or without R (HR 1.03, 95%CI 0.56-1.89, p 0.93). In univariate analysis only age ≤75 years was prognostic (HR 0.37 95%CI 0.17-0.84, p 0.017) for TTP. Of the relapses 25% occurred ≥ 3 years after treatment irrespective of rituximab exposure. Conclusions: In this large population-based analysis of patients with stage I(E) DLBCL no differences in OS and TTP were found between abbreviated R-CHOP followed by radiotherapy and full course R-CHOP. No clear benefit of R on OS, TTP and late relapses was found. With similar outcomes, toxicity should primarily determine the chose of treatment regimen. Disclosures Hoogendoorn: Gilead: Consultancy; Novartis: Consultancy.

Description: Mastocytosis is a hematopoietic disorder characterized by abnormal growth and accumulation of neoplastic mast cells (MC) in various organ systems. Using updated WHO criteria and the proposal of the consensus group, the disease can be divided into cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), smouldering SM (SSM), SM with an associated hematologic neoplasm (SM-AHN), aggressive SM (ASM), and mast cell leukemia (MCL). In adult patients with skin involvement but unknown/unavailable bone marrow (BM) studies, the provisional diagnosis ´mastocytosis in the skin (MIS)´ is appropriate. Although this classification has been validated repeatedly and is of prognostic significance, additional prognostic parameters have been identified in recent years (yrs). We have established a patient-registry in the ECNM where over 1,000 cases with confirmed mastocytosis are included. The aim of this study was to identify and validate new prognostic variables predicting survival in patients with mastocytosis and to prepare a simple prognostic scoring system applicable in daily practice. Using the data set of the ECNM registry we analyzed overall survival (OS) and event-free survival (EFS; i.e. until death or progression) in 1,088 patients with mastocytosis (median age: 45.7 yrs; range: 0.1-83.3 yrs, f:m ratio, 1:0.79), including CM (n=152), MIS (n=126), ISM (n=650), SSM (n=26), SM-AHN (n=89), ASM (n=35), and MCL (n=10). The median observation period was 3.5 yrs (75-25% percentile: 1.5-6.9 yrs, maximum 34.1 yrs). In the entire cohort, the median OS was not reached. The probability to be alive after 5, 10, and 20 yrs was 89%, 83%, and 70%, respectively. As expected, the WHO classification turned out to be of utmost predictive significance (Figure 1A; p70 yrs, PLT 70 yrs, PLT