Abstract
Original language | English |
---|---|
Pages (from-to) | 534-541 |
Number of pages | 8 |
Journal | Blood |
Volume | 135 |
Issue number | 8 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- BCR ABL protein
- BCR ABL1 protein
- protein tyrosine kinase inhibitor
- unclassified drug
- BCR-ABL1 fusion protein, human
- protein kinase inhibitor
- adult
- aged
- Article
- chronic myeloid leukemia
- clinical decision making
- feasibility study
- gene mutation
- genetic screening
- health care cost
- high throughput sequencing
- human
- major clinical study
- mutational analysis
- priority journal
- prospective study
- Sanger sequencing
- treatment response
- turnaround time
- clinical trial
- drug resistance
- female
- genetics
- male
- middle aged
- multicenter study
- mutation
- mutation rate
- very elderly
- Adult
- Aged
- Aged, 80 and over
- Drug Resistance, Neoplasm
- Female
- Fusion Proteins, bcr-abl
- High-Throughput Nucleotide Sequencing
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Male
- Middle Aged
- Mutation
- Mutation Rate
- Prospective Studies
- Protein Kinase Inhibitors
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Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study. / Soverini, S.; Bavaro, L.; de Benedittis, C.; Martelli, M.; Iurlo, A.; Orofino, N.; Sica, S.; Sorà, F.; Lunghi, F.; Ciceri, F.; Galimberti, S.; Baratè, C.; Bonifacio, M.; Scaffidi, L.; Castagnetti, F.; Gugliotta, G.; Albano, F.; Rossi, A.V.R.; Stagno, F.; di Raimondo, F.; D'Adda, M.; di Bona, E.; Abruzzese, E.; Binotto, G.; Sancetta, R.; Salvucci, M.; Capodanno, I.; Girasoli, M.; Coluzzi, S.; Attolico, I.; Musolino, C.; Calistri, E.; Annunziata, M.; Bocchia, M.; Stella, S.; Serra, A.; Errichiello, S.; Saglio, G.; Pane, F.; Vigneri, P.; Mignone, F.; Laginestra, M.A.; Pileri, S.A.; Percesepe, A.; Tenti, E.; Rosti, G.; Baccarani, M.; Cavo, M.; Martinelli, G.
In: Blood, Vol. 135, No. 8, 2020, p. 534-541.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: The NEXT-in-CML study
AU - Soverini, S.
AU - Bavaro, L.
AU - de Benedittis, C.
AU - Martelli, M.
AU - Iurlo, A.
AU - Orofino, N.
AU - Sica, S.
AU - Sorà, F.
AU - Lunghi, F.
AU - Ciceri, F.
AU - Galimberti, S.
AU - Baratè, C.
AU - Bonifacio, M.
AU - Scaffidi, L.
AU - Castagnetti, F.
AU - Gugliotta, G.
AU - Albano, F.
AU - Rossi, A.V.R.
AU - Stagno, F.
AU - di Raimondo, F.
AU - D'Adda, M.
AU - di Bona, E.
AU - Abruzzese, E.
AU - Binotto, G.
AU - Sancetta, R.
AU - Salvucci, M.
AU - Capodanno, I.
AU - Girasoli, M.
AU - Coluzzi, S.
AU - Attolico, I.
AU - Musolino, C.
AU - Calistri, E.
AU - Annunziata, M.
AU - Bocchia, M.
AU - Stella, S.
AU - Serra, A.
AU - Errichiello, S.
AU - Saglio, G.
AU - Pane, F.
AU - Vigneri, P.
AU - Mignone, F.
AU - Laginestra, M.A.
AU - Pileri, S.A.
AU - Percesepe, A.
AU - Tenti, E.
AU - Rosti, G.
AU - Baccarani, M.
AU - Cavo, M.
AU - Martinelli, G.
N1 - Cited By :15 Export Date: 5 March 2021 CODEN: BLOOA Correspondence Address: Soverini, S.; Institute of Hematology “L. e A. Seràgnoli,”, Via Massarenti 9, Italy; email: simona.soverini@unibo.it Chemicals/CAS: BCR-ABL1 fusion protein, human; Fusion Proteins, bcr-abl; Protein Kinase Inhibitors Funding details: Novartis Funding details: Teva Pharmaceutical Industries Funding details: Bristol-Myers Squibb, BMS Funding details: Pfizer Funding details: Celgene Funding text 1: Conflict-of-interest disclosure: S. Soverini received honoraria from Incyte Biosciences, Novartis, and Bristol-Myers Squibb; M. Baccarani received honoraria from Novartis, Incyte Biosciences, and Pfizer; S.G. received speaker fees from Pfizer, Novartis, and Incyte Biosciences; A.I. received honoraria from Novartis, Pfizer, and Incyte Biosciences; G.R., F. Castagnetti, G.G., F.S., and E.A. received honoraria from Novartis, Bristol-Myers Squibb, Pfizer, and Incyte Biosciences; P.V. received honoraria from Astra Zeneca, Celgene, Incyte Biosciences, Italfarmaco, Novartis, Pfizer, Tesaro, and Teva and research funding from Novartis and Pfizer. The remaining authors declare no competing financial interests. References: Cortes, J., Kantarjian, H., How I treat newly diagnosed chronic phase CML (2012) Blood, 120 (7), pp. 1390-1397; Soverini, S., Mancini, M., Bavaro, L., Cavo, M., Martinelli, G., Chronic myeloid leukemia: The paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy (2018) Mol Cancer, 17 (1), p. 49; Jabbour, E., Kantarjian, H., Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring (2018) Am J Hematol, 93 (3), pp. 442-459; Soverini, S., Martinelli, G., Rosti, G., Iacobucci, I., Baccarani, M., Advances in treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: The evolving role of Bcr-Abl mutations and mutational analysis (2012) Pharmacogenomics, 13 (11), pp. 1271-1284; Soverini, S., de Benedittis, C., Mancini, M., Martinelli, G., Best practices in chronic myeloid leukemia monitoring and management (2016) Oncologist, 21 (5), pp. 626-633; Soverini, S., Gnani, A., Colarossi, S., Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- Or third-line tyrosine kinase inhibitors (2009) Blood, 114 (10), pp. 2168-2171; Hughes, T., Saglio, G., Branford, S., Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase (2009) J Clin Oncol, 27 (25), pp. 4204-4210; Müller, M.C., Cortes, J.E., Kim, D.W., Dasatinib treatment of chronic-phase chronic myeloid leukemia: Analysis of responses according to preexisting BCR-ABL mutations (2009) Blood, 114 (24), pp. 4944-4953; Zabriskie, M.S., Eide, C.A., Tantravahi, S.K., BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia (2014) Cancer Cell, 26 (3), pp. 428-442; Soverini, S., Hochhaus, A., Nicolini, F.E., BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: Recommendations from an expert panel on behalf of European LeukemiaNet (2011) Blood, 118 (5), pp. 1208-1215; NCCN Clinical Practice Guidelines in Oncology: Chronic Myeloid Leukemia, , https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf, Version 2. 2020. Accessed 20 October, 2019; Kohlmann, A., Klein, H.U., Weissmann, S., The Interlaboratory RObustness of Next-generation sequencing (IRON) study: A deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories (2011) Leukemia, 25 (12), pp. 1840-1848; Soverini, S., de Benedittis, C., Polakova, K.M., Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients (2016) Oncotarget, 7 (16), pp. 21982-21990; Soverini, S., de Benedittis, C., Machova Polakova, K., Unraveling the complexity of tyrosine kinase inhibitor-resistant populations by ultra-deep sequencing of the BCR-ABL kinase domain (2013) Blood, 122 (9), pp. 1634-1648; Soverini, S., de Benedittis, C., Papayannidis, C., Clinical impact of low-burden BCR-ABL1 mutations detectable by amplicon deep sequencing in Philadelphia-positive acute lymphoblastic leukemia patients (2016) Leukemia, 30 (7), pp. 1615-1619; Baer, C., Kern, W., Koch, S., Ultra-deep sequencing leads to earlier and more sensitive detection of the tyrosine kinase inhibitor resistance mutation T315I in chronic myeloid leukemia (2016) Haematologica, 101 (7), pp. 830-838; Machova Polakova, K., Kulvait, V., Benesova, A., Next-generation deep sequencing improves detection of BCR-ABL1 kinase domain mutations emerging under tyrosine kinase inhibitor treatment of chronic myeloid leukemia patients in chronic phase (2015) J Cancer Res Clin Oncol, 141 (5), pp. 887-899; Szankasi, P., Schumacher, J.A., Kelley, T.W., Detection of BCR-ABL1 mutations that confer tyrosine kinase inhibitor resistance using massively parallel, next generation sequencing (2016) Ann Hematol, 95 (2), pp. 201-210; Kizilors, A., Crisa, E., Lea, N., Effect of low level mutations identified by next-generation sequencing in patients with chronic myeloid leukaemia: A population-based study (2019) Lancet Haematol, 6 (5), pp. e276-e284; Kastner, R., Zopf, A., Preuner, S., Rapid identification of compound mutations in patients with Philadelphia-positive leukaemias by long-range next generation sequencing (2014) Eur J Cancer, 50 (4), pp. 793-800; Soverini, S., Martinelli, G., Amabile, M., Denaturing-HPLC-based assay for detection of ABL mutations in chronic myeloid leukemia patients resistant to Imatinib (2004) Clin Chem, 50 (7), pp. 1205-1213; Kohlmann, A., Martinelli, G., Hofmann, W.-K., The interlaboratory robustness of next-generation sequencing (IRON) study phase II: Deep-sequencing analyses of hematological malignancies performed by an international network involving 26 laboratories (2012) Blood, 120 (21), p. 1399; Parker, W.T., Ho, M., Scott, H.S., Hughes, T.P., Branford, S., Poor response to second-line kinase inhibitors in chronic myeloid leukemia patients with multiple low-level mutations, irrespective of their resistance profile (2012) Blood, 119 (10), pp. 2234-2238; Schmitt, M.W., Pritchard, J.R., Leighow, S.M., Single-molecule sequencing reveals patterns of preexisting drug resistance that suggest treatment strategies in philadelphia-positive leukemias (2018) Clin Cancer Res, 24 (21), pp. 5321-5334; Parker, W.T., Lawrence, R.M., Ho, M., Sensitive detection of BCR-ABL1 mutations in patients with chronic myeloid leukemia after imatinib resistance is predictive of outcome during subsequent therapy (2011) J Clin Oncol, 29 (32), pp. 4250-4259; Parker, W.T., Yeoman, A.L., Jamison, B.A., BCR-ABL1 kinase domain mutations may persist at very low levels for many years and lead to subsequent TKI resistance (2013) Br J Cancer, 109 (6), pp. 1593-1598; Parker, W.T., Yeung, D.T., Yeoman, A.L., The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib (2016) Blood, 127 (15), pp. 1870-1880
PY - 2020
Y1 - 2020
N2 - In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n 5 124) or warning (n 5 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms. © 2020 American Society of Hematology. All rights reserved.
AB - In chronic myeloid leukemia (CML) patients, tyrosine kinase inhibitors (TKIs) may select for drug-resistant BCR-ABL1 kinase domain (KD) mutants. Although Sanger sequencing (SS) is considered the gold standard for BCR-ABL1 KD mutation screening, next-generation sequencing (NGS) has recently been assessed in retrospective studies. We conducted a prospective, multicenter study (NEXT-in-CML) to assess the frequency and clinical relevance of low-level mutations and the feasibility, cost, and turnaround times of NGS-based BCR-ABL1 mutation screening in a routine setting. A series of 236 consecutive CML patients with failure (n 5 124) or warning (n 5 112) response to TKI therapy were analyzed in parallel by SS and NGS in 1 of 4 reference laboratories. Fifty-one patients (22 failure, 29 warning) who were negative for mutations by SS had low-level mutations detectable by NGS. Moreover, 29 (27 failure, 2 warning) of 60 patients who were positive for mutations by SS showed additional low-level mutations. Thus, mutations undetectable by SS were identified in 80 out of 236 patients (34%), of whom 42 (18% of the total) had low-level mutations somehow relevant for clinical decision making. Prospective monitoring of mutation kinetics demonstrated that TKI-resistant low-level mutations are invariably selected if the patients are not switched to another TKI or if they are switched to a inappropriate TKI or TKI dose. The NEXT-in-CML study provides for the first time robust demonstration of the clinical relevance of low-level mutations, supporting the incorporation of NGS-based BCR-ABL1 KD mutation screening results in the clinical decision algorithms. © 2020 American Society of Hematology. All rights reserved.
KW - BCR ABL protein
KW - BCR ABL1 protein
KW - protein tyrosine kinase inhibitor
KW - unclassified drug
KW - BCR-ABL1 fusion protein, human
KW - protein kinase inhibitor
KW - adult
KW - aged
KW - Article
KW - chronic myeloid leukemia
KW - clinical decision making
KW - feasibility study
KW - gene mutation
KW - genetic screening
KW - health care cost
KW - high throughput sequencing
KW - human
KW - major clinical study
KW - mutational analysis
KW - priority journal
KW - prospective study
KW - Sanger sequencing
KW - treatment response
KW - turnaround time
KW - clinical trial
KW - drug resistance
KW - female
KW - genetics
KW - male
KW - middle aged
KW - multicenter study
KW - mutation
KW - mutation rate
KW - very elderly
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Drug Resistance, Neoplasm
KW - Female
KW - Fusion Proteins, bcr-abl
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive
KW - Male
KW - Middle Aged
KW - Mutation
KW - Mutation Rate
KW - Prospective Studies
KW - Protein Kinase Inhibitors
U2 - 10.1182/blood.2019002969
DO - 10.1182/blood.2019002969
M3 - Article
VL - 135
SP - 534
EP - 541
JO - Blood
JF - Blood
SN - 0006-4971
IS - 8
ER -