TY - JOUR
T1 - Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response
T2 - clinical and immunological effects
AU - Geelen, Inge G. P.
AU - Gullaksen, Stein-Erik
AU - Ilander, Mette M.
AU - Olssen-Strömberg, Ulla
AU - Mustjoki, Satu
AU - Richter, Johan
AU - Blijlevens, Nicole M. A.
AU - Smit, Willem M.
AU - Gjertsen, Bjorn T.
AU - Gedde-Dahl, Tobias
AU - Markevärn, Berit
AU - Koppes, Malika M. A.
AU - Westerweel, Peter E.
AU - Hjorth-Hansen, Henrik
AU - Janssen, Jeroen J. W. M.
N1 - Funding Information:
We thank the department of Applied Clinical Research (AKF) of the Norwegian University of Science and Technology (NTNU) for WebCRF and other assistance during this study. We thank the patients and all study personnel in the different centers for their efforts. The Amsterdam University medical centers, location VUmc, Amsterdam, The Netherlands, sponsored the study on behalf of the Nordic CML study Group (NCMLSG). The trial was supported by grants from Novartis Netherlands, Novartis Nordic countries, MSD Netherlands, MSD Sweden, MSD Norway and MSD Denmark to Amsterdam University medical centers, location VUmc. Neither sponsor, nor Novartis, nor MSD had any role in study design, collection, analysis or interpretation of data or preparation of this report. The mass cytometry substudy was supported by The Research Council of Norway (PETROMAKS program grant #220759), Helse Vest health trust (grant # F-12148) and the Norwegian Cancer Society with Solveig & Ole Lunds Legacy. The T cell receptor sequencing was performed at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki. Nordic Cancer Union supported the studies with NordicCML study group.
Funding Information:
We thank the department of Applied Clinical Research (AKF) of the Norwegian University of Science and Technology (NTNU) for WebCRF and other assistance during this study. We thank the patients and all study personnel in the different centers for their efforts. The Amsterdam University medical centers, location VUmc, Amsterdam, The Netherlands, sponsored the study on behalf of the Nordic CML study Group (NCMLSG). The trial was supported by grants from Novartis Netherlands, Novartis Nordic countries, MSD Netherlands, MSD Sweden, MSD Norway and MSD Denmark to Amsterdam University medical centers, location VUmc. Neither sponsor, nor Novartis, nor MSD had any role in study design, collection, analysis or interpretation of data or preparation of this report. The mass cytometry substudy was supported by The Research Council of Norway (PETROMAKS program grant #220759), Helse Vest health trust (grant # F-12148) and the Norwegian Cancer Society with Solveig & Ole Lunds Legacy. The T cell receptor sequencing was performed at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki. Nordic Cancer Union supported the studies with NordicCML study group.
Funding Information:
The Nordic CML Study group is an open academic forum for research on CML, and has performed clinical studies and received financing for this in collaboration with BMS, Novartis, Pfizer and MSD. Both Novartis and MSD supported the present study by provision of study drug free of charge and Novartis gave financial support for study administration. Individual investigators have the following ties to declare: JJWMJ received/receives research support from Novartis and BMS; honoraria for advisory boards from Pfizer and Incyte; speaker’s honoraria from Incyte and Pfizer. He is also the President of the Apps for Care and Science Foundation, that received funding for development of the HematologyApp from Abbvie, Alexion, Amgen, Astellas, Beigene, BMS, Daiichi-Sankyo, Eusapharma, Gilead, Incyte, Janssen pharmaceuticals, Jazz, Novartis, Pfizer, Takeda, Roche and Sanofi. SM has received research support and honoraria from BMS, Novartis and Pfizer.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1 IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1 IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile. This trial was registered at www.clinicaltrials.gov as #NCT01866553.
AB - In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1 IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1 IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile. This trial was registered at www.clinicaltrials.gov as #NCT01866553.
KW - Chronic myeloid leukemia
KW - Immunology
KW - Molecular response
KW - Nilotinib
KW - Pegylated interferon-alfa2b
KW - Quality of life
UR - https://www.scopus.com/pages/publications/85153971010
UR - https://www.ncbi.nlm.nih.gov/pubmed/37119314
UR - https://www.scopus.com/pages/publications/85153971010
U2 - 10.1007/s00277-023-05199-1
DO - 10.1007/s00277-023-05199-1
M3 - Article
C2 - 37119314
SN - 0939-5555
VL - 102
SP - 1395
EP - 1408
JO - Annals of hematology
JF - Annals of hematology
IS - 6
ER -
SDG 3 Good Health and Well-being