ALBERT

Description: Background: Aggressive non-Hodgkin lymphoma (aNHL) relapsing after high-dose therapy or, in not transplant-eligible patients, after 1st-line chemotherapy represents an unmet clinical need. Therefore, we aimed at evaluating a salvage combination regimen based on pixantrone, an aza-anthracenadione recently approved in Europe for patients with multiply relapsed aNHL. Etoposide and bendamustine were chosen as companion compounds due to available feasibility data in combination with anthracenadions, and a well-documented efficacy in salvage regimens for relapsed aNHL. Rituximab was added, if the relapse tumor biopsy was CD20+. Aim: The aim of the present analysis was to summarize the preliminary clinical experience with the PREBEN/PEBEN regimen gathered, on a compassionate need basis, at different European sites and representing the platform for a currently ongoing Nordic phase 1/2 trial in relapsed aNHL. Methods: The adopted schedule consisted of pixantrone 50 mg/m2 i.v. day 1+8, etoposide 100 mg i.v. day 1, bendamustine 90 mg i.v. day 1 with or without the addition of rituximab 375 mg/m2 i.v. day 1 (PREBEN/PEBEN). If feasible, each cycle was given at 3-weekly intervals for a maximum of 6 cycles. All patients were assessed for chemosensitivity with PET/CT, already after cycle 1 or 2. G-CSF support was applied and administered according to local practice. Results: A total of 30 heavily pre-treated patients (19 males and 11 females, age range 49-81 yrs; mean N of previous regimens: 3, range 1-7) with aNHL were treated according to the PREBEN/PEBEN schedule. Seventeen had diffuse large B-cell (DLBCL), six transformed indolent (tIND), and seven peripheral T-cell lymphoma (PTCL). All patients had intermediate or high risk IPI prior to start of salvage therapy. Eight patients (27%) had a complete metabolic response (CMR) and seven (23%) a partial one (PMR), resulting in an overall response rate (ORR) of 50%. Among the histological subtypes, the patients with DLBCL, PTCL and tIND had an ORR of 53% (CMR 35%), 57% (CMR 14%), and 33% (CMR in one out of two responders), respectively. Most responses were achieved early (prior to course nr. 4). Response durations ranged between 2 and 23+ months. Among the 17 patients with DLBCL, nine were frail, non transplant-eligible with relapsed disease, six had primary refractory lymphoma progressing through anthracycline-containing 1st line and platinum-containing salvage therapies, and two had relapses occurring after a post-transplant remission period. While most of the relapsed patients with DLBCL responded , i.e. seven (five CMR and two PMR) of the nine (78%) frail relapsed patients and one of the two (50%) patients with post-transplant relapses, only one out six (17%) primary refractory patients exhibited some chemosensitivity. Interestingly, four out of seven PTCL patients achieved a PMR or CMR allowing them to undergo non-myeloablative allogeneic transplant with subsequent sustained response durations. The treatment schedule was feasible and most patients received it on an out-patient basis. The most common grade 3-4 toxicity was of hematological type (mainly neutropenia and thrombocytopenia), occurring in 52% of the patients. Grade 3-4 infections were observed at a frequency of 21%. No septic deaths were recorded. A previously anthracycline exposed, heavily pre-treated 60-year old female PTCL patient developed symptomatic congestive heart failure effectively reversed by angiotensin converting enzyme inhibitors with normalization of the myocardial ejection fraction. One previously ibritumomab tiuxetan exposed, heavily pretreated patient with tIND developed acute myeloid leukemia with therapy-related cytogenetic features. Conclusions: The PREBEN/PEBEN salvage regimen was feasible in a heavily pre-treated cohort of elderly patients with high-risk aNHL. In individual patients it elicited substantial and durable responses early in the course of therapy. In some younger patients, it proved useful as bridging strategy to a non-myeloablative allogeneic transplant. A phase 1/2 study in relapsed (non-refractory) aNHL was launched in June 2016 (ClinicalTrial.gov identifier: NCT02678299; EudraCT number: 2015-000758-39) and is currently accruing (N=5 pr. Aug 1st, 2016). Disclosures Clausen: Takeda: Research Funding; Novartis: Other: Travel expences; Abbvie: Other: Travel expences. Leppa:Mundipharma: Research Funding; Roche: Honoraria, Other: Travel expenses, Research Funding; Bayer: Research Funding; Janssen: Research Funding; Takeda: Honoraria, Other: Travel expenses; CTI Life Sciences: Honoraria; Amgen: Research Funding; Merck: Other: Travel expenses. Willenbacher:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; European Commision: Research Funding. d'Amore:Servier: Honoraria, Other: Advisory Boards; CTI LIfe Sciences: Honoraria, Other: Advisory Boards.

Description: Background: 18F-FDG PET/CT is recommended in the initial staging of patients with classical Hodgkin lymphoma (cHL). Whereas focal 18F-FDG uptake in the skeleton is considered to represent bone involvement, it is still unclear whether diffusely increased 18F-FDG bone marrow uptake (BMU) indicates lymphoma infiltration or merely reflects a state of general inflammation. This retrospective study was therefore performed to study the relationship between pre-therapeutic (PET0) 18F-FDG BMU and the presence of focal bone lesions. Methods: A total of 139 patients (median age 44, range 8-83) referred to PET/CT between 2008 and 2014 for HL staging were included. All PET0 and post-therapeutic (PET2) images were reviewed and evidence of focal bone lesions was recorded (unifocal: ≤2 lesions, multifocal: 〉2 lesions). In addition, 18F-FDG uptake (SUVmax) was semiquantitatively measured in the vertebral bone marrow (SUVvertebra) and in the right lobe of the liver (SUVliver). BMU was calculated as SUVvertebra/SUVliver. The relationship between focal bone lesions on PET0 and BMU as well as age was subsequently analysed by logistic regression. Results: In total 30/139 (22 %) patients had focal bone lesions at initial staging (10 unifocal, 20 multifocal). BMU at initial presentation was generally increased in all patients when compared with the post-therapeutic PET/CT (PET0: 1.22 +/- 0.03 vs. PET2: 0.95 +/- 0.03, p

Description: Background: With currently available therapies, relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) after high-dose therapy or, in not transplant-eligible patients, after first-line chemotherapy represents an unequivocally unmet clinical need. Aim and Methods: Therefore, we aimed at evaluating a combination chemotherapy regimen based on pixantrone (Pix), a novel aza-anthracenadione recently approved by the European Medicines Agency in adult patients with multiply relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Etoposide and bendamustine were chosen as companion compounds due to available feasibility data in combination with Pix, as well as to their documented efficacy in salvage regimens in relapsed/refractory aggressive NHL and to a well-known feasibility profile when given alone or in combination. The monoclonal anti-CD20 antibody rituximab was added if tumor cells in the relapse biopsy specimen were CD20-positive. The adopted schedule consisted of Pixantrone 50 mg/m2 i.v. day 1+8, Etoposide 100 mg i.v. day 1, Bendamustine 90 mg i.v. day 1 with or without the addition of Rituximab 375 mg/m2 i.v. day 1 (PREBEN/PEBEN). If feasible, each cycle was given at 3-weekly intervals for a maximum of 6 cycles. All patients were assessed for chemosensitivity with PET/CT after cycle 1 or 2. G-CSF support was administered according to local guidelines. Results: A total of 8 evaluable patients with relapsed/refractory aggressive NHL were treated according to the PREBEN/PEBEN schedule. Abstract 5435. Table 1summarizes the clinico-pathological features of the patient cohort along with selected feasibility and efficacy parameters related to the PREBEN/PEBEN regimen (PET/CT status after 1 or 2 courses):Patient characteristicsPREBEN/PEBEN-related parametersPt #DxAgeSexCS at relapseN of prior Rx linesPrior TxN coursesTox grade 3-4Best responseDoR1DLBCL (ABC)70MIV3N6thrombocytopeniaCR*6 mo2DLBCL (ABC)49MIV3Y2-PD-3DLBCL (ABC)53MIV2N2neutropenic fevergoodPR4+ mo4DLBCL (ABC)64MIV2N2neutropenic fevergoodPR3+ mo5DLBCL (GCB)69FIV3N2-CR2+ mo6tFL62MIII3Y2neutropenic feverSD-7tCLL51FIV5Y2neutropenic feverPD-8PTCL-NOS57FIV2N6diarrhoeaCR4+ mo Baseline (pt#1) after 1 x PREBEN (pt#1) Figure 1 Figure 1. Figure 2 Figure 2. Conclusion: The PREBEN/PEBEN schedule is feasible (out-patient regimen) and in individual patients it elicits profound responses early in the course of therapy. A phase 1-2 study in relapsed/refractory DLBCL and PTCL is in preparation. Disclosures d'Amore: Amgen: Research Funding; Sanofi Aventis: Research Funding; CTI Life Sciences: Advisory board, Advisory board Other, Speakers Bureau; Mundipharma: Advisory board, Advisory board Other, Speakers Bureau; Takeda: Advisory board, Advisory board Other, Speakers Bureau; Kyowa Kirin Pharmaceuticals: Advisory board Other, Speakers Bureau; Roche: Research Funding.