Dasatinib plus Peg-Interferon alpha 2b combination in newly diagnosed chronic phase chronic myeloid leukaemia: Results of a multicenter phase 2 study (DASA-PegIFN study)

被引：7

作者：

Roy, Lydia ^{[1
]}

Chomel, Jean-Claude ^{[2
]}

Guilhot, Joelle ^{[3
]}

Guerci-Bresler, Agnes ^{[4
]}

Escoffre-Barbe, Martine ^{[5
]}

Giraudier, Stephane ^{[6
,7
]}

Charbonnier, Aude ^{[8
]}

Dubruille, Viviane ^{[9
]}

Huguet, Francoise ^{[10
]}

Johnson-Ansah, Hyacinthe ^{[11
]}

Lenain, Pascal ^{[12
]}

Ame, Shanti ^{[13
]}

Etienne, Gabriel ^{[14
]}

Nicolini, Franck E. ^{[15
,16
]}

Rea, Delphine ^{[17
]}

Cony-Makhoul, Pascale ^{[18
]}

Courby, Stephane ^{[19
]}

Ianotto, Jean-Christophe ^{[20
]}

Legros, Laurence ^{[21
]}

Machet, Antoine ^{[22
]}

Coiteux, Valerie ^{[23
]}

Hermet, Eric ^{[24
]}

Cayssials, Emilie ^{[3
,25
]}

Bouchet, Stephane ^{[26
]}

Mahon, Francois-Xavier ^{[14
]}

Rousselot, Philippe ^{[27
]}

Guilhot, Francois ^{[3
]}

机构：

[1] Hop Univ Henri Mondor, AP HP, Serv Hematol Clin, UPEC,Fac Sante, Creteil, France

[2] CHU Poitiers, Serv Cancerol Biol, Poitiers, France

[3] CHU Poitiers, INSERM CIC 1402, Poitiers, France

[4] CHRU Brabois, Vandoeuvre les Nancy, Serv Hematol Clin, Nancy, France

[5] CHU Pontchaillou, Serv Hematol Clin, Rennes, France

[6] Hop St Louis, AP HP, Paris, France

[7] Univ Paris, INSERM, Serv Biol Cellulaire, Paris, France

[8] Inst Paoli Calmettes, Serv Hematol Clin, Marseille, France

[9] CHU Hotel Dieu, Serv Hematol Clin, Nantes, France

[10] CHU Toulouse, Serv Hematol Clin, IUCTO, Toulouse, France

[11] CHU Caen, Serv Hematol Clin, Caen, France

[12] Ctr Henri Becquerel, Serv Hematol Clin, Rouen, France

[13] CHU Strasbourg, Serv Hematol Clin, Strasbourg, France

[14] Inst Bergonie, Serv Hematol Clin, Bordeaux, France

[15] Ctr Leon Berard, Serv Hematol Clin, Lyon, France

[16] Ctr Leon Berard, INSERM U1052, CRC, Lyon, France

[17] Hop St Louis, AP HP, Serv Hematol Clin, Paris, France

[18] CH Annecy Genevois, Serv Hematol, Pringy, France

[19] CHU Grenoble, Serv Hematol Clin, Grenoble, France

[20] CHU Brest, Hop Morvan, Serv Hematol Clin, Brest, France

[21] Hop Paul Brousse, AP HP, Serv Hematol Clin, INSERM UMRS MD1197, Villejuif, France

[22] CHRU Tours, Hop Bretonneau, Serv Hematol Clin, Tours, France

[23] CHRU Lille, Hop Claude Huriez, Serv Hematol Clin, Lille, France

[24] CHU Estaing, Serv Hematol Clin, Clermont Ferrand, France

[25] CHU Poitiers, Serv Hematol Clin, Poitiers, France

[26] CHU Bordeaux, Hop Pellegrin, Lab Pharmacol, Bordeaux, France

[27] Univ Paris Saclay, Ctr Hosp Versailles, Serv Hematol Clin, UMR 1184, Le Chesnay, France

[28] Ctr Leon Berard, French CML Grp Fi LMC, Lyon, France

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2023年 / 200卷 / 02期

关键词：

chronic myeloid leukaemia; clinical trial; deep molecular response; pegylated-interferon; tyrosine kinase inhibitor; MOLECULAR RESPONSE; PEGINTERFERON ALPHA-2A; FOLLOW-UP; IMATINIB; NILOTINIB; REMISSION; EFFICACY; RATES;

D O I：

10.1111/bjh.18486

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Superior rates of deep molecular response (DMR) have been reported with the combination of tyrosine kinase inhibitors and pegylated-interferon-alpha (Peg-IFN) in patients with newly diagnosed chronic phase-chronic myeloid leukaemia (CP-CML). In this setting, this study investigated the efficacy and safety of dasatinib combined to Peg-IFN-alpha 2b (Dasa-PegIFN, NCT01872442). A total of 79 patients (age <= 65 years) started dasatinib; 61 were eligible for Peg-IFN alpha-2b add-on therapy at month 3 for a maximum 21-months duration. Dasatinib was continued thereafter. The primary endpoint was the cumulative rate of molecular response 4.5 log (MR4.5) by 12 months. The results are reported for the 5-year duration of the study. Grade 3 neutropenia was frequent with the combination but did not induce severe infection (one of grade 3). Other adverse events were generally low grade (4% of grade 3-4) and expected. Seventy-nine per cent and 61% of patients continued the Peg-IFN until months 12 and 24, respectively. Overall, at these time points, MR4.5 rates were 25% and 38%, respectively. Thereafter, 32% and 46% of patients achieved a sustained (>= 2 years) MR4.5 or MR4, respectively. This work established the feasibility and high rates of achievement of early and sustained DMR (a prerequisite for treatment-free-remission) with dasatinib and Peg-IFN alpha-2b combination as initial therapy.

引用

页码：175 / 186

页数：12

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