PMID- 32757230 OWN - NLM STAT- MEDLINE DCOM- 20210111 LR - 20210111 IS - 1099-1069 (Electronic) IS - 0278-0232 (Linking) VI - 38 IP - 5 DP - 2020 Dec TI - A phase 1 study to evaluate the feasibility and efficacy of the addition of ropeginterferon alpha-2b to imatinib treatment in patients with chronic phase chronic myeloid leukemia (CML) not achieving a deep molecular response (molecular remission 4.5)-AGMT_CML 1. PG - 792-798 LID - 10.1002/hon.2786 [doi] AB - The goal of current management of patients with chronic phase chronic myeloid leukemia (CML) is to reach treatment-free remission with sustained deep molecular remission (DMR) being the prerequisite therefor. Second-generation tyrosine kinase inhibitors can induce deeper and faster remission than imatinib, but are often associated with severe adverse events (AEs). The combination of pegylated interferon (IFN) with imatinib was shown to induce higher molecular remissions than imatinib alone in two studies. Treatment discontinuation rates due to IFN induced AEs were high in both studies. To investigate safety, tolerability (primary objective), and efficacy (secondary objective) of the combination of imatinib with ropeginterferon alpha-2b this phase I study was initiated. Twelve patients were planned to be enrolled. Nine patients completed the study according to protocol. Three patients terminated the study early, one due to occurrence of a dose-limiting toxicity (neutropenia grade 3), one due to an AE (panic attacks grade 2) and one due to the patient's decision. Tolerability was good, non-hematologic AEs were mainly grade 1/2, hematologic AEs were mainly neutropenias. No new AEs were reported for the combination of imatinib and ropeginterferon alpha-2b. In a nondose-dependent manner the addition of ropeginterferon alpha-2b led to the achievement of a DMR in four out of nine patients after a treatment duration of 18 months. The combination of imatinib and ropeginterferon alpha-2b is safe and showed in this phase I study the ability to deepen the molecular response in patients with chronic phase CML not achieving a DMR with imatinib alone. CI - (c) 2020 John Wiley & Sons Ltd. FAU - Heibl, Sonja AU - Heibl S AD - Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria. FAU - Buxhofer-Ausch, Veronika AU - Buxhofer-Ausch V AD - Department of Internal Medicine I with Hematology, Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria. AD - Medical Faculty, Johannes Kepler University Linz, Linz, Austria. FAU - Schmidt, Stefan AU - Schmidt S AD - Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria. FAU - Webersinke, Gerald AU - Webersinke G AD - Labor fur Molekulargenetische Diagnostik, Ordensklinikum Linz GmbH Barmherzige Schwestern, Linz, Austria. FAU - Lion, Thomas AU - Lion T AD - Labdia Labordiagnostik GmbH, Children's Cancer Research Institute, Vienna, Austria. FAU - Piringer, Gudrun AU - Piringer G AD - Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria. FAU - Kuehr, Thomas AU - Kuehr T AD - Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria. FAU - Wolf, Dominik AU - Wolf D AD - Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria. FAU - Melchardt, Thomas AU - Melchardt T AD - Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria. AD - Salzburg Cancer Research Institute, Center for Clinical Cancer and Immunology Trials (SCRI-CCCIT), Cancer Cluster Salzburg, Salzburg, Austria. FAU - Greil, Richard AU - Greil R AD - Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria. AD - Salzburg Cancer Research Institute, Center for Clinical Cancer and Immunology Trials (SCRI-CCCIT), Cancer Cluster Salzburg, Salzburg, Austria. FAU - Thaler, Josef AU - Thaler J AD - Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria. LA - eng GR - AOP Orphan Pharmaceuticals/ PT - Clinical Trial, Phase I PT - Journal Article DEP - 20200819 PL - England TA - Hematol Oncol JT - Hematological oncology JID - 8307268 RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (Recombinant Proteins) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 8A1O1M485B (Imatinib Mesylate) RN - G8RGG88B68 (peginterferon alfa-2b) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Drug Resistance, Neoplasm MH - Feasibility Studies MH - Female MH - Humans MH - Imatinib Mesylate/administration & dosage MH - Interferon alpha-2/administration & dosage MH - Interferon-alpha/administration & dosage MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*drug therapy/mortality MH - Male MH - Middle Aged MH - Polyethylene Glycols/administration & dosage MH - Recombinant Proteins/administration & dosage MH - Retreatment MH - Treatment Failure MH - Treatment Outcome OTO - NOTNLM OT - CML OT - chronic myeloid leukemia OT - deep molecular remission OT - imatinib OT - ropeginterferon alpha-2b EDAT- 2020/08/07 06:00 MHDA- 2021/01/12 06:00 CRDT- 2020/08/07 06:00 PHST- 2020/06/25 00:00 [received] PHST- 2020/07/27 00:00 [revised] PHST- 2020/08/02 00:00 [accepted] PHST- 2020/08/07 06:00 [pubmed] PHST- 2021/01/12 06:00 [medline] PHST- 2020/08/07 06:00 [entrez] AID - 10.1002/hon.2786 [doi] PST - ppublish SO - Hematol Oncol. 2020 Dec;38(5):792-798. doi: 10.1002/hon.2786. Epub 2020 Aug 19.