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359 Treatment Guided By Next Generation Functional Drug Screening Provides Clinical Benefit in Advanced Aggressive Hematological Malignancies: Final Evaluation of the Open Label, Single Arm Exalt Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 803. Emerging Diagnostic Tools and Techniques I
Hematology Disease Topics & Pathways:
Adult, Diseases, Non-Biological, Therapies, Combinations, Lymphoid Malignancies, Study Population, Myeloid Malignancies, Clinically relevant
Sunday, December 6, 2020: 9:30 AM

Christoph Kornauth1*, Tea Pemovska, PhD, MSc, BSc1,2*, Gregory Ian Vladimer, PhD3*, Günther Bayer4*, Michael Bergmann5*, Sandra Eder6*, Ruth Eichner2,7*, Harald Esterbauer, MD, PhD8*, Ruth Exner5*, Verena Felsleitner-Hauer9*, Maurizio Forte, MSc1*, Alexander Gaiger1*, Hildegard T. Greinix, MD10, Wolfgang Gstöttner11*, Marcus Hacker12*, Alexander Hauswirth, MD1*, Tim Heinemann13*, Daniel Heintel14*, Mir Ali Reza Hoda15*, Ulrich Jaeger, MD1,16, Lukas Kazianka, MD1*, Lukas Kenner, MD4*, Barbara Kiesewetter, MD17*, Nikolaus Krall, PhD3*, Trang Le, BSc1*, Simone Lubowitzki1*, Marius E Mayerhoefer18,19*, Elisabeth Menschel20*, Olaf Merkel, PhD4*, Katsuhiro Miura, MD, PhD21*, Leonhard Muellauer, MD, PhD4*, Peter Neumeister, MD10*, Thomas Noesslinger, MD20, Katharina Ocko22*, Leopold Öhler23*, Michael Panny, MD20*, Alexander Pichler, MD1*, Edit Anna Porpaczy, MD1*, Gerald Prager, MD17*, Markus Raderer17*, Robin Ristl24*, Reinhard Ruckser, MD25, Julius Salamon26*, Ana-Iris Schiefer4*, Ann-Sofie Schmolke, MD1*, Ilse Schwarzinger, MD8*, Edgar Selzer27*, Cathrin Skrabs1*, Wolfgang R. Sperr, MD1*, Ismet Srndic, MSc2*, Renate Thalhammer, MD8*, Peter Valent, MD1,28, Emiel Van Der Kouwe1*, Katrina Vanura, PhD1, Stefan Vogt9*, Cora Waldstein27*, Dominik Wolf, Univ. Prof. Dr.29, Christoph Zielinski30*, Ingrid Simonitsch-Klupp, MD4*, Giulio Superti-Furga, PhD2*, Berend Snijder, PhD13* and Philipp B. Staber, MD, PhD1

1Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
3Allcyte, Vienna, Austria
4Department of Pathology, Medical University of Vienna, Vienna, Austria
5Department of Surgery, Medical University of Vienna, Vienna, Austria
6Department of Internal Medicine and Hematology/Oncology, Klinikum Klagenfurt, Klagenfurt, Austria
7Department of Medicine III, Technical University of Munich, Munich, Germany
8Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
9Department of Medicine and Oncology, LKH Wiener Neustadt, Wr. Neustadt, Austria
10Department of Internal Medicine, Division of Hematology, Medical University of Graz, Graz, Austria
11Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria
12Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
13Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland
14Division of Medicine I, Wilhelminenspital, Vienna, Austria
15Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
16Austrian Group Medical Tumor Therapy, Salzburg, Austria
17Department of Medicine I, Division of Oncology, Medical University Vienna, Vienna, Austria
18Dept. of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria
19Department of Radiology, Memorial Sloan Kettering Cancer Center, New York
203rd Medical Department, Hematology & Oncology, Hanusch Hospital, Vienna, Austria
21Nihon university school of medicine, Tokyo, Japan
22Pharmacy Department, Vienna General Hospital, Vienna, Austria
23Internal Medicine I, Department of Oncology, St. Josef Hospital, Vienna, Austria
24Section for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria
252. Medical Department, SMZ Ost, Vienna, Austria
26Department of Medicine, Landesklinikum Waidhofen a.d. Ybbs, Waidhofen-Ybbs, Austria
27Department of Radiation Oncology, Medical University Vienna, Vienna, Austria
28Ludwig Boltzmann Institute for Hematology and Oncology, Vienna, Austria
29Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Austria
30Vienna Cancer Center, Medical University of Vienna, Vienna, Vienna, Austria


Aggressive hematological malignancies in relapsed/refractory setting bear a dire prognosis with low cure rates and short survival. Matching these patients to therapies is challenged by complexity due to spatial and temporal tumor evolution and incomplete understanding of genotype to phenotype correlations. Direct functional testing could address these impediments. The EXALT trial is an interventional, one-arm study designed to assess the clinical value of next generation functional drug screening (ngFDS). An interim analysis on 17 patients suggested a clinical benefit (Snijder et al., Lancet Hematol. 2017).


We applied image-based ngFDS to quantify differential ex-vivo sensitivity of primary patient tumor cells to respective non-tumor cells towards 136 small molecule drugs, including EMA approved for any indication or experimental. We screened bone marrow, peripheral blood or lymph node material from 143 patients who suffered from late stage aggressive hematological malignancies (acute leukemias, aggressive B- and T-cell lymphomas) , discussed the results in a multidisciplinary tumor board and recommended treatments to physicians (A). The primary endpoint of this study was the percentage of patients reaching a PFS-ratio (PFS(ngFDS treatment)/PFS(previous treatment)) of ≥1.3 with an H0 hypothesis < 15% patients. The secondary endpoint was overall response rate (ORR) defined as proportion of patients reaching complete remission (CR) or partial remission (PR). Additionally, we performed a post hoc analysis to evaluate the matching of ngFDS to drugs used in actual treatment (matching score of received treatment).


56 (39%) patients were evaluable and treated according to ngFDS based recommendations. With 30 of 56 (54%) ngFDS guided patients experiencing a PFS ratio of ≥1.3, the primary study endpoint was reached. 11 patients (37%) had ongoing response at censoring date (B). The median follow-up was 718 days. The median number of days from sampling to treatment was 21 (range 4-77). The ngFDS treatment regimens consisted of a median of 2 drugs (range: 1-6). ORR was 55% for all evaluable ngFDS treated patients, 60% for the lymphoid subgroup and 41% for the myeloid subgroup. Patients on ngFDS guided treatment with performance status ECOG ≤ 1 had a median PFS of 207 days compared to a median PFS of 29 days for patients with higher ECOG (p < 0.001, C). 24 of 39 (62%) patients with ECOG ≤ 1 had a PFS ratio of ≥1.3 (D). In disease specific subgroup analysis median PFS of T-cell lymphoma patients was 235 days versus 60 days for B-cell lymphoma patients (p = 0.018, E). Age (≤60 vs. >60), sex, lineage (myeloid vs. lymphoid), number of previous treatment lines (≤2 vs. >2), and clinical presentation (leukemia vs. lymphoma) did not have an impact on PFS of ngFDS guided treatment. Post hoc analysis including additional 17 non-ngFDS treated patients demonstrated that only patients receiving treatment with a positive ngFDS matching score demonstrated clinical benefit (HR: 0.53, p=0.005; vs. HR: 1.4, p=0.4). ngFDS matched treatments resulted in higher PFS for patients with tumor samples that had a cancer cell fraction of 10-50% in comparison to patients with samples of lower or higher cancer cell percentage (HR:0.35, p=0.01).


ngFDS could be integrated in the routine clinical work flow. ngFDS guided treatments led to high rates of PFS prolongation compared to previous treatments of individual patients. ngFDS guided treatment is feasible and effective in patients with late stage aggressive hematological malignancies. These results prompted a prospective randomized trial comparing treatment guidance based on ngFDS or comprehensive genomic profiling or physician’s choice (EXALT-2 trial, NCT04470947).

Disclosures: Vladimer: Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Jaeger: Karyopharm: Honoraria; Amgen: Honoraria; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; True North: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding; F. Hoffmann-La Roche: Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria. Krall: Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Valent: Allcyte GmbH: Research Funding; Cellgene: Honoraria, Research Funding; Pfizer: Honoraria. Wolf: Celgene: Honoraria, Research Funding. Zielinski: MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Imugene: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Merrimack: Consultancy, Honoraria, Speakers Bureau; Merck KGaA: Consultancy, Honoraria, Speakers Bureau; Fibrogen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Tesaro: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Speakers Bureau; Athenex: Consultancy, Honoraria, Speakers Bureau. Superti-Furga: Allcyte GmbH: Current equity holder in private company, Other: Founder. Snijder: Allcyte GmbH: Current equity holder in private company, Other: Founder. Staber: Roche: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Celgene/ BMS: Consultancy, Honoraria; msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.

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