Minimum tolerable interval of 90yttrium ibritumomab-tiuxetan to autologous stem cell transplantation after high-dose chemotherapy with carmustin, etoposide, cytarabine, and melphalan for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.

6543 Background: High-dose therapy and autologous stem cell transplantation (ASCT) in patients (pts) with aggressive B-NHL failing from immunochemotherapy including rituximab show poor outcome with 3y PFS of 39% (Gisselbrecht et al. JCO 2010). Combining BEAM with 90yttrium ibritumomab tiuxetan is a promising option to enhance the efficacy of the high-dose regimen. Methods: Pts without disease progression during salvage therapy of relapsed or refractory CD20+ aggressive B-NHL were included in this prospective, multicenter, phase I/II trial. Primary endpoint was the maximum tolerated dose of 90Yttrium ibritumomab tiuxetan given as close as possible to ASCT defined as <2 pts with dose limi…

FIRST-LINE THERAPY OF T-CELL LYMPHOMA: ALLOGENEIC OR AUTOLOGOUS TRANSPLANTATION FOR CONSOLIDATION - FINAL RESULTS OF THE AATT STUDY

Survival of elderly patients with multiple myeloma-Effect of upfront autologous stem cell transplantation

Abstract Background The aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60–79 years) with myeloma. Methods We analysed relative survival (RS) of patients diagnosed in 1998–2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population-based German Cancer Registries). Results Utilisation of ASCT has increased rapidly between 2000–2002 and 2009–2011 (60–64years: 7.0–43.0%; 65–69 years: 6.6–23.7%; 70–79 years: 0.4–4.0%). Comparison of 5-year RS of patients f…

Late Non-Relapse Mortality (NRM) after Standard-of-Care (SOC) CAR-T Cell Therapy for Large B-Cell Lymphoma (LBCL): Frequency, Causes, and Risk Factors.a GLA/DRST Real World Analysis

Abstract Introduction Although the labeled CD19 targeting CAR-T cell constructs axi-cel and tisa-cel are generally associated with an acceptable safety profile, non-relapse deaths can occur. Little is known about timing, causes and predictors of NRM following SOC CAR-T cell therapy for LBCL. Here, we analyzed frequency, causes, and risk factors of non-relapse deaths with focus on late NRM (beyond 4 weeks after dosing) using registry data provided by the DRST, the national partner of the EBMT. Methods Patients were selected from 356 consecutive patients who received SOC CAR-T treatment of LBCL between November 2018 and April 2021 at 21 German centers and were registered with the DRST/EBMT. B…

Improved relapse-free survival after autologous stem cell transplantation does not translate into better quality of life in chronic lymphocytic leukemia: Lessons from the randomized European Society for Blood and Marrow Transplantation-Intergroup study

Item does not contain fulltext In chronic lymphocytic leukemia (CLL) medical progress is driven by clinical studies with relapse-free survival (RFS) as the primary endpoint. The randomized EBMT-Intergroup trial compared high-dose therapy and autologous stem cell transplantation (ASCT) to observation and demonstrated a substantial improvement of RFS without showing improved overall survival for the transplant arm. Here we report quality of life (QoL) information of the first 3 years following randomization from that study. The main objective was to assess the impact of treatment on QoL over time. Two secondary analyses were performed to further investigate the impact of ASCT and relapse on Q…

Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas

The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and brid…

Alemtuzumab Combined with Dexamethasone, Followed By Alemtuzumab Maintenance or Allo-SCT in "ultra High-risk" CLL: Final Results from the CLL2O Phase II Study

CLL with deletion 17p (17p-) or refractory to fludarabine (F)-based regimens is characterized by poor prognosis. The cooperative French/German CLL2O study aimed at achieving deep and durable response in this population by combining alemtuzumab (A) and dexamethasone (D) induction, followed by consolidation with A maintenance or allogeneic stem-cell transplantation (allo-SCT). Induction treatment consisted of subcutaneous A (30mg, 3x weekly) combined with oral D (40 mg days 1-4 and 15-18), both at 28 day cycles, and prophylactic pegfilgrastim 6 mg on days 1 and 15. If at least SD was achieved after 3 cycles, consolidation was scheduled with either allo-SCT or A maintenance (30mg every 2 weeks…

Residual Abdominal Lymphadenopathy after Intensive Frontline Chemoimmunotherapy Is Associated with Inferior Outcome Regardless of MRD Status in Advanced Chronic Lymphocytic Leukemia (CLL)

Abstract Introduction: In CLL, chemoimmunotherapies (CIT) and combinations with novel agents have proven to be highly effective with regard to eradication of minimal residual disease (MRD), while complete remissions (CR) are frequently not achieved due to residual lymphadenopathy. We have previously reported that minimal residual disease (MRD) negativity after CIT is a prognostic factor irrespective of the clinical response (Kovacs et al., JCO 2016). Because inferior outcome was observed in small subgroups of patients (pts) with residual lymphadenopathy, we analyzed the prognostic value of residual lymphadenopathy after CIT in comparison to MRD detection in a larger pt population. Methods: …

Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial

Background: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. Methods: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18–70 years, had acute myeloid leukaemia in first or consecutive complete haematological remissi…

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)

Abstract Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Out…

High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) Has a Significant but Transient Impact on Quality of Life: Lessons From the Chronic Lymphocytic Leukemia (CLL) ASCT Study by the CLL Subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Abstract Abstract 1989 Objective: High-dose therapy (HDT) and ASCT is the standard of care in a variety of hematologic malignancies. Whereas for some indications a survival advantage for HDT and ASCT has been demonstrated, a benefit only in terms of better progression-free survival has been shown for CLL. Because of this the quality of life (QoL) deserves particular attention. QoL assessment was a major focus of a randomized controlled EBMT-Intergroup trial on the value of HDT compared to observation in first or second remission of CLL (Michallet, Blood, 2011). Methods: 222 patients were enrolled into the study and allocated to either ASCT or observation. In the transplant arm, 72% received…

Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia – a study of the Acute Leukemia Working Party of the EBMT

The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients ≥55 years LFS was best with FLAMSA-Chemo without significant differences…

High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses.

Preliminary evidence suggests that the multikinase inhibitor sorafenib has clinical activity in FLT3-ITD-positive (FLT3-ITD) acute myeloid leukemia (AML). However, the quality and sustainability of achievable remissions and clinical variables that influence the outcome of sorafenib monotherapy are largely undefined. To address these questions, we evaluated sorafenib monotherapy in 65 FLT3-ITD AML patients treated at 23 centers. All but two patients had relapsed or were chemotherapy-refractory after a median of three prior chemotherapy cycles. Twenty-nine patients (45%) had undergone prior allogeneic stem cell transplantation (allo-SCT). The documented best responses were: hematological remi…

Polatuzumab Vedotin in Relapsed and Refractory (r/r) Large B-Cell Lymphoma (LBCL): Real-World Data of the German National Compassionate Use Program (CUP)

Introduction The antibody-drug conjugate polatuzumab vedotin (Pola) has recently been approved in combination with bendamustine and rituximab (Pola-BR) for patients with r/r diffuse LBCL (DLBCL). Methods To characterize the efficacy of Pola-BR in a real-world setting, we retrospectively analyzed data from 97 patients with r/r LBCL who were treated with Pola in 24 German centers within the national CUP. Clinical baseline and follow-up (FU) data were collected by chart review and summarized descriptively. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. Fisher's exact test was used to compare categorical factors between gro…

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION (AUTOHSCT) IN CLL: FIRST RESULTS OF AN EBMT RANDOMIZED TRIAL COMPARING AUTOTRANSPLANT VERSUS WAIT AND WATCH

Abstract Abstract 877 This phase-III randomized EBMT-intergroup trial studied the impact of a consolidating autoHSCT vs no consolidation for patients with CLL in Binet stage A progressive, B or C , in CR, nodular PR or VGPR after first or second line therapy. The primary objective was to show that autoHSCT increased the 5-year progression-free survival (PFS) by 30%. Although it had been calculated that 270 patients were to be randomized, the study was terminated by the steering committee in July 2007 due to poor accrual. Here we present a first analysis based on 69% of expected follow-up forms. Results: Between November 2001 and July 2007, 223 patients were enrolled (SFGM-TC/FCLLG n=98, MRC…

Alemtuzumab Plus Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allogeneic Transplantation in Ultra High-Risk CLL: Updated Results From a Phase II Study of the Gcllsg and fcgcll/MW

Abstract Abstract 716 CLL patients characterized by 17p-, TP53 mutation or refractoriness to fludarabine (F)-based therapy show a very poor prognosis (“ultra high-risk CLL”). Although alemtuzumab (A) showed efficacy in these cohorts, the rate and duration of remissions remain unsatisfactory. Aim of the CLL2O study was to achieve higher overall response rates (ORR) by adding high-dose dexamethasone (D) to A during induction and investigating the consolidation effect of prolonged A or allogeneic stem-cell transplantation (allo-SCT), respectively. Induction treatment consisted of subcutaneous A, 30 mg weekly × 3 for 28 days, combined with oral D, 40 mg on days 1–4 and 15–18, and prophylactic p…

Standard of Care CAR-T Cell Therapy for Large B-Cell Lymphoma (LBCL): Does Bridging Efficacy Matter? a German GLA/DRST Real World Analysis

Abstract Introduction The CD19 targeting CAR-T cell constructs axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have become an accepted standard salvage treatment of LBCL beyond the second line. Patients scheduled for approved CAR-T cell therapies usually have 4-8 weeks wait time for CAR-T cell infusion, thus often requiring bridging strategies in rapidly progressing patients to achieve disease control until start of lymphodepletion. It is still unclear, however, if the adverse impact of active progressive lymphoma can be overcome by successful bridging. We have addressed this question using registry data provided by the German Registry for Stem Cell Transplantation (DRST),…

Distinct Activities of Glycolytic Enzymes Identify Chronic Lymphocytic Leukemia Patients with a more Aggressive Course and Resistance to Chemo-Immunotherapy.

A higher capacity to grow under hypoxic conditions can lead to a more aggressive behavior of tumor cells. Determining tumor activity under hypoxia may identify chronic lymphocytic leukemia (CLL) with aggressive clinical course and predict response to chemo-immunotherapy (CIT). A metabolic score was generated by determining pyruvate kinase and lactate dehydrogenase, key enzymes of glycolysis, ex vivo in primary CLL samples under normoxic and hypoxic conditions. This score was further correlated with clinical endpoints and response to CIT in 96 CLL patients. 45 patients were classified as metabolic high risk (HR), 51 as low risk (LR). Treatment-free survival (TFS) was significantly shorter in…

Comparison of a New Reduced Toxicity Myeloablative Treosulfan and Fludarabine Preparative Regimen with Myeloablative Busulfan or Melphalan in Combination with Fludarabine in Older Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes: A Retrospective Matched Pair Analysis of Patients from a Prospective Randomized Trial and the European Blood and Marrow Transplantation Society Registry

Background The best preparative regimen for the growing number of older acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients undergoing allogeneic hematopoietic cell transplantation (HCT) from matched related (MRD) or unrelated donors (MUD) remains undefined. A large randomized phase III trial (MC-FludT.14/L study: ClinicalTrials.gov Identifier: NCT00822393) recently demonstrated that myeloablative intravenous (IV) treosulfan (10 g/m² IV on days -4 to -2) in combination with fludarabine (TreoFlu) improves outcome in older and/or comorbid patients with AML in complete remission (CR) or MDS compared with the reference reduced intensity busulfan (0.8 mg/kg IV in 6-hour inte…