ALBERT

Description: Cancer patients are often encouraged to receive seasonal influenza vaccination. The monoclonal antibody rituximab is widely used in treatment of non-Hodgkin lymphoma. This results in a prolonged depletion of normal B cells, which might impair humoral responses. The aim of the present study was to investigate whether lymphoma patients undergoing rituximab-containing treatment regimens or having received such regimens within the past 6 months were able to mount protective antibody responses to the influenza A(H1N1) 2009 virus vaccine Pandemrix during the 2009 “swine flu” pandemic. Contrary to the control group, where 82% responded adequately to the vaccine, none of the 67 patients achieved protective antibody titers, suggesting that lymphoma patients receiving rituximab-containing regimens might not benefit from this vaccine. It is important that doctors who care for such patients are aware that they may fail to respond not only to the influenza vaccine, but also to other common vaccines.

Description: Introduction: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of early central nervous system (CNS) progression is high. Here we present the final results from a Nordic phase II study, where dose-dense chemoimmunotherapy including early systemic CNS prophylaxis with high dose methotrexate (HD-Mtx), further intensified by intrathecally (IT) administered liposomal cytosine arabinoside (AraC), was given. Patients and methods: Inclusion criteria were age 18-65 years, de novo DLBCL or grade 3B follicular lymphoma without clinical, radiological or cytological signs of CNS involvement, age adjusted IPI 2-3, WHO performance score 0-3, and/or anatomical sites related to increased risk for CNS recurrence (e.g. testis, facial sinuses, orbita). Treatment consisted of two courses of HD-Mtx in combination with R-CHOP14, followed by four courses of R-CHOEP14 and one course of R-HD-AraC. Liposomal AraC was administered IT at courses 1, 3 and 5 (omitted during a period of production halt). Primary end points were failure free survival (FFS; disease progression, discontinuation of protocolled therapy due to toxicity, death from any cause) and CNS progression rate at 18 months. Among the secondary endpoints were the identification of biological risk factors for high risk disease and prognostic role of cerebrospinal fluid (CSF) cytology-/flow cytometry (FC)+for CNS recurrence. Results: Of the accrued 143 patients, 140 met the inclusion criteria and were evaluable for baseline characteristics and primary endpoints. Of these, 132 had a complete set of treatment data. The male/female ratio was 1.7 and the median age 56 years (range 20-64). The majority of the patients had DLBCL (96%), advanced clinical stage (93%), elevated LDH (91%), more than one extranodal site (73%), and B-symptoms (64%). A bulky lesion (〉10 cm) was present in 37% of the patients and 11 CSF samples (8%) were FC+. Most patients (n=127, 96%) received a full treatment schedule. Liposomal AraC was given to 81 (61%) and radiotherapy to 39 (30%) patients. Grade 4 infections were observed in 12% of the patients. The frequency of grade 3-4 mucositis as well as gastrointestinal toxicity was 20%, and of grade 3 arachnoiditis 2,5%. Three toxic deaths were observed. In addition, three patients developed AML/MDS and one PML. At the end of treatment, CR/CRu, PR and PD rates were 79%, 17% and 3%, respectively. Of the 120 patients who underwent PET-CT, 92 (77%) achieved a metabolic CR (Deauville score (DS) 1-3). Three patients had primary refractory disease. At a median follow-up of 30 months, additional 14 patients had relapsed, three of them in the CNS (only one had a pre-therapeutic FC+ CSF), and 15 had died. FFS, PFS, OS and CNS progression rates at 30 months were 80%, 83%, 90%, and 2.4%, respectively. PET positivity (DS 4-5) at the end of treatment (p=0.019) and BCL2 expression (p=0.049) were associated with increased risk of progression, whereas other factors, such as molecular subtype (GC versus non-GC), Ki-67 score (≥70%), aaIPI group (2 versus 3), number of extranodal sites, FC-based CSF positivity, and treatment with liposomal AraC did not seem to have significant impact on outcome. Conclusions: Safety profile and final outcome results of the Nordic CHIC trial indicate high response rates, favorable survival, low number of CNS recurrences and manageable toxicity as a result of this CNS targeted intensive therapy schedule. PET response at the end of therapy and selected biological factors identify patients at high risk of progression. Disclosures Leppa: Roche: Honoraria, Other: Travel expenses, Research Funding; Janssen: Research Funding; Bayer: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Other: Travel expenses; CTI Life Sciences: Honoraria; Merck: Other: Travel expenses. Joergensen:Amgen: Research Funding; Mundipharma: Research Funding. Mannisto:SOBI: Honoraria; Pfizer: Honoraria; Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses. Jerkeman:Gilead: Research Funding; Celgene: Research Funding; Mundipharma: Research Funding; Amgen: Research Funding; Janssen: Research Funding. Holte:Amgen: Research Funding; Mundipharma: Research Funding.

Description: Abstract 932 The Nordic Lymphoma Group has since 1996 conducted three consecutive phase II trials for front-line treatment of MCL patients ≤ 65 years of age. The first protocol (MCL1) 1996-2000 introduced high-dose chemotherapy with autologous stem cell support (unpurged or ex vivo purged) as consolidation after 4 cycles of intensified CHOP (maxi-CHOP). The results were disappointing, as the majority of patients relapsed. 1 Being in CR pre-transplant was the most important factor for outcome. Hence, in the second trial (MCL2) 2000-2006 induction therapy was intensified by adding high-dose Ara-C and rituximab to the regimen. Compared to MCL1 this led to significant improvement of event-free and overall survival, and the rate of PCR negative stem cell grafts and bone marrow samples.2 Again, responders in less than CR pre-transplant had a significantly poorer outcome. We therefore made a further intensification for the MCL3 study (2006-2009) by adding 90Y-Ibritumomab tiuxetan (Zevalin®) to the high-dose BEAC/BEAM to responders not in CR. Methods: As in the MCL1 and 2 studies newly diagnosed stage II-IV MCL patients ≤ 65 years were included. Induction treatment was identical to that of the MCL2 study with alternating cycles of maxi-CHOP-rituximab (3 cycles) and Ara-C-rituximab (3 cycles). Response evaluation was done after cycle 5. PET/CT was recommended, but could not influence the response evaluation, which was done according to the International Workshop criteria. Responders underwent in vivo purged harvest of stem cells after cycle 6 (Ara-C + 2 doses of rituximab). Patients in CRu or PR received a standard dose 90Y-Ibritumomab tiuxetan (0.4 mCi/kg) one week prior to the BEAM/BEAC, CR patients received BEAM/BEAC alone. Patients are followed by CT-scans, bone marrow and blood samples, including PCR for minimal residual disease or molecular relapse. For molecular relapse preemptive treatment with 4 standard doses of rituximab, as in the MCL2 study3, is given. Results: The planned accrual of 160 patients was reached in June 2009. The patient characteristics are similar to those of the MCL2 trial with a median age of 57 years (28-65), the majority male (80%) and in stage IV (89%) with bone marrow involvement (74%). The response rates pre-transplant so far compare favorably with data from MCL2 with 50% in CR, 18% in CRu, and 28% in PR. Only 4 out of 128 evaluable patients did not respond (3%) and there was one case (1%) of treatment-related mortality during induction therapy. While it is still too early to assess the impact of the 90Y-Ibritumomab tiuxetan on the progression-free survival, the side effects were similar to those of the MCL2 study including a treatment related mortality of 4%. Fifty-five patients in CRu or PR have so far been treated with 90Y-Ibritumomab tiuxetan, with no indication of any added toxicity. Only 12 out of 133 patients (10%) have not undergone transplant, 5 due to stem cell harvest failure, 3 due to toxicity and 4 due to non response to induction treatment. PET-scan prior to transplant was positive in 2% of CR patients, 20% of CRu patients and 54% of PR patients. Patients with a positive PET-scan pre-transplant had a 36% chance of achieving a molecular remission post-transplant, compared to 92% of cases with a negative PET-scan (p

Description: Introduction: In the Nordic Lymphoma Group trial NLG T-01, patients with newly diagnosed peripheral T-cell Lymphoma (PTCL) were treated with six courses of CHOEP (up to 60 yrs) or CHOP (61-67 yrs) followed by high-dose chemotherapy (BEAM) and autologous stem cell transplantation (ASCT). At 5 years median follow-up, the progression-free survival of the trial cohort was 44%. On this background, the NLG-T01 treatment strategy has become the recommended first-line treatment for younger fit patients in the Nordic countries and in the latest ESMO guidelines for PTCL. Despite this intensive approach with up-front ASCT a fraction of patients still relapses. In an attempt to find factors predictive for survival after up-front ASCT we aimed to analyze the impact of radiologic response at the first interim evaluation on long-term survival. Methods: All NLG T-01 patients (TrialP) with "nodal" PTCL, i.e. anaplastic large cell lymphoma, ALK-negative (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma not otherwise specified (PTCL NOS), that actually received the planned ASCT were included. Using national (Sweden and Denmark) or site-specific (Finland and Norway) registries, additional patients (RegP) who received the same treatment schedule, but off-protocol, were identified, and data for these patients was collected retrospectively. Overall survival (OS) was calculated from date of stem cell reinfusion until death from any cause. The first interim computed tomography (iCT) scan was performed after 3 cycles of chemotherapy. Response assessment in the NLG-T-01 trial was based on the 1999 International Working Group criteria for response, which allowed for complete remission unconfirmed and these patients have been grouped with CR in the present analysis. Progressive Disease (PD) was defined as increase of ≥25% of any lesion. Results: Altogether, 132 patients were included in the present study (TrialP n= 92; RegP n=40). The clinical characteristics are presented in the Table. The 5-year OS among all the patients was 58%. Response at iCT was CR, partial remission (PR) and SD in 44%, 53% and 3% respectively. Of the four patients with SD at iCT, all four patients attained PR after completing six cycles of chemotherapy prior to ASCT. Kaplan-Meier estimates for OS are illustrated in the Figure and the 5-year OS was identical, 61%, for patients in CR and PR but 0%for patients with SD. Using log-rank comparisons patients achieving SD at iCT had a significantly worse survival compared to patients with CR or PR (p=.01). Discussion: This study is to our knowledge the first to analyze whether interim treatment response can predict long-term OS in "nodal" PTCL patients treated with CHOEP or CHOP consolidated by up-front ASCT. Patients with SD after three cycles of chemotherapy had a very poor survival compared to patients with PR or CR. This was an expected finding, and it confirms the importance of chemo-sensitive disease as a necessary pre-requisite in order to benefit from up-front high-dose consolidation. Using CT, there was no survival difference between patients with CR or PR at the first interim evaluation. A larger cohort might reveal further differences in subgroups, particularly if PET/CT based remission evaluation should confirm itself as a useful tool also in nodal PTCL. At present our study indicates that failure to achieve PR after three cycles of CHOEP/CHOP identifies patients at high risk of relapse/progression that are in need of a different therapeutic strategy than continuing with CHOEP/CHOP towards an ASCT. Table Table. Figure Figure. Disclosures Mannisto: Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses; Pfizer: Honoraria; SOBI: Honoraria.

Description: Thalidomide was administered to 83 patients with myelodysplastic syndrome (MDS), starting at 100 mg by mouth daily and increasing to 400 mg as tolerated. Thirty-two patients stopped therapy before 12 weeks (minimum period for response evaluation), and 51 completed 12 weeks of therapy. International Working Group response criteria for MDS were used to evaluate responses. Intent-to-treat (ITT) analysis classified all off-study patients as nonresponders. Off-study patients belonged to a higher risk category (P = .002) and had a higher percentage of blasts in their pretherapy bone marrow than patients who completed 12 weeks of therapy (P = .003). No cytogenetic or complete responses were seen, but 16 patients showed hematologic improvement, with 10 previously transfusion-dependent patients becoming transfusion independent. Responders had lower pretherapy blasts (P = .016), a lower duration of pretherapy platelet transfusions (P = .013), and higher pretherapy platelets (P = .003). Among responders, 9 had refractory anemia (RA); 5 had RA with ringed sideroblasts; and 2 had RA with excess blasts. By ITT analysis, 19% of patients (16 of 83) responded, and when only evaluable patients were analyzed, 31% (16 of 51) responded. It was concluded that thalidomide, as a single agent, is effective in improving cytopenias of some MDS patients, especially those who present without excess blasts.