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Herpes zoster (HZ) is a frequent complication after autologous stem cell transplantation (ASCT). The option of zoster prophylaxis with an antiviral drug is described in the literature, but there is no consensus on the drug and the dosage.We analyzed the records of 310 patients treated with ASCT who were controlled regularly regarding HZ inter alia for at least 24 months following ASCT. Since 01/2015 patients received prophylactic low-dose acyclovir (400 mg per day) during the first 12 months following discharge after ASCT (n = 107).Twenty percent of patients without this kind of prophylaxis and 2.8% of patients with prophylaxis developed HZ (p .001). No patient with this prophylaxis developed HZ in the first year after ASCT, 2.8% of patients in the second year after ASCT. A prognostic factor was the kind of diagnosis: 30% of lymphoma patients and 14% of myeloma patients developed HZ in the first 24 months after ASCT without prophylaxis, but only 6.3% and 0% of patients with prophylaxis, respectively. Neither an increase of HZ cases following prophylaxis nor acyclovir refractory HZ cases were observed.Zoster prophylaxis with low-dose acyclovir over 12 months after ASCT is effective and well tolerated.

BACKGROUND Autologous haematopoietic stem-cell transplantation (HSCT) in first remission is the current standard treatment in fit patients with mantle cell lymphoma. In this long-term follow-up study, we aimed to evaluate the efficacy of autologous HSCT versus interferon alfa maintenance after chemotherapy without or with rituximab in patients with primary advanced-stage mantle cell lymphoma. METHODS We did a post-hoc, long-term analysis of an open-label, multicentre, randomised, phase 3 trial done in 121 participating hospitals or practices across six European countries. Patients who were aged 18-65 years with previously untreated stage III-IV mantle cell lymphoma and an ECOG performance score of 0-2 were eligible for participation. Patients were randomly assigned (1:1) to receive either myeloablative radiochemotherapy (fractionated total body irradiation with 12 Gy/day 6-4 days before autologous HSCT and cyclophosphamide 60 mg/kg per day intravenously 3-2 days before autologous HSCT) followed by autologous HSCT (the autologous HSCT group) or interferon alfa maintenance (the interferon alfa maintenance group; 6 × 106 IU three times a week subcutaneously until progression) after completion of CHOP-like induction therapy (cyclophosphamide 750 mg/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, vincristine 1·4 mg/m2 maximum 2 mg intravenously on day 1, and prednisone 100 mg/m2 orally on days 1-5; repeated every 21 days for up to 6 cycles) without or with rituximab (375 mg/m2 intravenously on day 0 or 1 of each cycle; R-CHOP). The primary outcome was progression-free survival from end of induction until progression or death among patients who had a remission and the secondary outcome was overall survival from the end of induction until death from any cause. We did comparisons of progression-free survival and overall survival according to the intention-to-treat principle between both groups among responding patients and explored efficacy in subgroups according to induction treatment without or with rituximab. Hazard ratios (HRs) were adjusted for the mantle cell lymphoma international prognostic index (MIPI) numerical score, and in the total group also for rituximab use (adjusted HR aHR). This trial was started before preregistration was implemented and is therefore not registered, recruitment is closed, and this is the final evaluation. FINDINGS Between Sept 30, 1996, and July 1, 2004, 269 patients were randomly assigned to receive either autologous HSCT or interferon alfa maintenance therapy. The median follow-up was 14 years (IQR 10-16), with the intention-to-treat population consisting of 174 patients (93 53{\%} in the autologous HSCT group and 81 47{\%} in the interferon alfa maintenance group) who responded to induction therapy. The median age was 55 years (IQR 47-60), and R-CHOP was used in 68 (39{\%}) of 174 patients. The median progression-free survival was 3·3 years (95{\%} CI 2·5-4·3) in the autologous HSCT group versus 1·5 years (1·2-2·0) in the interferon alfa maintenance group (log-rank p{\textless}0·0001; aHR 0·50 95{\%} CI 0·36-0·69). The median overall survival was 7·5 years (95{\%} CI 5·7-12·0) in the autologous HSCT group versus 4·8 years (4·0-6·6) in the interferon alfa maintenance group (log-rank p=0·019; aHR 0·66 95{\%} CI 0·46-0·95). For patients treated without rituximab, the progression-free survival adjusted HR for autologous HSCT versus interferon alfa was 0·40 (0·26-0·61), in comparison to 0·72 (0·42-1·24) for patients treated with rituximab. For overall survival, the adjusted hazard ratio for HSCT versus interferon alfa was 0·52 (0·33-0·82) without rituximab and 1·05 (0·55-1·99) for patients who received rituximab. INTERPRETATION Our results confirm the long-term efficacy of autologous HSCT to treat mantle cell lymphoma established in the pre-rituximab era. The suggested reduced efficacy after immunochemotherapy supports the need for its re-evaluation now that antibody maintenance, high-dose cytarabine, and targeted treatments have changed the standard of care for patients with mantle cell lymphoma. FUNDING Deutsche Krebshilfe, the European Community, and the Bundesministerium f{\"u}r Bildung und Forschung, Kompetenznetz Maligne Lymphome.

OBJECTIVE To contribute data on long-term outcome and potential curative impact of ASCT in FL, especially following HDT with the BEAM protocol (BCNU, etoposide, cytarabine and melphalan), given very limited data on this topic in the literature. PATIENTS AND METHODS Patients with FL (n = 76) were treated in our institution with HDT and ASCT. In the case of long-term remission (≥8 years), peripheral blood was tested for minimal residual disease by t(14;18)- and IGH-PCR, including the last follow-up. RESULTS 10-year overall survival, progression-free survival, and freedom from progression (FFP) after first-line ASCT (n = 20) were 80%, 60%, and 69%, after second-line ASCT (n = 48, following BEAM) 66%, 38%, and 41%, after third/fourth-line ASCT (n = 8) 33%, 25%, and 25%, respectively. Prognostic factors for FFP were treatment line and FLIPI (Follicular Lymphoma International Prognostic Index). 10-year FFP for second-line ASCT and low-risk FLIPI at relapse was 69%, intermediate-risk 28%, and high-risk 25% (P

Summary Background R-MegaCHOEP was the first phase 3 study comparing high-dose chemotherapy plus rituximab followed by autologous haematopoietic stem-cell transplantation (HSCT) with conventional chemotherapy plus rituximab in first-line therapy for patients aged 60 years or younger with high-risk aggressive B-cell lymphoma. Little is known about the long-term outcomes of these patients. We aimed to evaluate the long-term efficacy and safety of conventional chemotherapy versus high-dose chemotherapy after 10 years of follow-up in the R-MegaCHOEP trial. Methods In this open-label, randomised, phase 3 trial done across 61 centres in Germany, patients aged 18–60 years with newly diagnosed, high-risk (age-adjusted International Prognostic Index [IPI] 2 or 3) aggressive B-cell lymphoma were randomly assigned (1:1, using Pocock minimisation) to eight cycles of conventional chemotherapy (cyclosphosphamide, doxorubicin, vincristine, etoposide, and prednisolone) plus rituximab (R-CHOEP-14) or four cycles of high-dose chemotherapy plus rituximab followed by autologous HSCT (R-MegaCHOEP). The trial was unmasked. Patients were stratified by age-adjusted IPI factors, presence of bulky disease (tumour mass ≥7·5 cm diameter), and treatment centre. The primary endpoint was event-free survival, analysed here 10 years after randomisation. 10-year overall survival, progression-free survival, conditional survival, relapse patterns, secondary malignancies, and molecular characteristics were also analysed. All analyses were done on the intention-to-treat population. This trial is registered with ClinicalTrials.gov , NCT00129090 . Findings Between March 3, 2003, and April 7, 2009, 275 patients were randomly assigned to R-CHOEP-14 (n=136) or R-MegaCHOEP (n=139). 130 patients in the R-CHOEP-14 group and 132 patients in the R-MegaCHOEP group were included in the intention-to-treat population. After a median follow-up of 9·3 years (IQR 5·1–11·1), 10-year event-free survival was 51% (95% CI 42–61) in the R-MegaCHOEP group and 57% (47–67) in the R-CHOEP-14 group (adjusted hazard ratio [HR] 1·3 [95% CI 0·9–1·8], p=0·23). 10-year progression-free survival was 59% (50–68) in the R-MegaCHOEP group and 60% (51–70) in the R-CHOEP-14 group (adjusted HR 1·1 [0·7–1·7], p=0·64). 10-year overall survival was 66% (57–76) in the R-MegaCHOEP group and 72% (63–81) in the R-CHOEP-14 group (adjusted HR 1·3 [0·8–2·1], p=0·26). Relapse occurred in 30 (16% [95% CI 11–22]) of 190 patients who had complete remission or unconfirmed complete remission; 17 (17%) of 100 patients in the R-CHOEP-14 group and 13 (14%) of 90 patients in the R-MegaCHOEP group. Seven (23%) of 30 patients had low-grade histology at relapse and had better outcomes compared with patients who relapsed with aggressive histologies. Lymphoma affected the CNS in 18 (28%) of 64 patients with treatment failure. 22 secondary malignancies were reported in the intention-to-treat population; in 12 (9%) of 127 patients in the R-CHOEP-14 group and ten (8%) of 126 patients in the R-MegaCHOEP group. Interpretation Event-free survival and overall survival were similar between groups after 10 years of follow-up; outcomes were not improved in the R-MegaCHOEP group by high-dose chemotherapy and autologous HSCT. Patients who relapsed with aggressive histology showed a high incidence of CNS involvement and poor prognosis. For these patients, novel therapies are greatly warranted. Funding Deutsche Krebshilfe (German Cancer Aid).

We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P = 0.002; HR 0.548 (95% CI 0.38-0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.

This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n = 199). Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months median follow-up, median PFS with auto/allo versus tandem autoSCT was 34.5 versus 21.8 months (P = 0.003; adjusted hazard ratio 0.55, 95% confidence interval 0.36–0.84). Median overall survival (OS) was 70.2 versus 71.8 months (P = 0.856). Two-year non-relapse mortality with auto/allo versus tandem autoSCT was 14.3% versus 4.1% (P = 0.008). In patients harboring both del13q and del17p, median PFS and OS were 37.5 and 61.5 months with auto/allo (n = 19) versus 6.1 and 23.4 months with tandem autoSCT (n = 6) (P = 0.0002 and 0.032). Our findings suggest that auto/alloSCT significantly extends PFS versus tandem autoSCT in del13q MM, and indicate some survival benefit for first-line alloSCT in high-risk MM.

OBJECTIVE A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed. METHODS Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation. RESULTS Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P = .0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non-existent in the bortezomib consolidation arm but pronounced in the observation arm (P = .0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P = .0569). CONCLUSIONS Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards.

The prognosis of an early relapse of diffuse large B-cell lymphoma (DLBCL) appears to be poor following autologous stem cell transplantation (ASCT). The aim of this study is to contribute data to the open question on whether additional radiotherapy can improve the outcome. Forty-eight patients with an early relapse (median 4 months after the end of initial immunochemotherapy, range 1–11) of DLBCL have been treated in our institution with high-dose therapy (usually the BEAM protocol) and ASCT since 2008 (median age 61 years, range 28–73). Twenty-three patients received ASCT in a second treatment line, 25 in a third line (19 refractory to second-line salvage therapy, 5 after second relapse). Fifteen of these 48 patients received radiotherapy (36–50 Gy, median 40) of residual masses after ASCT. Three-year overall survival (OS) and progression-free survival (PFS) after second-line ASCT were 61 and 57%, after third-line ASCT 47 and 44%, respectively, without significant differences. A prognostic factor was the International Prognostic Index (IPI) at the start of salvage therapy. Three-year OS and PFS in low-risk patients were 69 and 69%, in low-intermediate-risk 63 and 53%, and in high-intermediate-risk 23 and 23%, respectively (p = 0.033). Twenty-three patients achieved a sustained complete remission (13–146 months, median 62). Sustained long-term remissions can be achieved in patients with early relapse of DLBCL following ASCT in a second or third treatment line, particularly in patients with low- and low-intermediate-risk IPI, following radiotherapy of residual disease after ASCT. Further investigations are required to clarify which patients need an alternative therapy (potentially CAR T‑cells or allogeneic transplantation).

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter–related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156).

INTRODUCTION: Mantle cell lymphoma (MCL) is a distinct subtype of lymphoma and is characterized by an aggressive clinical course in the majority of cases. In older patients, commonly used induction regimens are either anthracycline-containing CHOP-like regimens or bendamustine, both in combination with rituximab, followed by rituximab maintenance [Dreyling, 2017]. Data on efficacy and safety of rituximab in MCL are mainly derived from the randomized GLSG2000 trial, showing higher remission rates and longer FFS with R-CHOP vs. CHOP, but no significant differences in PFS in remission and OS due to limited statistical power [Lenz, 2005]. We now performed a long-term ITT analysis of CHOP vs. R-CHOP from all GLSG2000 patients pooled with the CHOP patients of the preceding GLSG1996 trial. METHODS: Of GLSG2000 and GLSG1996 trials, patients with advanced stage, previously untreated MCL, prospectively assigned to chemotherapy only (CHOP) or the combination with rituximab (R-CHOP), were included in this pooled analysis. Primary endpoints of this evaluation were FFS and OS, tested hierarchically. Secondary endpoints included PFS in first remission, OS after first treatment failure and rate of secondary malignancies. Exploratory subgroup analyses for FFS and OS were performed according to sex (female, male), MIPI (low, intermediate, high), Ki-67 ( RESULTS: Between 1996 and 2006, 385 MCL patients were included to receive either CHOP (n=201) or R-CHOP (n=184). Key patient characteristics were well balanced: Median age was 61 (37-86) versus 62 (35-84) years, 72 and 79% were male, median MIPI score was 5.78 (4.52-9.18, n=197) versus 5.80 (4.59-8.60 n=175), Ki67 ≥ 30% was seen in 17% (n=115) versus 17% (n=96) and blastoid morphology was seen in 8% (n=61) versus 8% (n=60) of patients treated with CHOP and R-CHOP, respectively. ASCT consolidation was done in 15% (n=31) and 21% (n=39) of CHOP and R-CHOP patients, respectively (p=0.15). Median FFS was 1.36 (95% CI: 1.18 - 1.66) vs. 2.07 (1.78 - 2.65) years, adjusted HR 0.62 (0.50 - 0.77), p Regarding long term toxicity, the rate of secondary malignancies after 10 years was 0,5 and 3,9% for hematological and 7 and 8% for non-hematological malignancies for CHOP and R-CHOP, respectively. In subgroup analyses, an efficacy of rituximab was seen across all MCL risk groups: HRs for FFS were 0.58 (95 % CI: 0.36 - 0.94) for MIPI high, 0.59 (0.41 - 0.84) for MIPI intermediate and 0.69 (0.49 - 0.97) for MIPI low (interaction p=0.80 for MIPI high vs. low; interaction p=0.50 for MIPI intermediate vs. low); aHRs for Ki67 ≥ 30% vs < 30% were 0.51 (0.25 - 1.05) vs. 0.73 (0.53 - 0.99; interaction p=0.056) and for blastoid vs. non-blastoid morphology 0.19 (0.04 - 1.03) vs. 0.77 (0.52 - 1.14; interaction p=0.19), respectively. CONCLUSION: We present mature results of a pooled MCL cohort, now demonstrating a statistically significantly prolonged OS for the combined immuno-chemotherapy confirming the current standard of care in first line treatment of MCL. Figure 1 Figure 1. Disclosures Bittenbring: Gilead: Consultancy; Pfizer: Consultancy. Hübel: Gilead: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Celgene: Consultancy; EUSA: Consultancy, Speakers Bureau. Schmidt: Novartis: Consultancy, Honoraria, Other: Travel support; Kite/Gilead: Consultancy, Honoraria, Other: Travel support, Research Funding; Takeda: Consultancy, Other: Travel support; BMS: Consultancy, Other: Travel support; Janssen: Other: Travel support. Glass: Kite: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Riemser: Research Funding; Novartis: Consultancy; Helios Klinik Berlin-Buch: Current Employment; BMS: Consultancy. Hüttmann: Gilead: Honoraria; Celgene: Honoraria; Lead Discovery Center GmbH: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Klapper: Takeda: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Regeneron: Consultancy, Research Funding; Amgen: Research Funding. Hiddemann: Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Unterhalt: Roche: Research Funding. Dreyling: Genmab: Consultancy; BeiGene: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Abbvie: Research Funding; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau.

Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively. BEAM, Z-BEAM and R-BEAM groups were well balanced for age, time from diagnosis to ASCT and disease status at ASCT. The cumulative incidences of relapse (IR) at 2 years were 34, 34 and 32% for Z-BEAM, R-BEAM and BEAM, respectively. By multivariate analysis, there were no significant differences with Z-BEAM or R-BEAM compared with BEAM for IR, non-relapse mortality, event-free survival or overall survival. With the caveat that the limitations of registry analyses have to be taken into account, this study does not support adding radioimmunotherapy or R to BEAM in ASCT for relapsed FL. However, we cannot rule out the existence a particular subset of patients who could benefit from Z-BEAM conditioning that cannot be identified in our series, and this should be tested in a randomized trial.Bone Marrow Transplantation advance online publication, 22 May 2017; doi:10.1038/bmt.2017.88.

Introduction:Considering the increasing numbers of lymphoma patients (pts) surviving long-term, late effects of current treatment strategies such as secondary (sec) malignancies gain increasing importance. Many treatment regimens used in pts with lymphoma (R-CHOEP, DA-EPOCH-R, BEACOPP) include etoposide, a cytotoxic agent reported to increase sec leukemias. In order to further investigate the role of etoposide in inducing sec malignancies in pts with aggressive lymphoma we analyzed the R-MegaCHOEP trial (Schmitz et al., Lancet Oncology 2012) where young, high-risk pts with aggressive B-cell lymphomas had received R-CHOEP or R-MegaCHOEP, a regimen containing very high doses of etoposide (4g/m2). We compared rates of secondary tumors to incidences found in young patients treated with R-CHOP only. Methods:We analyzed 1536 pts aged 18-60 years with aggressive B-cell lymphoma treated in the prospective phase 3 trials FLYER (NCT00278421; n=588, median observation time (OT)=66 months), UNFOLDER (NCT00278408; n=695, median OT=72 months) and MegaCHOEP (NCT00129090; n=253, median OT=112 months) to compare the cumulative incidences of sec neoplasms. We performed a competing risk analysis for time from randomization to occurrence of sec malignancy (myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or other) according to first-line therapy with R-CHOP (n=1283) vs. R-CHOEP (n=127) vs. R-MegaCHOEP (n=126). We used a cause-specific hazard model adjusted for gender, age (>50 vs. Results:Adjusting for competing events, we found sec MDS/AML in 0.3% of pts treated with R-CHOP, in 1% of pts treated with R-CHOEP and in 2% of pts following treatment with R-MegaCHOEP. Cause-specific hazard ratios showed a trend for increased risk for sec AML following R-MegaCHOEP in comparison to R-CHOP (HR 5.2, 95%CI (1.0; 27.5), p=0.052) while R-CHOEP did not significantly increase the incidence of sec AML (HR 1.4, 95%CI (0.1; 14.0), p=0.777). Male gender and age >50 years showed a trend for increasing sec AML. We found very similar incidences of sec solid tumors (not MDS/AML) affecting 4% of pts treated with R-CHOP or R-MegaCHOEP and 6% of pts following R-CHOEP regimen. The only factor significantly increasing the risk of sec solid tumors was age >50 years (HR 2.6, 95%CI (1.5; 4.3), p Conclusions:This analysis shows that sec malignancies represent rare events in younger patients with aggressive B-cell lymphoma, even after extreme dose-escalation of etoposide. Compared to standard R-CHOP, 8 cycles of R-CHOEP were not associated with increased risk of sec AML or solid tumors thus remaining an attractive first-line treatment for young high-risk pts with DLBCL. Disclosures Haenel: Amgen, Novartis, Roche, Celgene, Takeda, Bayer:Honoraria.Truemper:Janssen:Consultancy;Mundipharma:Research Funding;Nordic Nanovector:Consultancy;Roche:Research Funding;Seattle Genetics:Research Funding;Takeda Europe:Consultancy, Research Funding.Held:MSD:Consultancy;Acrotech, Spectrum:Research Funding;Amgen:Research Funding;BMS:Consultancy, Other: Travel Grants, Research Funding;Roche:Consultancy, Other: travel grants, Research Funding.Borchmann:Bristol Myers Squibb:Research Funding;Takeda:Research Funding.Dreyling:Celgene:Consultancy, Research Funding, Speakers Bureau;Roche:Consultancy, Research Funding, Speakers Bureau;Beigene:Consultancy;Janssen:Consultancy, Research Funding, Speakers Bureau;Novartis:Consultancy;Abbvie:Research Funding;Astra Zeneca:Consultancy;Bayer:Consultancy, Speakers Bureau;Gilead:Consultancy, Research Funding, Speakers Bureau.Viardot:Roche:Honoraria, Other: advisory board;Kite/Gilead:Honoraria, Other: advisory board;Novartis:Honoraria, Other: advisory board;Amgen:Honoraria, Other: advisory board.Kroschinsky:Riemsser:Research Funding;Roche:Consultancy, Honoraria, Other: Support of parent study and funding of editorial support;Gilead:Consultancy;BMS/Celgene:Consultancy, Honoraria;Sandoz:Research Funding.Ott:NIH:Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America..Lenz:Bayer:Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen:Consultancy, Honoraria, Research Funding, Speakers Bureau;Novartis:Consultancy;Gilead:Consultancy, Honoraria, Research Funding, Speakers Bureau;AQUINOX:Research Funding;AstraZeneca:Consultancy, Honoraria, Research Funding;Celgene:Consultancy, Honoraria, Speakers Bureau;Verastem:Research Funding;Morphosys:Consultancy, Honoraria, Research Funding;Roche:Consultancy, Honoraria, Research Funding, Speakers Bureau;Agios:Research Funding;BMS:Consultancy.Schmitz:Riemser:Honoraria;Takeda:Honoraria;Janssen:Research Funding;Bristol-Myers Squibb:Current equity holder in publicly-traded company.

Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex, VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was &gt, 30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR &lt, 45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p &lt, 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.

Summary Background Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. Methods This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II–IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II–IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Findings Of 497 patients (median age 55 years [IQR 49–60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6·1 years (95% CI 5·4–6·4), time to treatment failure was significantly longer in the cytarabine group (median 9·1 years [95% CI 6·3–not reached], 5 year rate 65% [95% CI 57–71]) than in the control group (3·9 years [3·2–4·4], 40% [33–46]; hazard ratio 0·56; p=0·038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241m vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of ASCT-related deaths was similar (eight [3·4%]) in both groups. Interpretation Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma. Funding European Commission, Lymphoma Research Foundation, and Roche.

Objective A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT). Methods Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively). Following induction and ASCT, patients were randomized 1:1 to four 35-day cycles of bortezomib consolidation (1.6 mg/m2 IV on days 1, 8, 15, 22) or observation only. Results Median PFS with bortezomib consolidation vs observation was 33.6 vs 29.0 months (P = 0.3599) in patients aged 18-60 years (n = 202), and 33.4 vs 26.4 months (P = 0.0073) in patients aged 61-75 years (n = 155), respectively. Bortezomib consolidation post-ASCT appeared to equalize outcomes between older and younger patients who received prior treatment of differing intensity. This suggests that the effect of consolidation may be relative and may depend on the composition and intensity of induction and high-dose therapy. Conclusion Older patients receiving less intensive prior treatment could experience a larger PFS benefit from bortezomib consolidation.

8521 Background: High-dose chemotherapy (HDT) followed by autologous stem cell transplant (SCT) remains a standard of care in patients (pts) with newly diagnosed (ND) multiple myeloma (MM). While lenalidomide (R) maintenance is acknowledged to improve outcomes, intensified consolidation (such as tandem-SCT) has yielded conflicting results. Allogeneic (allo) SCT holds the promise of curative potential at the cost of higher treatment-related mortality (TRM). In a previous phase 2 study, we showed a very low TRM rate (6.1%) and feasibility of 12 months (mos) of R maintenance (maint), with auto/allo SCT after R/adriamycin/dexamethasone (RAD). This prompted us to compare, on a randomized rather than a “biological assignment” basis, a second auto- versus (vs) an allo-SCT in pts with an unfavorable prognosis. Methods: The current protocol (DSMM XIV, NCT01685814) was set up according to a double 2x2-factorial design. Post-induction (PInd) CR rate was the efficacy endpoint for the comparison of RAD vs bortezomib (V)/RD (VRD; 3 cycles each). If pts had achieved >VGPR to HDT, a second randomization (2ndR) compared immediate R maint (arm A2) with a second auto-SCT (B2). In case of < VGPR, pts were randomized between a second auto- (C2) and allo-SCT (D2). Planned R maint. duration was 36 mos, except after allo (12 mos). Results: Between 05/2012-06/2016, 476 pts were randomized and 469 received at least one dose of study drug. Pts’ median age was 55 (range, 32–65) years. 11.3% of pts had FISH del17p; 11.6% had t(4;14); and 4.4% had t(14;16). PInd CR rate was 11.8% (90% CI, 7.9%-16.3%) with RAD and 13.0% (90% CI, 8.9-18.0) with VRD (P = .697). 382 pts underwent R2 with 279 pts. (73%) in >VGPR and 103 (27%) in < VGPR, respectively. Median duration of R maint (N = 298) was 21.2 mos for A2, 23.1 mos for B2, 27.4 mos for C2, and 11.0 mos. for D2. At a median follow-up of 40.2 (0.5-87.0) months, median PFS from first randomization with RAD was 41.7 (95% CI, 35.4-48.5) mos vs. 53.7 (95% CI, 46.2-63.1) mos with VRD (P = .0439). Median PFS from 2ndR was 38.7 (95% CI, 30.3-47.3) mos for the 181 RAD vs. 50.7 (95% CI, 44.4-64.9) mos for the 201 VRD pts (P = .0126). Median overall survival (OS) cannot be estimated. With 47 deceased RAD vs 36 VRD pts, HR was .671 (95% CI, .435-1.037; P = .0703). Conclusions: In this study, median PFS benefit was 12 mos in favor of VRD vs. RAD despite comparable PInd CR. We show for the first time a len-PI to be superior to a len-chemo triplet, confirmed with positive OS trends. 3-year PFS for all consolidation arms will be presented. Clinical trial information: NCT01685814 .

Background: Six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) or R-CHOP-like chemotherapy are the standard treatment for aggressive B-cell non-Hodgkin's lymphoma. We hypothesized that four cycles of CHOP plus six applications of rituximab (4x R-CHOP+2xR) are non-inferior to six cycles of R-CHOP in a population with favorable prognosis. Methods: We randomized patients 18 to 60 years of age, stage I-II disease, normal serum lactate dehydrogenase concentration, good ECOG performance status 0-1, without bulky disease (maximal tumor diameter

Background: Allogeneic (allo) following autologous (auto) stem-cell transplantation (SCT) has yielded conflicting results in newly diagnosed multiple myeloma (MM). In alloSCT, information is lacking regarding the impact of cytogenetic features except chromosome 13q deletion (del13q). Methods: This phase 3 trial compared tandem autoSCT versus autoSCT followed by reduced-intensity conditioning alloSCT (auto/alloSCT) in del13q MM. The availability/absence of a human leukocyte antigen-matched related or matched unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intent-to-treat population (n=199). Findings: Auto/alloSCT was performed in 126 patients; 74 received MUD allografts. After 91 months' median follow-up (range 2-143 months), median PFS with auto/allo versus tandem autoSCT was 34·5 versus 21.8 months (p=0·003; adjusted hazard ratio 0·55, 95% confidence interval [CI] 0·36-0·84). Median overall survival (OS) was 70.2 versus 71.8 months (p=0.856). Two-year non-relapse mortality (NRM) with auto/allo versus tandem autoSCT was 14·3% versus 4·1% (p=0·008). In patients harbouring both del13q and deletion of chromosome 17p, median PFS and OS were 37·5 and 61·5 months with auto/allo (n=19) versus 6·1 and 23·4 months with tandem autoSCT (n=6) (p=0·0002 and 0·032). Interpretation: Auto/alloSCT significantly extends PFS versus tandem autoSCT in patients with del13q MM. We believe this to be the first MM study demonstrating that MUD alloSCT can be performed with reasonable NRM. Furthermore, our data suggest some survival benefit for first-line alloSCT in high-risk MM. Funding: The trial was sponsored by Wurzburg University, Wurzburg, Germany. Declaration of Interest: MH reports personal fees from Amgen, Celgene, Janssen, Bristol-Myers Squibb, and Takeda. GH reports personal fees from Janssen, Roche, AbbVie, Gilead, Novartis, MorphoSys, and Celgene; and grants from Roche, Pfizer, and Celgene. SM reports non-financial support from EBMT/EHA, IACH, Celgene, Miltenyi, KIADIS, Bellicum, DGHO, Jazz Pharma, and ISCT; and personal fees from Celgene, Miltenyi, KIADIS, Bellicum, and Jazz Pharma. GM reports personal fees from Gilead, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, and Merck-Serono; and non-financial support from Janssen-Cilag. LK reports honoraria for presentation at “MedIpdate” (OnkoUpdate, IntemistenUpdate, PraxisUpdate) and at “Medizin Aktuell”. Amgen and Celgene are sponsors of the “Biannual International Stem Cell Conference, Tubingen, Germany): Scientific chairman: LK. HE reports grants, personal fees, and other (advisory board) from Janssen, Celgene, Amgen, BristolMyers Squibb, Novartis, and Takeda. All other authors declare no competing interests. Ethical Approval: The trial protocol was approved by the Wurzburg University ethics committee. All patients provided written informed consent prior to trial entry, and all procedures were conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidelines for Good Clinical Practice.

Item does not contain fulltext Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in relapsed HL. In order to assess the prognostic relevance of DHAP dose density, we performed a retrospective multivariate analysis of the HDR2 trial (N = 266). In addition to four risk factors (early or multiple relapse, stage IV disease or anemia at relapse, and grade IV hematotoxicity during the first cycle of DHAP) a delayed start of the second cycle of DHAP > day 22 predicted a significantly poorer progression-free survival (PFS, p = 0.0356) and overall survival (OS, p = 0.0025). In conclusion, our analysis strongly suggests that dose density of DHAP has a relevant impact on the outcome of relapsed HL patients.

Patients with follicular lymphoma (FL) and progression of disease (POD) within 24 months after frontline treatment (POD24) have poor overall survival (OS). The optimal salvage treatment for these patients is unknown. We assessed the role of high-dose therapy and autologous stem cell transplantation (ASCT) in transplant-eligible patients. We analyzed 162 patients with advanced-stage FL who had received frontline treatment within the GLSG1996 or GLSG2000 trials. All patients had POD at age ≤ 65 years and had not received a prior transplant. Second-line treatment was not specified by study protocols. Survival was calculated from time of second-line treatment. Eighteen patients (11%) progressed (n = 16) or died (n = 2) during cytoreductive second-line treatment (considered "cytoreduction failure"); none received ASCT, and their median second-line OS was1 year. A total of 113 patients had POD24 (70%), whereas 49 had POD after 24 months (30%). Sixty-three patients without cytoreduction failure received ASCT (39%), and 81 received no transplant (50%). In patients with POD24, a significant survival benefit was associated with ASCT with a 5-year second-line progression-free survival for ASCT versus no transplant of 51% versus 19% (hazard ratio, .38; 95% confidence interval, .24 to .62; P .0001) and a 5-year second-line OS of 77% versus 59% (hazard ratio, .54, 95% confidence interval, .30 to .95; P= .031). Thus, ASCT is an effective treatment option for transplant-eligible patients with high-risk FL as identified by POD24 and should be evaluated in prospective clinical trials.

IF 4.484 (2017); International audience; To evaluate the outcomes of salvage third autologous stem cell transplantation (ASCT) in patients with relapsed multiple myeloma. We analyzed 570 patients who had undergone a third ASCT between 1997 and 2010 (European Society for Blood and Marrow Transplantation data), of whom 482 patients underwent tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients underwent an upfront ASCT with second and third transplantations after subsequent relapses (ARARA group). With a median follow-up after salvage third ASCT of 61 months in the AARA group and 48 months in the ARARA group, the day +100 nonrelapse mortality in the 2 groups was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression-free survival was 13 and 8 months, and median overall survival (OS) was 33 and 15 months. In the AARA group, according to the relapse-free interval (RFI) from the second ASCT, the median OS after the third ASCT was 17 months if the RFI was

Summary We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86·2% vs. 84·3%). Further follow-up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow-up, 55·5 months); median progression-free survival (PFS) was 35·3 months and median overall survival (OS) was not reached. In patients with high-risk versus standard-risk cytogenetics, median PFS was 19·9 vs. 43·6 months (P

Response-adapted consolidation with bortezomib after ASCT improves progression-free survival in newly diagnosed multiple myeloma

Introduction The kidney is an important target organ in plasma cell dyscrasias, subjected to various mechanisms of injury such as tubular obstruction, hypercalcemia, and pre-existing disease. Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) is of concern as treatment-related toxicity (for instance infections and mucositis) is known to increase with renal impairment (RI). However, even severe MM-induced RI may recover with anti-myeloma treatment. We set out to compare three induction regimens in patients (pts) with transplant-eligible NDMM in terms of renal recovery and toxicity, MM response and associated adverse events (AEs). Pts from two prospective trials (NCT00833560, NCT01685814) were analyzed, provided post-induction (PInd) restaging data was available. They received three 3-week induction cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD); btz, lenalidomide (len), and dex (VRD); or three 4-week cycles with len, adriamycin, and dex (RAD). All pts had to have measurable disease, an estimated glomerular filtration rate (eGFR) of >30 ml/min and to be up to 60 (VCD) and 65 years (yrs) of age, respectively. VCD consisted of intravenous (IV) btz 1.3 mg/m² on day (D) 1, 4, 8, 11; IV cyclophosphamide 900 mg/m2D1; dex 20 mg D 1+2, 4+5, 8+9, 11+12. VRD of subcutaneous (SQ) btz 1.3 mg/m² D 1, 4, 8, 11; len 25 mg, D1-14; dex 20 mg D 1+2, 4+5, 8+9, 11+12; and RAD of len 25 mg D1-21; IV adriamycin 9 mg/m² D1-4; dex 40 mg D 1-4 + 17-20. MethodsThis is a secondary analysis of a phase 2 and a phase 3 study. We hypothesized MM disease response (and in turn, renal recovery) would be best with VRD. GFR was estimated by the MDRD IV or CKD-Epi formulas. The increase (and decrease, respectively) of renal function expressed by "GFRpost induction- GFRscreening" was tested for significance (p 50 ml/min and ≤ 70 ml/min (group II) were observed in 11.6 % of VCD pts, 29.9% of VRD and 25.2 % of RAD pts, respectively. 78.2% of VCD pts, 56.1% of VRD and 63.9% of RAD pts had a baseline eGFR of > 70 ml/min (group III; pPR (p=.0387). In the whole cohort, proportion of patients in eGFR group I had decreased from 10.0 to 3.0% (p +2 ml/min(/1.73m²)/month, respectively. 25.7% of VCD, 29.4% of VRD and 23.3% of RAD pts fell into the +2 ml/min was achieved by 55.2% of VCD vs 42.1% of VRD treated pts, respectively (Figure 1; p +2 ml/min(/1.73m²)/month. It is tempting to speculate that either the difference between SQ and IV btz, differential effects of len and cyclophosphamide on kidney function or non-MM related factors account for these unexpected and discordant renal and MM responses. Kidney-specific AEs, urine protein studies and comorbidities will be presented. Disclosures Mügge: Celgene: Research Funding; Celgene, Janssen: Honoraria. Schreder:Janssen, Celgene: Consultancy, Honoraria. Schaefer-Eckart:Pfizer, Janssen, Celgene: Honoraria. Metzler:Bristol-Myers Squibb, Celgene: Consultancy, Honoraria. Hertenstein:RS Media: Research Funding. Maschmeyer:Gilead, Janssen Cilag, Astra Zeneca; BMS, Merk-Serono: Honoraria. Salwender:Janssen Cilag: Consultancy, Honoraria, Other: Travel grants; Celgene: Honoraria, Other: Travel grants; AMGEN: Honoraria, Other: Travel grants; Sanofi: Honoraria, Other: Travel grants; Bristol-Myers Squibb: Honoraria, Other: Travel grants; Takeda: Honoraria, Other: Travel grants; Oncopeptides: Honoraria, Other: Travel Grants. von Lilienfeld-Toal:Celgene, Oncopeptides: Consultancy, Honoraria. Straka:Celgene, Janssen, AMGEN: Consultancy, Research Funding, Speakers Bureau. Knop:Janssen, AMGEN, Bristol-Myers Squibb, Celgene: Consultancy, Honoraria. OffLabel Disclosure: Lenalidomide, adriamycin, dexamethsone in newly diagnosed multiple myeloma

Background:Long-term clinical and molecular remissions in patients with MCL following HDT and ASCT have been evaluated in only a few studies. Results are especially limited for remission duration over 5 years. So the curability of this disease remains an open question. Patients and methods:Altogether 61 patients with MCL were treated in our institution with ASCT from 1998 to April 2019 (50 1st-line ASCT, ten 2nd-line ASCT, one 3rd-line ASCT). The data were collected retrospectively in 29 and prospectively in 32 patients who participated in two clinical trials: the 1st-line therapy trials of the German Low Grade Lymphoma Study Group (GLSG, principal investigator W. Hiddemann [Dreyling M, Blood 2005] and the European Mantle Cell Lymphoma Network [Hermine O, Lancet 2016], respectively. The diagnosis was regularly approved by the reference pathology of the GLSG (W.K.). The induction therapy before 1st-line ASCT consisted of 6 courses CHOP (n=11), mostly combined with rituximab and followed by Dexa-BEAM, and 6 alternating courses of R-CHOP and R-DHAP (n=39), respectively. For the salvage treatment patients usually received three to four courses of the DHAP protocol or the ESHAP protocol, since 2001 also combined with rituximab.Stem cell apheresis was carried out in the Blood Transfusion Service following these protocols in remission. High-dose protocols: 1) total body irradiation with cyclophosphamide or melphalan and cytarabin (n=32) or 2) BEAM (n=29). Patients with partial remission after ASCT received a radiotherapy (RT) with 30-36 Gy in the field of persisting lymphoma, if possible (n=4). Since 09/2016 patients received a maintenance therapy with rituximab after ASCT (every 2 months, planned for 3 years, n=14). Further details are described in an earlier publication of our first 36 patients (Metzner B, Ann Hematol 2013). Response assessment was performed by careful clinical examination and by ultrasound, chest x-ray and partly CT at regular 3 - 12 monthly time points. In the case of long-term remission (≥ 5 years; n = 18), peripheral blood was regularly tested twice a year for minimal residual disease (MRD) by quantitative t(11;14) or allel specific IGH RQ-PCR and/or IGH-consensus PCR.Calculations were done using IBM SPSS Statistics Version 25. Data were analysed as of 01 July 2019. Results:With a median follow-up of 5 years (range 0.1-20) 10-year overall survival, progression-free survival (PFS) and freedom from progression (FFP) after 1st-line ASCT were 54%, 46% and 52%, respectively, after 2nd-line ASCT 42%, 20%and 20%, with a significant difference for PFS (p=0.045) and FFP (p=0.014) between 1st-line and 2nd-line cohort.Further prognostic factors (like sex, age, MIPI, bone marrow involvement, remission grade at ASCT: CR vs. PR, type of HDT: TBI vs. BEAM…) seemed to be without relevance (considering the small subgroups). Only one clinical relapse occurred after 5 years following ASCT in 1stor 2ndremission, respectively (one patient 6 years after 1st-line ASCT and another patient 7 years after 2nd-line ASCT and subsequent radiotherapy). So far, 18 patients experienced long-term remissions of at least 5 years (median 9 years, from 5 to 16 years). Fifteen of 17 tested patients were MRD negative at last follow-up, the two MRD positive patients (positive at a low level below the quantitative measuring range) had no clinical signs of relapse at last follow-up. None of these 18 patients had received rituximab maintenance therapy. None showed clinical criteria of "smoldering mantle cell lymphoma" at induction therapy. Treatment-related mortality at 100 days after ASCT was 1.6% (pneumonitis following TBI). One patient developed a secondary invasive malignancy in remission after ASCT (acute myeloid leukemia 4 years following TBI). Conclusion: Sustained long-term clinical and molecular remissions up to 16 years can be achieved following ASCT (without rituximab maintenance therapy), indicating the potential curative impact of 1st-line ASCT in MCL. The 2nd-line ASCT was obviously less effective. Disclosures Dreyling: Celgene: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: scientific advisory board, Research Funding, Speakers Bureau; Bayer: Consultancy, Other: scientific advisory board, Speakers Bureau; Gilead: Consultancy, Other: scientific advisory board, Speakers Bureau; Acerta: Other: scientific advisory board; Novartis: Other: scientific advisory board; Sandoz: Other: scientific advisory board. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding.

Introduction: The R-MegaCHOEP trial showed that dose-escalation of conventional chemotherapy necessitating autologous stem cell transplantation (ASCT) does not confer a survival benefit for younger patients (pts) with high-risk aggressive B-cell lymphoma in the Rituximab era (Schmitz et al., Lancet Oncology 2012; 13, 1250-1259). To describe efficacy and toxicity over time and document the long-term risks of relapse and secondary malignancy we present the 10-year follow-up of this study. Methods: In the randomized, prospective phase 3 trial R-MegaCHOEP younger pts aged 18-60 years with newly diagnosed, high-risk (aaIPI 2-3) aggressive B-cell lymphoma were assigned to 8 cycles of CHOEP (cyclophosphamide, doxorubcine, vincristine, etoposide, prednisone) or 4 cycles of dose-escalated high-dose therapy (HDT) necessitating repetitive ASCT both combined with Rituximab. Both arms were stratified according to aaIPI, bulky disease, and center. Primary endpoint was event-free survival (EFS). All analyses were calculated for the intention-to-treat population. This follow-up report includes molecular data based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) for MYC (IHC: 31/92 positive [40-100%], FISH: 14/103 positive), BCL2 (IHC: 65/89 positive [50-100%], FISH: 23/111 positive) and BCL6 (IHC: 52/86 positive [30-100%], FISH: 34/110 positive) and data on cell of origin (COO) classification according to the Lymph2CX assay (GCB: 53/88; ABC: 24/88; unclassified: 11/88). Results: 130 pts had been assigned to R-CHOEP and 132 to R-MegaCHOEP. DLBCL was the most common lymphoma subtype (~80%). 73% of pts scored an aaIPI of 2 and 27% an aaIPI of 3. 60% of pts had an initial lymphoma bulk and in 40% more than 1 extranodal site was involved. After a median observation time of 111 months, EFS at 10 years was 57% (95% CI 47-67%) in the R-CHOEP vs. 51% in the R-MegaCHOEP arm (42-61%) (hazard ratio 1.3, 95% CI 0.9-1.8, p=0.228), overall survival (OS) after 10 years was 72% (63-81%) vs. 66% (57-76%) respectively (p=0.249). With regard to molecular characterization, we were unable to detect a significant benefit for HDT/ASCT in any subgroup analyzed. In total, 16% of pts (30 pts) relapsed after having achieved a complete remission (CR). 23% of all relapses (7 pts) showed an indolent histology (follicular lymphoma grade 1-3a) and 6 of these pts survived long-term. In contrast, of 23 pts (77%) relapsing with aggressive DLBCL or unknown histology 18 pts died due to lymphoma or related therapy. The majority of relapses occurred during the first 3 years after randomization (median time: 22 months) while after 5 years we detected relapses only in 5 pts (3% of all 190 pts prior CR). 11% of pts were initially progressive (28 pts) among whom 71% (20 pts) died rapidly due to lymphoma. Interestingly, the remaining 29% (8 pts) showed a long-term survival after salvage therapy (+/- ASCT); only 1 pt received allogeneic transplantation. The frequency of secondary malignancies was very similar in both treatment arms (9% vs. 8%) despite the very high dose of etoposide (total 4g/m2)in the R-MegaCHOEP arm. We observed 2 cases of AML and 1 case of MDS per arm. In total 70 pts (28%) have died: 30 pts due to lymphoma (12%), 22 pts therapy-related (11 pts due to salvage therapy) (9%), 8 pts of secondary neoplasia (3%), 5 pts due to concomitant disease (2%) and 5 pts for unknown reasons. Conclusions: This 10-year long-term follow-up of the R-MegaCHOEP trial confirms the very encouraging outcome of young high-risk pts following conventional chemotherapy with R-CHOEP. High-dose therapy did not improve outcome in any subgroup analysis including molecular high-risk groups. Relapse rate was generally low. Pts with aggressive relapse showed a very poor long-term outcome while pts with indolent histology at relapse survived long-term. Secondary malignancies occurred; however, they were rare with no excess leukemias/MDS following treatment with very high doses of etoposide and other cytotoxic agents. Supported by Deutsche Krebshilfe. Figure Disclosures Nickelsen: Roche Pharma AG: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant; Janssen: Membership on an entity's Board of Directors or advisory committees. Hänel:Amgen: Honoraria; Celgene: Other: advisory board; Novartis: Honoraria; Takeda: Other: advisory board; Roche: Honoraria. Truemper:Nordic Nanovector: Consultancy; Roche: Research Funding; Mundipharma: Research Funding; Janssen Oncology: Consultancy; Takeda: Consultancy, Research Funding; Seattle Genetics, Inc.: Research Funding. Held:Roche: Consultancy, Other: Travel support, Research Funding; Amgen: Research Funding; Acrotech: Research Funding; MSD: Consultancy; Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding. Dreyling:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: scientific advisory board, Research Funding, Speakers Bureau; Bayer: Consultancy, Other: scientific advisory board, Speakers Bureau; Celgene: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Research Funding; Gilead: Consultancy, Other: scientific advisory board, Speakers Bureau; Novartis: Other: scientific advisory board; Sandoz: Other: scientific advisory board; Janssen: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Acerta: Other: scientific advisory board. Viardot:Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rosenwald:MorphoSys: Consultancy. Lenz:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding; Agios: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Employment, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy. Schmitz:Novartis: Honoraria; Gilead: Honoraria; Celgene: Equity Ownership; Riemser: Consultancy, Honoraria.

Since the outcome of relapsed/refractory aggressive non-Hodgkin’s lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P

Long-term clinical and molecular remissions in patients with mantle cell lymphoma (MCL) following high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) have been evaluated in only a few studies. Thirty-six patients with MCL received ASCT in our institution (27 patients undergoing first-line therapy, 8 patients undergoing second-line therapy, and 1 patient undergoing third-line therapy). In the case of long-term remission (≥5 years; n = 8), peripheral blood was tested for minimal residual disease (MRD) by t(11; 14) polymerase chain reaction (PCR) and immunoglobulin heavy-chain (IGH) PCR at the last follow-up. Ten-year overall survival (OS), progression-free survival (PFS), and freedom from progression (FFP) after first-line ASCT were 42 %, 43 %, and 54 %; after second-line ASCT, these were all 0 %. Four-year OS, PFS, and FFP for the first-line cohort were 75 %, 48 %, and 61 %, respectively. Four-year OS, PFS, and FFP after second-line ASCT were 55 %, 30 %, and 30 %, respectively. Treatment-related mortality (3 months after ASCT) was 0 %. The only prognostic factor for OS, PFS, and FFP was treatment line (p = 0.011, p = 0.046, and p = 0.023, respectively). No relapses occurred after 5 years following ASCT. So far, eight patients developed sustained long-term clinical and molecular complete remissions of up to 14.6 years following ASCT in the first treatment line. Sustained long-term clinical and molecular remissions can be achieved following ASCT in the first treatment line and apparently less frequent in the second treatment line.

Pharmacokinetics of 8 doses of rituximab (375 mg/m2) given in combination with 2-week cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone/prednisolone (CHOP-14) was determined by ELISA in 20 elderly patients with diffuse large B-cell lymphoma (DLBCL) 10 minutes before and after each infusion and 1 week and 1, 2, 3, 6, and 9 months after the last infusion. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling software (NONMEM VI). Concentration-time data were fitted into an open 2-compartment model and total clearance, central compartment volume, intercompartment clearance, and volume of distribution at steady-state (Vdss) were investigated. Total clearance was 9.43 mL/h and Vdss was 9.61 l. Rituximab clearance was reduced (8.21 mL/h vs 12.68 mL/h; P = .003) and elimination half-life was prolonged in women compared with men (t1/2β = 30.7 vs 24.7 days; P = .003). Body weight also affected Vdss (0.1 l increase of Vdss per kilogram above median of 75 kg). A sex-dependent effect and the higher weight of males contribute to their faster rituximab clearance, which might explain why elderly males benefit less from the addition of rituximab to CHOP than females. This trial was registered on www.clinicaltrials.gov as numbers NCT00052936, EU-20243 (RICOVER-60 Trial), EU-20534, and NCT00726700 (Pegfilgrastim Trial).

Purpose Patients with Richter's syndrome (RS) have a poor prognosis with conventional chemotherapy. The aim of this study was to evaluate the outcome after autologous stem-cell transplantation (autoSCT) or allogeneic stem-cell transplantation (alloSCT) in RS. Patients and Methods A survey was sent to all European Group for Blood and Marrow Transplantation centers assessing transplantations performed for RS. Eligibility criteria included a diagnosis of RS or secondary lymphoma before SCT, age ≥ 18 years, and SCT performed from 1997 to 2007. Data were analyzed by descriptive statistics and methods from survival analysis. Results Fifty-nine patients were registered. Thirty-four patients had received autoSCT, mostly because of chemotherapy-sensitive disease, and 25 had received alloSCT, with 36% being refractory to chemotherapy at SCT. In 18 allograft recipients (72%), reduced-intensity conditioning (RIC) was used. Three-year estimates of the probabilities of overall survival and relapse-free survival (RFS) and the cumulative incidences of relapse and nonrelapse mortality were 36%, 27%, 47%, and 26% for alloSCT and 59%, 45%, 43%, and 12% for autoSCT, respectively. Taking into account the limitations set by the low number of events and age younger than 60 years, chemotherapy-sensitive disease and RIC were found to be associated with superior RFS after alloSCT in multivariate analysis. Factors with a significant impact on autoSCT could not be identified. Conclusion Patients with RS who are sensitive to induction chemotherapy appear to benefit from consolidation with transplantation strategies, and prolonged survival was observed in a proportion of patients.

The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 μg) after high-dose chemotherapy. Highly variable leukocyte peaks were measured and grouped as low (quartile 1; leukocytes 100-10 100/μL), medium (quartile 2; leukocytes > 10 100-18 300/μL), and high (quartiles 3/4; leukocytes > 18 300-44 800/μL). G-CSF responsiveness (low vs medium vs high) was inversely correlated with febrile neutropenia (77% vs 60% vs 48%; P = .0037); the rate of infection, including fever of unknown origin (91% vs 67% vs 54%; P < .0001); days with intravenous antibiotics (9 vs 6 vs 5; P < .0001); and antifungal therapy (P = .042). In multivariate analysis, G-CSF responsiveness remained the only factor significantly associated with infection (P = .016). In addition, G-CSF responsiveness was inversely correlated with grade 3/4 oral mucositis (67% vs 33% vs 23%; P < .0001). G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy. This study is registered at http://www.clinicaltrials.gov as NCT01085058.

Metabolic syndrome (MetS) is defined as a clustering of five factors including (1) fasting hyperglycaemia (2) hypertriglyceridaemia (3) low HDL cholesterol (4) hypertension (5) obesity (high waist circumference). According to the International Diabetes Federation harmonised definition, a large waist circumference plus any other two features meet criteria for diagnosis of MetS. It is associated with raised risk of cardiovascular disease (CVD) by 3-fold and is increasingly recognised in patients after HCT. Recent guidelines for long-term HCT survivors recommend screening for MetS. We performed a large cross-sectional service evaluation of HCT survivors in centres working in accordance with international screening guidelines. We have previously presented interim results regarding the prevalence of MetS and associated risk factors and now present the final results. This was an EBMT approved cross-sectional, non-interventional study of consecutive HCT patients (allo and auto) aged 18+ years and a minimum of 2 year post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. Centres completed proformas incorporating routine recording of the MetS parameters (given above) as well as performance status (ECOG); evidence of cardiovascular events; family history of premature CVD; and relevant drug history. Univariate comparison of patients and HCT characteristics between the 2 groups (MetS vs no MetS) was performed using non-parametric Mann-Witney U test for continuous variables and Chi-square test or Fisher test for categorical variables. All tests were two-sided. Multivariate logistic regression analyses were performed to predict MetS and cardiovascular events. Variables with a p-value Table 1 gives the population demographic, age, primary disease and transplant details. The prevalence of MetS was 30.4% (allo 29%, auto 35.6% ns). There was a significant difference in prevalence by age at follow-up (p This large study in HCT survivors confirms high prevalence of metabolic syndrome following both allogeneic and autologous HCT of 30.4% overall rising to 39% in those aged over 50 years at follow-up. The data support MetS being an age-related late effect of HCT that is strongly associated with not only cardiovascular events but also the occurrence of second cancers. Further analysis examining the relationship between intensity of treatment and prevalence of MetS and CVE is needed. The data supports routine screening for MetS of both allo and auto HCT patients. Early intervention of reversible features of MetS with lifestyle and medical management may reduce the risk of cardiovascular events, but this needs be tested in a randomised controlled trial setting. Meanwhile, screening and management should be robustly integrated within routine HCT long-term follow-up care. Table 1. Table 1. Disclosures Cortelezzi: janssen: Consultancy; novartis: Consultancy; roche: Consultancy; abbvie: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Bristol Myers: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Molmed: Consultancy; Janssen: Honoraria, Research Funding, Speakers Bureau. Kroeger:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; JAZZ: Honoraria; Sanofi: Honoraria; Neovii: Honoraria, Research Funding. Snowden:Jazz & Sanofi: Other: Speaker fees at ASH; Jannssen/J&J: Other: Speaker fees.

Introduction High-dose chemotherapy and stem cell transplant (SCT) remains a standard of care in medically fit patients (pts) with newly diagnosed (ND) MM. Induction triplets with at least one of the newer compounds are recommended. Bortezomib (V), lenalidomide (R) and dexamethasone (D; VRD) ranks among the most effective regimens and VRD/SCT was superior to VRD alone in an RCT. In a phase 2 study, we demonstrated RAD induction (lenalidomide 25 mg d1-21; Adriamycin 9 mg/m2 iv d1-4; dexamethasone 40 mg d 1-4 and 17-20 every 4 weeks) followed by SCT to be safe and effective (Knop et al., Leukemia 2017). Therefore, we decided to compare RAD versus (vs) VRD (lenalidomide 25 mg, d1-14; subcutaneous bortezomib 1.3 mg/m2 d 1, 4, 8, 11; dexamethasone 20 mg d 1+2, 4+5, 8+9, 11+12 every 3 weeks) induction (3 cycles each) in an RCT. MethodsThe current study was set up according to a double 2x2-factorial design to enrol transplant-eligible pts up to 65 years. The post-induction (PI) complete response (CR) rate as per IMWG criteria was the efficacy co-primary endpoint. We hypothesized the CR rate following RAD to be non-inferior to VRD which was estimated to be 20%. The study was powered to confirm non-inferiority of RAD at a margin of 10% with a one-sided alpha level of .05. Cytogenetic characterization was performed by fluorescence in situ hybridization (FISH) from CD138-enriched plasma cells. Minimal residual disease (MRD) was assessed by second-generation eight-color flow cytometry (FC; EuroFlow protocol). Bone marrow (BM) samples from baseline and defined restaging time points were analyzed for an acquisition of ⩾107cells/sample. In a subgroup of 103 pts, we evaluated the applicability of comprehensive immunoglobulin (Ig) amplicon next generation sequencing (NGS) to detect molecular MRD markers and to compare the results with FC. NGS-based marker screening was performed in baseline BM. Sequencing libraries were prepared using 2-step PCR employing multiplex primer sets for IGH V-D-J (FR1, FR2 and FR3), IGH D-J and IGK loci (V-J and KDe). For MRD detection, we used 1-step library preparation with the same primer sets. Results476 pts with a median age of 55 (range, 32-65) years were randomized between 05/2012 and 06/2016 and 469 received at least one dose of study drug. High-risk (HR) FISH abnormalities comprised del17p (11.3% of pts); t(4;14) (11.7%); and t(14;16) (4.5%). 232 pts were randomized to receive RAD, and 237 to VRD, respectively. 90.5% of RAD vs 93.7% of VRD pts completed all 3 cycles. PI CR rate was 13.5% (95% CI, 9.4%-18.7%) with RAD vs 13.4% (95% CI, 9.3-18.5) with VRD, (P=.971). Rates of ≥VGPR were 40.6% (50% CI, 34.2%-47.3%) with RAD vs 48.9% (95% CI, 42.3-55.6%) with VRD (P=.076). In pts with HR cytogenetics, rates of ≥VGPR were 43.3% (RAD) vs. 59.3% (VRD; P=.096). From 317 pts with paired samples, 33/151 (21.9%) of RAD vs 45/166 (27.1%) of VRD pts were FC MRD negative (P=.169) following induction at a median sensitivity level of 6.73x10-6. 197/239 positive pts (82.4%%) had MRD levels above 0.01%, and 42 (17.6%), between 0.0001 and 0.01%. Flow MRD negativity as per IMWG MRD criteria (Kumar et al, Lancet Oncol 2016) was seen in 8/151 (5.2%) pts with RAD vs 6/166 (3.6%) with VRD (P=.27). The remainder of pts did not (yet) fulfil IMWG CR for various reasons. NGS marker screening identified at least 1 Ig marker in 98/103 evaluable patients. To date, 47/98 pts were analyzed for NGS MRD following induction. Four out of 47 (8.5%) subjects were sequencing negative (3/4 post-VRD) with all of them also being IMWG FC MRD negative. One VRD patient died during induction for a mortality rate of 0.2 %. 62.1% of RAD vs 55.3% of VRD pts experienced at least one serious adverse event (SAE; p=.16). SAEs with relationship to study drugs of at least °3 severity occurred in 26.3% (RAD) vs 23.6% (VRD) pts (p=.523). ConclusionsTo the best of our knowledge, this is the first RCT to compare two R-based triplets in SCT-eligible pts. The co-primary efficacy endpoint was met with identical PI CR rates of around 13% for RAD and VRD, respectively. However, a trend emerges to favor VRD over RAD in terms of at least VGPR including HR FISH subjects. Analysis of MRD by multicolor FC showed 5% of pts to be already IMWG flow MRD-negative. Results for all 98 pts evaluable for NGS MRD will be presented. As of yet, too few progression events have occurred to estimate the second co-primary endpoint, 3-year progression-free survival. Longitudinal response and MRD analysis are ongoing. Disclosures Langer: Celgene: Consultancy. Mügge:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Amgen: Honoraria. Blau:Amgen: Other: Advisory board; BMS: Other: Advisory board; Novartis: Other: Advisory boards; Takeda: Other: Advisory board; Janssen: Other: Advisory board, Research Funding; Celgene: Other: Advisory board, Research Funding. Rollig:Janssen: Research Funding; Bayer: Research Funding. Dechow:AMGEN: Consultancy; Celgene: Honoraria. Gramatzki:Affimed: Research Funding. Brümmendorf:Merck: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Schmidt:Gilead: Honoraria, Other: Travel Grants; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Celgene: Honoraria. Knop:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

Background: 6 cycles CHOP-like chemotherapy plus rituximab (6x R-CHOP) are the standard treatment for young patients with DLBCL. The MInT trial established a subgroup with favourable prognosis as defined as aaIPI=0 and no bulky disease [Pfreundschuh et al., Lancet Oncol 2006; 7: 379-391] with a 3-year EFS of 89%, PFS of 95% and OS of 98%. We hypothesized that 4 cycles of CHOP plus 6 applications of rituximab are non-inferior to the standard treatment of 6x R-CHOP in this population. Patients and Methods: 18 to 60 year-old patients, aaIPI =0 without bulky (≥7.5 cm) disease were randomized to receive 6x R-CHOP or 4x R-CHOP+2xR at 21-day cycles. Radiotherapy was not planned to be given except for prophylactic radiotherapy of the contralateral testis in patients with testicular lymphoma. The primary endpoint was progression free survival (PFS) with events defined as progressive disease, relapse or death. Assuming a 93% 3-years PFS for the 6x R-CHOP arm, it was planned to tolerate an impairment of 5.5% by reducing the number of courses to 4x R-CHOP+2xR to prove non-inferiority with a power of 80% and an alpha-error of 5% (one-sided). Results: Between 12/2005 and 10/2016, 592 patients were randomized in the international multi-center FLYER trial and 588 patients were evaluable for this final analysis. 295 patients were assigned to receive 6x R-CHOP and 293 were assigned to receive 4x R-CHOP+2xR. There were no relevant differences in demographics (median age: 48 years, 99% aaIPI=0, 1% aaIPI=1, 0.3% bulky disease), protocol adherence and toxicity between the two arms. PFS, EFS and OS after 4x R-CHOP+2xR were as good as after 6x R-CHOP. After 66 months median observation, the 3-year PFS rate of the patients receiving 4x R-CHOP+2xR was 96% vs. 94% of patients receiving 6x R-CHOP (p=0.760). The lower limit of the 95% CI of the difference between treatment arms was 0% and excludes -5.5% demonstrating the non-inferiority. The 3-year EFS was identical (89%) in both treatment arms. The 3-years OS was 99% in patients receiving 4x R-CHOP+2xR and 98% in patients receiving 6x R-CHOP. In a multivariable analysis adjusting for strata (stage and E-involvement), the hazard ratio of 4x R-CHOP+2xR compared to 6x R-CHOP was 1.0 (95% CI: 0.7-1.6; p=0.896) for EFS, 0.9 (95% CI: 0.5-1.6; p=0.797) for PFS, and 0.8 (95% CI: 0.4-1.9; p=0.671) for OS. With respect to relapse rate there was also no significant difference between the two treatment arms. 4% (95% CI 2-7%) of the patients in the 4x R-CHOP+2xR arm relapsed vs. 5% (95% CI 3-8%) of the patients in the 6x R-CHOP arm. 33% of relapses occurred in the first two years after study inclusion but continue to be seen with longer follow-up in both arms. Conclusion: In young patients with favourable prognosis DLBCL outcome after 4x R-CHOP+ 2xR is non-inferior compared to the previous standard 6x R-CHOP. Thus, chemotherapy can be spared without compromising prognosis in this population. Supported by Deutsche Krebshilfe Figure. Figure. Disclosures Poeschel: Roche: Other: Travel grants; Amgen: Other: Travel grants. Held:BMS: Consultancy, Other: Travel grants, Research Funding; Amgen: Research Funding; Roche: Consultancy, Other: Travel grants, Research Funding; MSD: Consultancy; Spectrum: Research Funding. Holte:Roche, Norway: Research Funding; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Viardot:Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Borchmann:Novartis: Consultancy, Honoraria. Keller:Celgene: Research Funding; BMS: Consultancy; Takeda: Consultancy, Research Funding; Janssen-Cilag: Consultancy, Equity Ownership; Roche: Consultancy; MSD: Consultancy. Schmidt:Gilead: Honoraria, Other: Travel Grants; Celgene: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants. Marks:Merck: Honoraria; BMS: Honoraria; Servier: Honoraria. Stilgenbauer:Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmcyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffmann La-Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schmitz:Riemser: Honoraria, Other: Travel grants; Kite/Gilead: Honoraria, Other: Travel grants; Novartis: Honoraria, Other: Travel grants; Celgene: Other: Travel grants; Roche: Honoraria. Murawski:Takeda: Consultancy; Janssen: Other: Travel grants.

7574Background: The role of RT to B and E for young patients with good-prognosis DLBCL is ill-defined. Methods: 18-60 year-old patients (aaIPI = 0 with B [≥7.5 cm], aaIPI 1) qualifying for radiothe...

Lymphoplasmacytic lymphoma (LPL) is an indolent lymphoma with moderate sensitivity to conventional chemotherapy. This study investigated whether the addition of rituximab to standard chemotherapy improves treatment outcome in LPL and the subgroup of LPL patients fulfilling the criteria of Waldenstroem's macroglobulinemia (WM). A total of 69 patients with previously untreated LPL were enrolled into the trial; 64 patients were evaluable for treatment outcome. In all, 48 of the 64 LPL patients fulfilled the criteria of WM. Patients were randomly assigned to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, n=34) or CHOP (n=30). R-CHOP resulted in significantly higher overall response (OR) rate (94 vs 67%, P=0.0085) in the LPL patients and in the WM subgroup (91 vs 60%, P=0.0188). With a median observation time of 42 months, R-CHOP induced a significantly longer time to treatment failure (TTF) with a median of 63 months for R-CHOP vs 22 months in the CHOP arm in the LPL patients (P=0.0033) and in the WM subgroup (P=0.0241). There was no major difference of treatment-associated toxicity between both treatment groups. These data indicate that the addition of rituximab to front-line chemotherapy improves treatment outcome in patients with LPL or WM.

To determine the maximum tolerated dose of a bi- and tri-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone plus etoposide (CHOEP) regimen without stem-cell support.Randomized phase I/II multicenter four-level (cyclophosphamide: 1000-1200-1400-1600 mg/m2; doxorubicin: 55-60-65-70 mg/m2; etoposide: 375-450-525-600 mg/m2) dose escalation study with CHOEP-14 and CHOEP-21 in young patients (18-60 years) with newly diagnosed aggressive non-Hodgkin's lymphoma. Dose-limiting toxicity was defined as thrombocytopenia80,000/mm3 and leukocytopenia2500/mm3 on days 16 (CHOEP-14) and 23 (CHOEP-21) or prolonged (4 days) leukocytopenia (1000/mm3) or thrombocytopenia (20,000/mm3).One hundred and thirty-nine patients (high-CHOEP-14: 47, high-CHOEP-21: 92) were randomly allocated to the study. Maximal tolerated dose was level 2 for CHOEP-14 and level 4 for CHOEP-21. With a less favorable profile of patients in CHOEP-14, 4-year event-free survival was 47.9% after high-CHOEP-14 and 66.2% after high-CHOEP-21, 4-year overall survival 62.1% after high-CHOEP-14 and 73.4% after high-CHOEP-21, respectively.Significant dose escalations of CHOEP are possible with granulocyte colony-stimulating factor support, with different chemotherapy models favoring the maximally escalated bi- or tri-weekly regimen, respectively. Because a higher total dose can be achieved with six cycles of the tri-weekly compared with the biweekly regimen, CHOEP-21 at dose escalation level 3 was chosen for a nationwide randomized comparison with baseline CHOEP-21 in a subsequent phase III trial.