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. 2024 May;38(5):1072-1080.
doi: 10.1038/s41375-024-02204-y. Epub 2024 Mar 28.

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry

Annamaria Brioli  1   2   3 , Elza Lomaia  4 , Christian Fabisch  5 , Tomasz Sacha  6 , Hana Klamova  7 , Elena Morozova  8 , Aleksandra Golos  9 , Philipp Ernst  5 , Ulla Olsson-Stromberg  10 , Daniela Zackova  11 , Franck E Nicolini  12 , Han Bao  13 , Fausto Castagnetti  14   15 , Elzbieta Patkowska  16 , Jiri Mayer  11 , Klaus Hirschbühl  17 , Helena Podgornik  18   19 , Edyta Paczkowska  20 , Anne Parry  21 , Thomas Ernst  5 , Astghik Voskanyan  22 , Elzbieta Szczepanek  23 , Susanne Saussele  24 , Georg-Nikolaus Franke  25 , Alexander Kiani  26 , Edgar Faber  27 , Stefan Krause  28 , Luis Felipe Casado  29 , Krzysztof Lewandowski  30 , Matthias Eder  31 , Peter Anhut  32 , Justyna Gil  33 , Thomas Südhoff  34 , Holger Hebart  35 , Sonja Heibl  36 , Markus Pfirrmann  13 , Andreas Hochhaus  5 , Michael Lauseker  37
Affiliations

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry

Annamaria Brioli et al. Leukemia. 2024 May.

Abstract

Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015. Data reveal the expected heterogeneity of the entity, lacking a clear treatment standard. Outcomes remain dismal, with a median overall survival of 23.8 months (median follow up 27.8 months). Allogeneic stem cell transplantation (alloSCT) increases the rate of deep molecular responses. De novo BP and BP evolving from a previous CML do show slightly different features, suggesting a different biology between the two entities. Data show that outside clinical trials and in a real-world setting treatment of blast phase is individualized according to disease- and patient-related characteristics, with the aim of blast clearance prior to allogeneic stem cell transplantation. AlloSCT should be offered to all patients eligible for this procedure.

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Conflict of interest statement

The registry received no support from pharmacological companies. The single authors have the following conflict of interest do declare: AB has participated in advisory boards from BMS, Janssen, GSK, Takeda and Sanofi and received honoraria and travel support from BMS, Janssen, GSK, Sanofi, Amgen, Gilead and Takeda; EL has received fees for lecturing and expert opinion from Novartis, Pfizer, Sotex, Pharmstandard and Fusion Pharma; HK supported lectures from Novartis and Angelini, travel support form Novartis; EM has received honoraria and travel support from Novartis, BMS and Pfizer; AG has participated in advisory boards from Roche and received honoraria and travel support form AMGEN, Novartis, Janssen, Pfizer; PE has received research support from Novartis and participated on advisory boards for Pfizer; DZ served as a member of advisory board for Novartis, served on a speakers bureau for Novartis, Pfizer and Angelini, as a consultant for Novartis and Angelini, and received travel support from Novartis, Pfizer, Angelini and Astra Zeneca; EPat has received consulting fees from KCR US, Inc., received honoraria from Amgen, Novartis, Servier, Angelini Pharma, Astellas Pharma and Pfizer and travel support from Amgen, Novartis, Servier, Angelini Pharma, Astellas Pharma, Pfizer, Jazz Pharma and BMS; KH has participated in advisory boards from Pfizer, Novartis, Incyte and GSK and received honoraria and travel support from Jazz, Novartis, Gilead, Roche, Pfizer, Amgen, Astellas Pharma, Merck and AbbVie; TE has received research support from Novartis, BMS, Incyte, Pfizer; GNF has participated in advisory boards from Novartis, received honoraria from BMS, Novartis, Gilead, Pfizer, Jazz Pharma, received travel support from Stemline, Gilead, Takeda and research support from Novartis; AK has participated in advisory boards and received honoraria and travel support from BMS/Celgene, Novartis and Pfizer; EF has received honoraria from Angelini, Novartis and Zentiva, is member of the Czech Advisory board for Novartis and has participated in advisory boards from Zentiva; LFC has participated in advisory boards from Novartis, BMS, Janssen, GSK, Astra Zeneca, Incyte, Beigene and Pfizer and received honoraria and travel support from BMS, Janssen, GSK, Astra Zeneca and Pfizer; KL has received honoraria for lectures, chairing sessions from Novartis, AbbVie, Angelini, Celgene, Pfizer, AOP Orphan and participated in advisory boards from Novartis, AbbVie, Angelini, Celgene, Pfizer, AOP Orphan; HH has participated in advisory boards and/or received travel support from BMS, Incyte, Novartis, Pfizer; SH has participated in advisory boards of Novartis, Celgene, BMS, AOP Orphan, AbbVie, and has received honoraria from Novartis, Celgene, BMS, AOP Orphan, AbbVie, Sanofi, Amgen; AH has received research support from Novartis, BMS, Incyte, Pfizer, Enliven and TERNS; ML has received research support from Novartis. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Consort diagram of patients included in the registry and in the analysis.
BP blast phase, CP chronic phase.
Fig. 2
Fig. 2. Overall survival from diagnosis of blast phase (all population).
Median follow up 27.8 months.
Fig. 3
Fig. 3. Overall survival from diagnosis of blast phase according to different subgroups.
A overall survival for patient with central nervous system (CNS) and/or extramedullary (EM) involvement compared to patients without CNS and extramedullary involvement; B Overall survival for patient with de novo blast phase (CML-BP) and blast phase evolving from a previous chronic phase (CML-CP); C overall survival according to disease phenotype (myeloid vs. lymphoid); D overall survival according to disease phase (de novo) and ELTS score at the time of chronic phase (ELTS low, ELTS intermediate, ELTS high) [low ELTS vs. de novo HR 1.09 [95% CI: 0.68–1.75], p = 0.713, low ELTS vs. intermediate ELTS HR 2.35 [95% CI 1.35–4.11], p = 0.003, low ELTS vs. high ELTS HR 2.75 [95% CI: 1.57–4.81], p < 0.001]. All p values have to be interpreted as exploratory.
See this image and copyright information in PMC

References

    1. Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376:917–27. doi: 10.1056/NEJMoa1609324. - DOI - PMC - PubMed
    1. Hochhaus A, Burchert A, Saussele S, Baerlocher GM, Mayer J, Brümmendorf TH, et al. Treatment free remission after nilotinib plus peg-interferon alpha induction and peg-interferon alpha maintenance therapy for newly diagnosed chronic myeloid leukemia patients; the tiger trial. Blood. 2023;142:446. doi: 10.1182/blood-2023-182792. - DOI - PubMed
    1. Saussele S, Richter J, Guilhot J, Gruber FX, Hjorth-Hansen H, Almeida A, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19:747–57. doi: 10.1016/S1470-2045(18)30192-X. - DOI - PubMed
    1. Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gómez Casares MT, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31:1525–31. doi: 10.1038/leu.2017.63. - DOI - PMC - PubMed
    1. Mahon F-X, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11:1029–35. doi: 10.1016/S1470-2045(10)70233-3. - DOI - PubMed

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