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P134 (0156) INDUCTION THERAPY WITH EVEROLIMUS IN COMBINATION WITH DHAP (DEXAMETHASONE, HIGH-DOSE ARAC, CISPLATINUM) IN PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA

A RANDOMIZED, PLACEBO-CONTROLLED PHASE I/II TRIAL (HD-R3I)

doi: 10.1097/01.HS9.0000547977.84027.90
Relapsed/Refractory HL

Bastian von Tresckow, Andreas Hüttman, Vladan Vucinic, Horst Müller, Annette Pluetschow, Andreas Viardot, Max S. Topp, Carsten Kobe, Boris Böll, Dennis A. Eichenauer, Stephanie Sasse, Heinz Haverkamp, Michael Fuchs, Andreas Engert and Peter Borchmann

German Hodgkin Study Group (GHSG), University Hospital of Cologne, Germany, Universitätsklinik Essen, Klinik für Hämatologie / WTZ Ambulanz, Universitätsklinik Leipzig, Medizinische Klinik II, Hämatologie, Universitätsklinikum Ulm, Innere Abteilung III, Universitätsklinikum Würzburg, Zentrum Innere Medizin, Institute of Medical Statistics and Bioinformatics, University of Cologne

Background: Induction chemotherapy followed by BEAM high dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSC transplant) is standard of care for transplant-eligible patients with relapsed or refractory classical Hodgkin lymphoma (rrHL). However, approx. 50% of patients relapse and therefore, this strategy must be improved. As response to induction therapy is predictive of the outcome after HDCT, this trial aimed at improving the response to induction therapy by adding oral everolimus to time-intensified standard DHAP (Ever-DHAP).

Methods: We included patients with histologically confirmed rrHL aged 18–60 years in this phase I/II trial. Dosage of everolimus was pre-determined in the phase I part with 10 mg/day given parallel to DHAP for 14 days within each of two cycles. The phase II part started as a randomized controlled trial comparing 50 patients in the everolimus group to 50 patients in a placebo group. The primary endpoint of the phase II part was the CT-based complete remission (CR-) rate after two cycles of Ever-DHAP. This CR-rate would be expected to be ≥ 40% if adding everolimus was effective. Secondary endpoints of the trial were PET-based CR-rate after two cycles of induction, progression-free and overall survival as well as to recovery, adverse events, duration of induction therapy, discontinuation rates and rates of successful PBSC collection. The trial was registered at ClinicalTrials.gov with ID NCT01453504.

Results: From 7/2014 to 3/2018 we recruited a total of 59 patients in the phase II part. Because of poor recruitment the placebo group was closed in 9/2015 after 9 patients were randomized. Of 50 patients in the everolimus group 2 did not start therapy; 3 additional patients discontinued Ever-DHAP because of toxicity. PBSC collection was successful in 37/39 documented patients receiving Ever-DHAP (95%). After two cycles of therapy we observed a CT-based CR in 12/45 patients of the everolimus group (27%) and in 2/9 patients of the placebo group (22%). A PET-based CR was reached by 19/38 patients of the everolimus group (50%) and by 4/5 patients of the placebo group. In the everolimus group 2 patients had refractory disease (4%) and 2 died (4%), 3 and 4 months after starting but not related to Ever-DHAP. Final results will be presented at the symposium.

Conclusion: Adding everolimus to time-intensified DHAP is feasible, however, the Ever-DHAP regimen failed to show an improved efficacy.

Copyright © 2018 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.