The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians – Oral Session
2019; Springer Nature; Volume: 54; Issue: S1 Linguagem: Inglês
10.1038/s41409-019-0562-9
ISSN1476-5365
Tópico(s)Transplantation: Methods and Outcomes
ResumoLate-breaking abstractsO177 Comparable outcome after 10/10 and 9/10 HLA-matched unrelated donor stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCY) for GVHD prophylaxis, on behalf of the ALWP-EBMTFrancesca Lorentino1, Myriam Labopin2,3,4, Fabio Ciceri1, Luca Vago1, Katharina Fleischhauer5, Boris Afanasyev6, Nicolaus Kröger7, Jan J. Cornelissen8, Montserrat Lovira9, Ellen Meijer10, Antonin Vitek11, Ahmet Elmaagacli12, Didier Blaise13, Arnon Nagler2,14, Mohamad Mohty2,3,4 1 San Raffaele Scientific Institute, Milan, Italy, 2 Université Pierre and Marie Curie, Paris, France, 3 Unite´ de Recherche Mixte en Sante´ (UMR_S) 938, INSERM, Paris, France, 4 Hôpital Saint-Antoine, AP-HP, Paris, France, 5 Essen University Hospital, Institute for Experimental Cellular Therapy, Essen, Germany, 6 Raisa Gorbacheva Memorial Research Institute, The First Pavlov State Medical University of St-Petersburg, St Petersburg, Russian Federation, 7 University Hospital Eppendorf, Hamburg, Germany, 8 Erasmus MC Cancer Institute University Medical Center Rotterdam, Rotterdam, Netherlands, 9 Hospital Clinic, Institute of Hematology & Oncology, Barcelona, Barcelona, Spain, 10 University Medical Center, Amsterdam, Netherlands, 11 Institute of Hematology and Blood Transfusion, Prague, Prague, Czech Republic, 12 Asklepios Clinic St. Georg, Hamburg, Germany, 13 Institut Paoli Calmettes, Marseille, France, 14 Chaim Sheba Medical Center, Tel-Hashomer, Israel Background: PTCy is largely adopted as GvHD-prophylaxis backbone in haploidentical transplantation. The encouraging results prompted investigations to assess PTCy also in unrelated donor (UD) setting. High-resolution HLA-matching contributes to UD-HSCT success; however, due to the selective in-vivo deletion of alloreactive T-cells, PTCy could modulate HLA-matching impact on UD-HSCT. Methods: We compared the outcomes of acute leukemia patients receiving 10/10 (n=431) and 9/10 (n=234) HLA-allele matched UD-HSCT with PTCy GvHD-prophylaxis, reported to the ALWP-EBMT in 2010-2017. Primary endpoint was GvHD-free & Relapse-free survival (GRFS). Secondary endpoints were leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD, relapse and transplant-related mortality (TRM). Table 1 illustrates patients' characteristics. The power to detect a 2-years 10% difference GRFS between the 2 groups was 83% (alpha 2-sided=5%). Results: Outcome endpoints at 2 years were not different between 10/10 and 9/10 UD-HSCT (GRFS: 42±5% and 43±7%, p=0.5; LFS: 56±5% and 55±7%, p=0.7; OS: 63±5% and 60±8%, p=0.9, respectively). The 100-day CI of grade≥2 and grade≥3 aGvHD were comparable for 10/10 and 9/10 UD (31±5% and 28±6%, p=0.4 and 10±3% and 9±3%, p=0.5, respectively). Likewise, the 2-y CI of cGvHD and extensive cGvHD were similar between 10/10 and 9/10 UD (32±5% and 38±7%, p=0.2 and 17±4% and 15±5%, p=0.4, respectively). The 2-y CI of TRM was 19±4% after 10/10 and 17±5% after 9/10 UD-HSCT (p=0.4). Relapse incidence at 2-y was 25±5% for 10/10 and 28±6% for 9/10 UD-HSCT (p=0.6). After adjustment for diagnosis, patient age, disease status, Karnofsky PS, donor/patient gender and CMV, conditioning intensity, additional use of ATG, the multivariable model showed no effect of donor HLA-matching on outcomes. Compared to 10/10 UD, the hazards for GRFS was 0.9 for 9/10 UD (p=0.2), the HR for LFS was 0.9, p=0.3 and the HR for OS was 1, p=0.8. Moreover, compared to 10/10 UD, 9/10 UD-HSCT yelded similar hazards for grade≥2 aGvHD (HR: 0.8, p=0.2), cGvHD (HR: 1.2, p=0.3), TRM (HR: 0.7, p=0.2) and relapse (HR: 1, p=0.9). No interaction was found between donor type and additional ATG use. Variables associated with GRFS were active disease (HR 2.1 compared to 1st CR, p< 10-5) and Karnofsky PS≥90% (HR 0.6, p< 10-5). Conclusions: In the present series of acute leukemia patients transplanted with PTCy, we report comparable survival with 9/10 and 10/10 HLA-matched UD-HSCT, across all disease stages, suggesting that this platform could alleviate the detrimental effect of single HLA-allele mismatching. These results warrant prospective comparative trials of PTCy versus standard use of ATG-based GVHD prophylaxis in matched and mismatched UD-HSCT. 10/10-UD (n=431)9/10-UD (n=234) p Median follow-up, months18 (5-35)20 (11-31)0.5Patient median age43 (18-76)48 (19-73)0.1Diagnosis: AML; ALL313 (73%); 118 (27%)170 (73%); 64 (27%)0.9Disease status: CR1; CR>1; Advanced278 (64%); 82 (19%); 71 (17%)134 (57%); 57 (24%); 43 (19%)0.2Karnofsky PS ≥90%314 (75%)162 (72%)0.3Cell source: PB; BM386 (90%); 45 (10%)205 (88%); 29 (12%)0.4Conditioning: RIC; MAC193 (45%); 238 (55%)99 (42%); 135 (58%)0.5Additional ATG use126 (29%)75 (32%)0.4 [ [O177 Table] 1 . Table 1. Population description] Disclosure: Nothing to declare O178 Myeloablative conditioning for first allogeneic HSCT in pediatric all: FTBI or chemotherapy? - An update of the retrospective multicenter EBMT-PDWP studyAndre Manfred Willasch1, Christina Peters2, Petr Sedlacek3, Jean-Hugues Dalle4, Vassiliki Kitra-Roussou5, Akif Yesilipek6, Jacek Wachowiak7, Arjan Lankester8, Arcangelo Prete9, Amir Ali Hamidieh10, Marianne Ifversen11, Jochen Buechner12, Gergely Krivan13, Rose-Marie Hamladji14, Cristina Diaz de Heredia15, Elena Skorobogatova16, Gerard Michel17, Franco Locatelli18, Alice Bertaina19, Paul Veys20, Sophie Dupont21, Reuven Or22, Tayfun Güngör23, Olga Aleinikova24, Sabina Sufliarska25, Mikael Sundin26, Jelena Rascon27, Ain Kaare28, Damir Nemet29, Franca Fagioli30, Thomas Erich Klingebiel1, Jan Styczynski31, Marc Bierings32, Kalman Nagy33, Manuel Abecasis34, Boris Afanasyev35, Marc Ansari36, Kim Venntenranta37, Amal Alseraihy38, Alicja Chybicka39, Stephen Robinson40, Yves Bertrand41, Alphan Kupesiz42, Ardeshir Ghavamzadeh43, Antonio Campos44, Arnaud Dalissier45, Myriam Labopin46, Selim Corbacioglu47, Jaques Emmanuel Galimard45, Peter Bader1 1 Goethe University Frankfurt, Frankfurt am Main, Germany, 2 St Anna Children's Hospital, Vienna, Austria, 3 University Hospital Motol, Prague, Prague, Czech Republic, 4 Hôpital Robert Debré and Paris-Diderot University, Paris, France, 5 Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece, 6 Bahcesehir University, Istanbul, Turkey, 7 University of Medical Sciences, Poznan, Poland, 8 Leiden University Medical Center, Leiden, Netherlands, 9 University of Bologna, Bologna, Italy, 10 Tehran University of Medical Sciences, Hematology-Oncology and Stem Cell Transplantation Research Center, Teheran, Iran, Islamic Republic of, 11 Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, 12 Oslo University Hospital Rikshospitalet, Oslo, Norway, 13 United St. Istvan and St. László Hospital, Budapest, Hungary, 14 Service Hématologie Greffe de Moelle, Centre Pierre et Marie Curie, Alger, Algeria, 15 Hospital Universitario Vall d'Hebron, Barcelona, Spain, 16 Russian Children's Hospital, Moscow, Russian Federation, 17 Timone Enfants Hospital, AP-HM and Aix-Marseille University, Marseille, France, 18 IRCCS Ospedale Pediatrico Bambino Gesù, Università di Pavia, Rome, Italy, 19 Stanford University Medical Center, Stanford, CA, United States, 20 NHS Foundation Trust, Great Ormond Street Hospital for Children, London, United Kingdom, 21 Cliniques Universitaires Saint-Luc, Brussels, Belgium, 22 Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 23 University Children's Hospital, Children`s Research Center (CRC), Zurich, Switzerland, 24 Republic Clinical Research Centre, Minsk, Belarus, 25 Comenius University Medical School, Limbová, Bratislava, Slovakia, 26 Astrid Lindgren Children's Hospital, Karolinska University Hospital, Pediatric Blood Disorders, Immunodeficiency and Stem Cell Transplantation, Stockholm, Sweden, 27 Affiliate of Vilnius University Hospital Santariskiu Klinikos, Center of Pediatric Oncology and Hematology, Children's Hospital, Vilnius, Lithuania, 28 Tartu University Hospital, Tartu, Estonia, 29 University Hospital Centre, Internal Clinic, Zagreb, Croatia, 30 Regina Margherita Children's Hospital, City of Science and Health of Turin, Turino, Italy, 31 Nicolaus Copernicus University Torun, Collegium Medicum, Bydgoszcz, Poland, 32 University Medical Centre Utrecht Pediatrics, Urecht, Netherlands, 33 Child Welfare Center, Borsod County Teaching Hospital, Miskolc, Hungary, 34 Instituto Portugues Oncologia, Lisboa, Portugal, 35 Saint Petersburg State Medical I.P. Pavlov University, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Haematology and Transplantation, Saint Petersburg, Russian Federation, 36 Geneva University Hospital, Geneva, Switzerland, 37 University of Helsinki, Hospital for Children and Adolescents, Helsinki, Finland, 38 King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia, 39 Wroclaw Medical University, Cape of Hope Medical Center, Wroclaw, Poland, 40 NHS Foundation Trust, University Hospitals Bristol, Bristol, United Kingdom, 41 IHOP and Claude Bernard University, Lyon, France, 42 Akdeniz University, School of Medicine, Antalya, Turkey, 43 Shariati Hospital, Hematology-Oncology and BMT Research, Teheran, Iran, Islamic Republic of, 44 Portuguese Institute of Oncology, Porto, Portugal, 45 EBMT Paediatric Diseases Working Party, Paris, France, 46 EBMT Paris Study Office, Paris, France, 47 University of Regensburg, Regensburg, Germany Background: It is still a matter-of-debate if chemotherapy (CHT) can replace fractionated total-body-irradiation (fTBI) in myeloablative conditioning (MAC) for allo-HSCT in pediatric ALL. We hereby present the latest update of this international multicenter EBMT-PDWP-study (Blood 2017, 130(Suppl. 1):911). Methods: This update was done to extend the time of follow-up (FU, date of analysis: 01/OCT/2018). To compare outcomes of fTBI vs CHT-conditioning, we performed a retrospective EBMT-registry study. Children aged 2-18 years (y) after MAC for first allo-HSCT of BM/PBSC from MSD/UD in CR1/CR2 between 2000-2012 were included. Propensity-score-weighting was used to control pretreatment imbalances of observed variables. This statistical method ensured that analyzed groups differed only in the parameter under investigation (here: conditioning). Results: In total 3054 pts (CR1: 1498 (49%), CR2: 1556 (51%)) were included. CR1: 1041 pts (69%) received BM and 457 pts (31%) PBSC from MSD (756 (50%)) or UD (742 (50%)). CR2: 1064 pts (68%) received BM and 492 pts (32%) PBSC from MSD (672 (43%)) or UD (884 (57%)). Overall, conditioning was fTBI- in 2630 (86%) and CHT-based in 424 pts (14%). Busulfan/Cyclophosphamide/Etoposide (Bu/Cy/Eto) was the most frequently applied CHT-regimen in CR1 (66 (31%)) and Bu/Cy in CR2 (68 (32%)). The remaining conditionings included 5 combinations (other-chemo). 1498 pts in CR1 were conditioned with fTBI (1285), Bu/Cy/Eto (66) or other-chemo (147) with median-FU of 6.9, 6.2 and 4.5 y. In weighted univariate analysis, 5-y-OS was 68.8% after fTBI, 75.6% after other-chemo and 81.4% after Bu/Cy/Eto. In weighted Cox-model, taking into account the center-effect, pts having received Bu/Cy/Eto had a lower risk to experience an event compared to fTBI (HR=0.53, P=.029). 5-y-LFS (range: 58.4% (other-chemo) to 72.6% (Bu/Cy/Eto)), 5-y-RI (range: 17.1% (Bu/Cy/Eto) to 31.8% (other-chemo)) and 5-y-NRM (range: 9.8% (other-chemo) to 13.8% (fTBI)) did not show significant differences in weighted Cox-model. 1556 pts in CR2 were conditioned with fTBI (1345), Bu/Cy (68) or other-chemo (143) with median-FU of 6.2, 5.2 and 5.8 y. In weighted univariate analysis, 5-y-OS was 31.1% after other-chemo, 43.5% after Bu/Cy and 58.8% after fTBI. In weighted Cox-model, pts having received other-chemo had a higher risk to experience an event compared to fTBI (HR=2.00, P=< .0001). 5-y-LFS was 25.2% after other-chemo, 32.4% after Bu/Cy and 53.7% after fTBI. In weighted Cox-model, children having received Bu/Cy and other-chemo had a higher risk to experience an event compared to fTBI (HR=1.78, P=.005; HR=1.92, P< .0001). 5-y-RI was 30.6% after fTBI, 49.3% after BuCy and 53.7% after other-chemo. In weighted Cox-model, pts having received Bu/Cy and other-chemo had a higher risk to experience an event compared to fTBI (HR=2.06, P=.006; HR=2.13, P< .0001). 5-y-NRM (range: 18.3% (BuCy) to 21.1% (other-chemo)) did not show significant differences in weighted Cox-model. Conclusions: This recent study-update ensured a substantial FU. We confirmed the clear superiority of fTBI-conditioning compared to CHT with regard of LFS and RI for ALL-pts undergoing allo-HSCT in CR2. For pts in CR1 we could not find significant differences between fTBI and CHT-conditioning. These retrospective findings are currently re-evaluated in the prospective, randomized, international trial (ALL-SCTped-2012-FORUM). Disclosure: Nothing to declare. O179Abstract already published.O180 Effective cancer immunotherapy with ERBB2-CAR-engineered cytokine-induced killer (CIK) cells in high-risk soft tissue sarcomasMichael Merker1, Juliane Wagner1, Vida Meyer1, Evelyn Ullrich1, Thomas Klingebiel1, Winfried S. Wels2, Peter Bader1, Eva Rettinger1 1 University Hospital Frankfurt, Frankfurt, Germany, 2 Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt, Germany Background: Pediatric patients with high-risk alveolar rhabdomyosarcoma (aRMS) above the age of 10 years cannot be cured by conventional therapies. Immune cells targeting ErbB2 with a chimeric antigen receptor (CAR) were recently considered for these patients. Cytokine-induced killer (CIK) cells already capable of natural killer (NK)-like anti-tumor capacity additionally redirected with an ErbB2 CAR may provide overall disease control in these high-risk tumors. Methods: ErbB2-CAR modified CIK cells were generated from conventional CIK cells (WT-CIK) by lentiviral gene transduction on day 4 of culture. The codon-optimized CAR sequence consists of an IgG heavy-chain signal peptide, an ErbB2-specific antibody fragment scFv (FRP5) and a modified CD8α hinge region, as well as CD28 transmembrane and intracellular domains and a CD3ζ intracellular domain. 1x105 luciferase gene-transduced RH30 (aRMS) cells were engrafted in immunodeficient NOD/SCID/γc-(NSG) mice. Mice were randomly selected into 5 different treatment groups (DBPS on day +1, 2.5x106 WT-CIK or ErbB2 CAR-CIK cells on days +1 and +36, 2.5x106 WT-CIK or ErbB2 CAR-CIK cells on days +22 and +57). Mice were monitored by bioluminescence imaging (BLI) until day +100. Tumor engraftment and immune cell homing at tumor sites were analyzed by FACS, chimerism and immunohistochemistry analyses. Results: Human RMS xenografts were established in all mice treated with DBPS only. Control-mice showed a median survival of 62 days. Human RMS was identified in all analyzed organs, with the highest tumor burden seen in livers of DBPS-treated mice. Mice injected with WT or ErbB2-CAR CIK cells on days +1 and +36 showed a significant improved (p < 0.014 and p < 0.01) disease-free survival, respectively. Furthermore, no signs of tumor engraftment were shown by BLI in ErbB2 CAR-CIK cell treated mice while some of the mice treated with WT-CIK cells developed positive tumor signals between weeks 7 and 10. In 4 out of 6 (64%) WT- and in all (8 of 8, 100%) CAR-CIK cells treated mice no residual tumor cells were identified by PCR-based analysis. In contrast, tumor cells were detectable in all mice with delayed anti-tumor treatment applied on day +22 and +57. However, tumor growth was lower in these groups. Correspondingly, BLI showed delayed tumor engraftment in mice with WT- and even more with CAR-CIK cell treatment given on day 22. Treatment on day 22 resulted in a significantly improved survival of ErbB2-CAR CIK cell treated mice (p < 0.01), while survival was not improved after WT-CIK cell infusion (p > 0.07). Within all treatment groups, immune cells were detected by chimerism and FACS analyses. FACS analyses showed a significant increase of NK-like T cells (p < 0.01 and < 0.05, WT- and ErbB2-CAR CIK cells). Additionally, a higher, but not significant, amount of effector memory and stem cell memory T cells were detected. Conclusions: These pre-clinical in vivo results indicate that ErbB2- CAR redirection of CIK cells improves both homing and NK-like cytotoxicity of CIK cells in the presence of ErbB2-positive tumors, implying that this therapy may represent a step forward in the treatment of patients with resistant, relapsed and advanced RMS. Disclosure: Michael Merker, Juliane Wagner, Vida Meyer, Thomas Klingebiel, Winfried S. Wels and Eva Rettinger have nothing to declare. Peter Bader declares the following potential conflicts of interest: Novartis (consultancy: included expert testimony, speaker bureau, Honoraria), Medac (Research Funding, Patents and Royalties), Riemser (Research Funding), Neovii (Research Funding), Amgen (Honoraria). O181 Genesis - a phase III randomized double-blind, placebo-controlled trial, evaluating safety and efficacy of BL-8040 and G-CSF in mobilization of HCS’S for autologous transplantation-multiple myelomaHemda Chen1, Zachary D. Crees2, Keith Stockerl-Goldstein K2, Abi Vainstein1, Ella Sorani1, Osnat Bohana-Kashtan1, John F Dipersio2 1 BiolineRx, Tel Aviv, Israel, 2 Washington University in St. Louis, St. Louis, WA, United States Background: CXCR4 mediates retention of hematopoietic stem cells (HSCs) in the bone marrow (BM) niche. BL-8040, a novel, high affinity CXCR4 antagonist is a potent mobilizer of HSCs to the peripheral blood with numerous potential clinical applications, including mobilization of CD34+ cells for autologous HSC transplantation (auto-HSCT) in Multiple Myeloma (MM). This study aims to evaluate the efficacy of single dose BL-8040 plus G-CSF in mobilization of ≥6.0x106 CD34+ cells/kg in up to 2 apheresis sessions for auto-HSCT in MM. Methods: A Phase III study composed of an open-label, single-arm lead-in Part1 followed by a randomized, double-blinded, placebo-controlled Part2. Eligible MM patients age 18-78 will receive G-CSF (10 µg/kg; SC) daily for up to 8 days and one dose of BL-8040 (1.25 mg/kg; SC) or placebo on day 4 followed by up to 2 apheresis sessions; and if needed a second dose of BL-8040 or placebo on day 6 followed by up to 2 apheresis sessions. Part1 included up to 3 cohorts (~10 patients/cohort), with Data Monitoring Committee (DMC) review after each cohort. Part2 will include 177 patients randomized 2:1. Results: Part1 enrolled 11 patients, median age 61 (57-70). 9/11 patients (82%) reached the primary endpoint of ≥6x106 CD34+ cells/kg with one dose of BL-8040 and up to 2 apheresis sessions. 7/11 patients (64%) collected ≥6x106 CD34+ cells/kg in one apheresis session. Administration of BL-8040 resulted in a 7.86-fold average increase in circulating peripheral CD34+ cells (range 1.62-15.75, median 7.5, n=9). Additional CD34+ immunophenotyping/subset analyses are currently underway. BL-8040 plus G-CSF was found to be safe and well tolerated. Following these promising results, DMC recommended early continuation to Part2 of the Phase III trial. Conclusions: The GENESIS lead-in results demonstrate BL-8040 is a potent mobilizer of HSCs, with potential to improve mobilization rates while minimizing mobilization-related healthcare costs. Clinical Trial Registry: NCT03246529 Disclosure: Hemda Chen -Medical Director, BiolineRx Abi Vainstin - VP of medical affairs, BiolineRx Ella Sorani- VP of R&D, BiolineRx Osnat Bohana-Kashtan- project manager, BiolineRx John F. DiPersio - consultant for BiolineRx O182 Real life experience in the treatment of pediatric, adolescent and young adult all patients using commercially available CAR-T-cellsPeter Bader1, Jan Soerensen1, Eva Rettinger1, Andre Willasch1, Anne Sonntagbauer1, Sümmeyye Elgaz1, Franziska Kalensee1, Hermann Kreyenberg1, Marc Ansari2, Christine Wolschke3, Richard Noppeney4, Gunnar Cario5, Guido Kobbe6, Tobias Feuchtinger7, Marion Subklewe8, Thomas Klingebiel1, Martin Hutter1, Evelyn Ullrich1, Halvard Bönig9, Sabine Huenecke1, Andrea Jarisch1 1 University Hospital Frankfurt, Frankfurt, Germany, 2 Geneva University Hospital, Children and Adolescents, Geneva, Switzerland, 3 Universitsklinik Hamburg Eppendorf, Hamburg, Germany, 4 University Hospital Essen, Essen, Germany, 5 University Medical Center Schleswig-Holstein, Kiel, Germany, 6 University Medical Center Düsseldorf, Düsseldorf, Germany, 7 LMU, von Hauner Kinderspital, Munich, Germany, 8 University Hospital Munich, Munich, Germany, 9 German Red Cross Blood Center Frankfurt and Institute of Transfusion Medicine and Immunohematology, Frankfurt, Germany, Background: Children, adolescents and young adult patients with ALL with second relapse, relapse after allogeneic SCT or patients with primary refractory disease have a poor prognosis with conventional treatment concepts. In this patient group several studies using second generation CD19 chimeric antigen receptor T- cells (CAR-T cells) demonstrated high efficacy with two year survival rates of up to 65%. Recently, two different CAR-T cell products were approved by the FDA and in 2018 also by the EMA in Europe: Tisagenlecleucel (Kymriah®) for the treatment of patients with B-precursor ALL who are i) refractory, ii) in second relapse or iii) who relapsed after allogeneic SCT (relapsed/refractory ALL; r/r ALL) as well as for diffuse large cell lymphoma (DLBCL) and Axicabtagen Ciloleucel (Yescarta®) for the treatment of B-cell lymphoma. Here we report our first results using commercially available CAR-T-cell product Tisagenlecleucel (Kymriah®) in patients with ALL which were treated by the University Hospital for Children and Adolescents Frankfurt am Main (n=9), the Department of Medicine III, University Hospital LMU Munich (n=1), and the von Hauner Kinderspital, LMU Munich, Germany (n=1). Methods: Between October and December 2018 eleven patients received apheresis for CAR-T cell generation. Nine patients suffered from r/r c-ALL, and two from r/r B-precursor ALL. Eight patients had relapsed after allogeneic HSCT, one patient each suffered from first r/relapse, second r/relapse or from primary r/ALL. In 9/11 (82%) patients CAR-T cell production was successful after one and in 2 patients (18%) after a second apheresis. Median patients' age was 16.7 years (1.1-25.4). Between apheresis and start of lymphodepleting chemotherapy (LDC), 10/11 patients received low dose chemotherapy according to the FRAPOSTALL protocol (Willasch et al. 2016) and one patient was treated with inotuzumab. Production slots were immediately available, resulting in turn-around-time from apheresis to product delivery of 3-4 weeks. Disease status at start of LDC was CR w/o MRD (n=4), CR MRD pos. (n=2), CRi (n=1), persistence of blasts (n=2), and disease progression (80-100% blasts, n=2). LDC consisting of FLU-CYC was given to 9/10 patients, one patient did not receive LDC. Results: CAR-T cells could be transfused to 10/11 patients at a median dose of 1.5 Mio/kgBW (0.145 Mio 8.5). In one patient, in whom a second viral transduction procedure was necessary; neither LDC nor CAR-T cell transfusion could be given because of diseases progression and deterioration of the patient's general condition. Cytokine release syndrome (CRS) grade I was observed in one patient; 8/10 patients did not develop CRS. Cytokine related encephalopathy syndrome (CRES) grade II was observed in 1/10 patients. At day +28 8/10 patients (80%) achieved MRD negative CR. The two patients with progressive disease at time of LDC did not respond although CAR-T cells could be seen morphologically under the microscope. This might be explained by multidrug related phenomenon protecting refractory leukemia from CAR-T cell attack. Conclusions: Commercial available CAR-T cell product Tisagenlecleucel (Kymriah®) showed high efficacy in r/r-ALL patients to re-induce CR. Clinical Trial Registry: Commercial available CAR-T cell product Tisagenlecleucel (Kymriah®) showed high efficacy in r/r-ALL patients to re-induce CR. Disclosure: PB: Novartis (consultancy: included expert testimony, speaker bureau, Honoraria); Medac (Research Funding, Patents and Royalties); Riemser (Research Funding); Neovii (Research Funding); Amgen (Honoraria). AJ: Novartis and Bluebird: (Consultancy). All other author declare no COI.
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