CLLM1-PROTOCOL OF THE GERMAN CLL-STUDY GROUP (GCLLSG)

Transkript

1 CLLM1-PROTOCOL OF THE GERMAN CLL-STUDY GROUP (GCLLSG) Screening supported by a central review allows a precise selection of the population for maintenance therapy within the CLLM1 trial of the German CLL Study Group Anne Westermann, DCLLSG, Uniklinik Köln, DKK 1

2 Approach: individualized CLL therapy Personalized treatment plan tailored to patients needs and diagnosis. Staging Lymphocyte doubling time Response to treatment Molecular cytogenetics 17p-Deletion, TP53 Mutation,. Physical fitness Go go slow go No go Patient-specific treatment comorbidities, renal function + CLL-specific treatment Molecular cytogenetics, Lymphocyte doubling time, Serum thymindine kinase MRD Intensify therapy if MRD+ Maintenance therapy?

3 OUTCOME CLL8 TRIAL PFS according to TP 53 PFS according to 17p 3

4 OUTCOME CLL8 TRIAL PFS according to MRD PFS according to IGHV 4

5 RATIONALE OF CLLM1 Patients with high risk of early PD after Firstline have short survival no standard treatment options few patients are eligible for stem cell transplantion Why Lenalidomide? effective and approved for treatment of relapsed and refractory multiple myeloma ensures recovery of T-cell defects direct CD8+ T-cell killing of B-CLL cells 5

6 DEFINITION OF HIGH RISK High MRD level 10-2 or Median MRD level <10-2 combined with at least one of the following del(17p) TP53 mutation unmutated IGHVstatus 6

7 CLLM1-STUDY DESIGN Physically fit and previously untreated patients with treatment requiring disease 700 screening patients High Risk Firstline investigator s choice (FCR, BR, FR (FC) High Risk 2: 1 Rando 200 randomized patients L maintenance placebo Treatment up to PD

8 CLLM1 TRIAL Risk assessments performed within 8 to 13 months Up to 6 months prior to Firstline therapy 4 6 months firstline therapy 2 5 months after end of last cycle Central lab results of TP53, 17p, IGHV Firstline Therapy Mandatory MRD Analysis in Kiel Complete or incomplete local results of TP53, 17p, IGHV Risk Assessment: Patients with low risk Patients with high risk

9 MEDICAL REVIEW Patient data are checked by GCLLSG Physicians Fit patients: CIRS<6 Response to Firstline Renal function: Crea-clearance > 60ml/min Exclusion of active Infection/Hematoxicity 9

10 REASONS FOR PATIENT S WITHDRAWAL 10

11 PATIENTS DROP OUT/ LOW RISK 442 Registered patients Firstline Therapy 162 Pts screened after firstline 32 Drop outs 69 Drop outs 123 Pts with low risk 34 Pts randomized 11

12 REASONS FOR DROP OUT 1 patient s Decision 2 other disease 3 no adequate firstline therapy 4 treatment related reasons 12

13 REASONS FOR PATIENT S WITHDRAWAL SURVEY DECEMBER tired of treatment 2 afraid of lenalidomide side effects 3 concerned of frequent visits 13

14 CONCLUSION Maintenance therapy after a careful selection of a subgroup with high risk is feasible if Patients and doctors are convinced of the study drug and the benefits of maintenance therapy 14

15 Thank you! Prof. Martin Dreyling, München; Dr. Ingo Ringshausen, München; Dr. Sebastian Böttcher, Kiel; Dr. Cordelia Steinbrecher, Erfurt; Dr. Jan Dürig, Essen; Prof. Thorsten Zenz, Heidelberg; Prof. Michael Pfreundschuh, Homburg/Saar; Dr. Barbara Eichhorst, Köln; Dr. Florian Heidel, Magdeburg; Dr. Martin R. Müller, Tübingen; Dr. Peter Staib, Eschweiler; Dr. Jochen Pfirstinger, Regensburg; Prof. Lothar Bergmann, Frankfurt; Dr. Matthias Port, Hannover; Prof. Christian Andreas Schmidt, Greifswald; Prof. Stephan Stilgenbauer, Ulm; Dr. Kordelia zur Hausen, Aachen; Dr. Karin Heinisch, Lemgo; Prof. Clemens-M. Wendtner, München; Dr. Otto Prümmer, Kempten; Dr. Peter Reimer, Essen; Dr. Beate Schultheis, Herne; Prof. Matthias Zeis, Hamburg; Dr. Elisabeth Lange, Hamm; Dr. Heinz A. Dürk, Hamm; Dr. Eva Roemer, Idar-Oberstein; Dr. Stefan Mahlmann, Kaiserslautern; Dr. Frank Heits, Rotenburg; Dr. Stefan Kremers, Lebach; Dr. Alexander Wacker, Reutlingen; Dr. Cornelia Winkelmann, Lutherstadt-Wittenberg; Dr. Marcus Hentrich, München; Prof. Holger Hebart, Mutlangen; Prof. Georg Maschmeyer, Potsdam; Dr. Heribert Stauder, Regensburg; Dr. Thomas Geer, Schwäbisch Hall; Dr. Rolf Mahlberg, Trier; Prof. Doris Kraemer, Oldenburg; Dr. Christoph Diekmann, Bremen; Prof. Claudio Denzlinger, Stuttgart; Dr. Ullrich Graeven, Mönchengladbach; Dr. Michael Flaßhove, Düren; Prof. Heinz-Gert Höffkes, Fulda; Prof. Bernd Hertenstein, Bremen; Prof. Martin Bentz, Karlsruhe; Dr. Walter Lindemann, Hagen; Dr. Barbara Günther, Düsseldorf; Dr. Henry Simon, Ostfildern; Dr. Ludwig Fischer von Weikersthal, Amberg; Dr. Tobias Gaska, Paderborn; Dr. Alexander Kröber, Regensburg; Prof. Markus Bangerter, Augsburg; Dr. Michael Josef Eckart, Erlangen; Dr. Alexander Schmittel, Berlin; Dr. Philipp Kiewe, Berlin; Dr. Ulrich von Grünhagen, Cottbus; Dr. Thomas Illmer, Dresden; Dr. Robert Rohrberg, Halle; Dr. Ursula Vehling-Kaiser, Landshut; Doris Fleckenstein, München; Dr. Burkhard Schmidt, München; Dr. Rudolf Schmits, Saarbrücken; Dr. Martina Stauch, Kronach; Dr. Sebastian Müller, Ansbach; Dr. Ali Aldaoud, Leipzig; Dr. Holger Nückel, Bochum; Dr. Ulrike Söling, Kassel; Dr. Ulla von Verschuer, Essen; Dr. Hartmut Linde, Potsdam; Dr. Stefan Fronhoffs, Siegburg; Dr. Michael Sandherr, Weilheim; Dr. Daniel Reschke, Oldenburg; Dr. Thomas Decker, Ravensburg; Dr. Jörg Thomalla, Koblenz; Dr. Tobias Reiber, Freiburg; Dr. Christina Balser, Marburg; Dr. Rudolf Schlag, Würzburg; Dr. Ekkehart Ladda, Neumarkt; Prof. Stephan Schmitz, Köln; Dr. Claus-Christoph Steffens, Stade; Dr. Herbert Lebahn, Berlin; Dr. Kathleen Jentsch-Ullrich, Magdeburg; Dr. Hans-Peter Böck, Offenbach; Prof. Michael Koenigsmann, Hannover; Dr. Robert Eckert, Wendlingen; Dr. Oswald Burkhard, Worms; Dr. Richard Hansen, Kaiserslautern; Dr. Sigrun Müller-Hagen, Hamburg; Dr. Georg Schliesser, Gießen; Dr. Volkmar Böhme, Hamburg; Dr. Helmut Forstbauer, Troisdorf; Dr. Martin Teich, Chemnitz; Dr. Georg Köchling, VS-Villingen; Dr. Volker Lakner, Rostock; Steffen Dörfel, Dresden; Dr. Martine Klausmann, Aschaffenburg; Dr. André Lollert, Krefeld; Prof. Wolfgang Knauf, Frankfurt/Main; Prof. Manfred Hensel, Mannheim; Dr. Stefan Fuxius, Heidelberg; Dr. Peter Schmidt, Neunkirchen; Dr. Lothar Müller, Leer; Jörg Seraphin, Northeim; Dr. Lars Scheuer, Speyer; Dr. Roland Repp, Bamberg; Dr. Felix Marquard, Celle; Dr. Gerold Baake, Pinneberg; Dr. Michael Rieger, Darmstadt; Dr. Holger Schulz, Frechen; Dr. H.W. Tessen, Goslar; Dr. Godehard Obst, Burgwedel; Prof. Walter Verbeek, Bonn; Dr. Hans Reinel, Schweinfurt; Dr. Johannes Mohm, Dresden; Dr. Hanns Detlev Harich, Hof; Prof. Kai Uwe Chow, Frankfurt am Main; Dr. Ali-Nuri Hünerlitürkoglu, Neuss; Dr. Marcel Reiser, Köln; Prof. Michael Kiehl, Frankfurt an der Oder; Dr. Ulrike Enser-Weis, Bochum; Dr. Ute Kreiter, Mainz; Dr. Heike Steiniger, Oberhausen; Dr. Jan Schröder, Mülheim an der Ruhr; Dr. Uwe Sauer, Nordhorn; Dieter Mainka, Köln; Till-Oliver Emde, Recklinghausen; Dr. Matthias Egger, Lahr; Dr. Klaus Stengele, Singen; Prof. Jens Atzpodien, Georgsmarienhütte; Thomas Boldt, Freiberg