Modern Management Options for Ph+ ALL

Josep-Maria Ribera, Sabina Chiaretti, Josep-Maria Ribera, Sabina Chiaretti

Abstract

Impressive advances have been achieved in the management of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) since the initial concurrent use of imatinib and standard chemotherapy. The attenuation of chemotherapy has proven to be equally effective and less toxic, the use of third generation TKI upfront has improved the frequency of complete molecular response and the survival rate, and the combination of tyrosine kinase inhibitors with immunotherapy has further increased the rate of molecular response to 70-80% after consolidation, which has been translated into a survival rate of 75-90% in recent trials. As a result of these improvements, the role of allogeneic hematopoietic stem cell transplantation is being redefined. The methodology of measurable residual disease assessment and the detection of ABL1 mutations are also improving and will contribute to a more precise selection of the treatment for newly diagnosed and relapsed or refractory (R/R) patients. Finally, new compounds combined with immunotherapeutic approaches, including cellular therapy, are being used as rescue therapy and will hopefully be included in first line therapy in the near future. This article will review and update the modern management of patients with Ph+ ALL.

Keywords: Philadelphia chromosome; acute lymphoblastic leukemia; modern management.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed schema for allogeneic hematopoietic stem cell transplant (allo HSCT) for newly diagnosed patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). MRD: measurable residual disease; TKI: tyrosine kinase inhibitor.

References

    1. Foà R., Chiaretti S. Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2022;386:2399–2411. doi: 10.1056/NEJMra2113347.
    1. Chiaretti S., Vitale A., Cazzaniga G., Orlando S.M., Silvestri D., Fazi P., Valsecchi M.G., Elia L., Testi A.M., Mancini F., et al. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica. 2013;98:1702–1710. doi: 10.3324/haematol.2012.080432.
    1. Fielding A.K., Rowe J.M., Buck G., Foroni L., Gerrard G., Litzow M.R., Lazarus H., Luger S.M., Marks D.I., McMillan A.K., et al. UKALLXII/ECOG2993: Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014;123:843–850. doi: 10.1182/blood-2013-09-529008.
    1. Ribera J.-M., Oriol A., González M., Vidriales B., Brunet S., Esteve J., del Potro E., Rivas C., Moreno M.-J., Tormo M., et al. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica. 2009;95:87–95. doi: 10.3324/haematol.2009.011221.
    1. Daver N., Thomas D., Ravandi F., Cortes J., Garris R., Jabbour E., Garcia-Manero G., Borthakur G., Kadia T., Rytting M., et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100:653–661. doi: 10.3324/haematol.2014.118588.
    1. Chiaretti S., Vitale A., Vignetti M., Piciocchi A., Fazi P., Elia L., Falini B., Ronco F., Ferrara F., de Fabritiis P., et al. A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: Final results of the GIMEMA LAL 0904 study. Haematologica. 2016;101:1544–1552. doi: 10.3324/haematol.2016.144535.
    1. Chalandon Y., Thomas X., Hayette S., Cayuela J.M., Abbal C., Huguet F., Raffoux E., Leguay T., Rousselot P., Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) et al. Randomized study of reduced-intensity chemo-therapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015;125:3711–3719. doi: 10.1182/blood-2015-02-627935.
    1. Foà R., Vitale A., Vignetti M., Meloni G., Guarini A., De Propris M.S., Elia L., Paoloni F., Fazi P., Cimino G., et al. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood. 2011;118:6521–6528. doi: 10.1182/blood-2011-05-351403.
    1. Ravandi F., Othus M., O’Brien S.M., Forman S.J., Ha C.S., Wong J.Y.C., Tallman M.S., Paietta E., Racevskis J., Uy G.L., et al. US intergroup study of chemotherapy plus dasatinib and allogeneic stem cell transplant in Philadelphia chromosome positive ALL. Blood Adv. 2016;1:250–259. doi: 10.1182/bloodadvances.2016001495.
    1. Sugiura I., Doki N., Hata T., Cho R., Ito T., Suehiro Y., Tanaka M., Kako S., Matsuda M., Yokoyama H., et al. Dasatinib-based 2-step induction for adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood Adv. 2022;6:624–636. doi: 10.1182/bloodadvances.2021004607.
    1. Kim D.-Y., Joo Y.-D., Lim S.-N., Kim S.-D., Lee J.-H., Lee J.-H., Kim D.H., Kim K., Jung C.W., Kim I., et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015;126:746–756. doi: 10.1182/blood-2015-03-636548.
    1. Jain N., Maiti A., Ravandi F., Konopleva M., Daver N., Kadia T., Pemmaraju N., Short N., Kebriaei P., Ning J., et al. Inotuzumab ozogamicin with bosutinib for relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia or lymphoid blast phase of chronic myeloid leukemia. Am. J. Hematol. 2021;96:1000–1007. doi: 10.1002/ajh.26238.
    1. Vignetti M., Fazi P., Cimino G., Martinelli G., Di Raimondo F., Ferrara F., Meloni G., Ambrosetti A., Quarta G., Pagano L., et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without ad-ditional chemotherapy: Results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol. Blood. 2007;109:3676–3678.
    1. Rousselot P., Coudé M.M., Goekbuget N., Gambacorti Passerini C., Hayette S., Cayuela J.-M., Huguet F., Leguay T., Chevallier P., Salanoubat C., et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL. Blood. 2016;128:774–782. doi: 10.1182/blood-2016-02-700153.
    1. Short N.J., Jabbour E., Sasaki K., Patel K., O’Brien S.M., Cortes J.E., Garris R., Issa G.C., Garcia-Manero G., Luthra R., et al. Impact of complete molecular response on survival in patients with Philadelphia chromo-some-positive acute lymphoblastic leukemia. Blood. 2016;128:504–507. doi: 10.1182/blood-2016-03-707562.
    1. Sasaki K., Kantarjian H.M., Short N.J., Samra B., Khoury J.D., Kanagal Shamanna R., Konopleva M., Jain N., DiNardo C.D., Khouri R., et al. Prognostic factors for progression in patients with Philadelphia chromo-some-positive acute lymphoblastic leukemia in complete molecular response within 3 months of therapy with tyrosine kinase inhibitors. Cancer. 2021;127:2648–2656. doi: 10.1002/cncr.33529.
    1. Short N.J., Kantarjian H.M., Sasaki K., Ravandi F., Ko H., Cameron Yin C., Garcia-Manero G., Cortes J.E., Garris R., O’Brien S.M., et al. Poor outcomes associated with +der(22)t(9;22) and -9/9p in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor. Am. J. Hematol. 2017;92:238–243. doi: 10.1002/ajh.24625.
    1. Motlló C., Ribera J.-M., Morgades M., Granada I., Montesinos P., Mercadal S., González-Campos J., Moreno M.-J., Barba P., Cervera M., et al. Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia. Leuk. Lymphoma. 2017;59:146–154. doi: 10.1080/10428194.2017.1326596.
    1. Fedullo A.L., Messina M., Elia L., Piciocchi A., Gianfelici V., Lauretti A., Soddu S., Puzzolo M.C., Minotti C., Ferrara F., et al. Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2018;104:312–318. doi: 10.3324/haematol.2018.196055.
    1. Short N.J., Kantarjian H., Jabbour E. SOHO State of the Art Updates & Next Questions: Intensive and Non–Intensive Approaches for Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Clin. Lymphoma Myeloma Leuk. 2021;22:61–66. doi: 10.1016/j.clml.2021.08.003.
    1. Kim K., Jabbour E., Short N.J., Kebriaei P., Kantarjian H., Ravandi F. Current approaches to Philadelphia chromosome-positive B-cell Lineage Acute lymphoblastic leukemia: Role of tyrosine kinase inhibitor and tem cell transplant. Curr. Oncol Rep. 2021;23:95. doi: 10.1007/s11912-021-01086-y.
    1. Muffly L., Kebriaei P. Philadelphia chromosome positive acute lymphoblastic leukemia in adults: Therapeutic options and dilemmas in 2020. Semin. Hematol. 2020;57:137–141. doi: 10.1053/j.seminhematol.2020.09.002.
    1. Ansuinelli M., Cesini L., Chiaretti S., Foà R. Emerging tyrosine kinase inhibitors for the treatment of adult acute lymphoblastic leukemia. Expert Opin. Emerg. Drugs. 2021;26:281–294. doi: 10.1080/14728214.2021.1956462.
    1. Chiaretti S. Is Less More? Intensive versus non-intensive approach to adults with Ph+ ALL. Clin. Lymphoma Myeloma Leuk. 2020;20:S54–S55. doi: 10.1016/S2152-2650(20)30461-4.
    1. O’Hare T., Deininger M.W., Eide C.A., Clackson T., Druker B.J. Targeting the BCR-ABL Signaling Pathway in Therapy-Resistant Philadelphia Chromosome-Positive Leukemia. Clin. Cancer Res. 2011;17:212–221. doi: 10.1158/1078-0432.CCR-09-3314.
    1. Parker W.T., Yeung D.T.O., Yeoman A.L., Altamura H.K., Jamison B.A., Field C.R., Hodgson J.G., Lustgarten S., Rivera V.M., Hughes T., et al. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib. Blood. 2016;127:1870–1880. doi: 10.1182/blood-2015-09-666214.
    1. Cortes J.E., Kim D.-W., Pinilla-Ibarz J., Le Coutre P.D., Paquette R., Chuah C., Nicolini F.E., Apperley J.F., Khoury H.J., Talpaz M., et al. Ponatinib efficacy and safety in Philadelphia chromosome–positive leukemia: Final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393–404. doi: 10.1182/blood-2016-09-739086.
    1. Jabbour E., Kantarjian H., Ravandi F., Thomas D., Huang X., Faderl S., Pemmaraju N., Daver N., Garcia-Manero G., Sasaki K., et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromo-some-positive acute lymphoblastic leukaemia: A single-centre, phase 2 study. Lancet Oncol. 2015;16:1547–1555. doi: 10.1016/S1470-2045(15)00207-7.
    1. Jabbour E., Short N.J., Ravandi F., Huang X., Daver N., DiNardo C.D., Konopleva M., Pemmaraju N., Wierda W., Garcia-Manero G., et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: Long-term follow-up of a single-centre, phase 2 study. Lancet Haematol. 2018;5:e618–e627. doi: 10.1016/S2352-3026(18)30176-5.
    1. Sasaki K., Jabbour E.J., Ravandi F., Short N., Thomas D.A., Garcia-Manero G., Daver N.G., Kadia T.M., Konopleva M.Y., Jain N., et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A propensity score analysis. Cancer. 2016;122:3650–3656. doi: 10.1002/cncr.30231.
    1. Martinelli G., Papayannidis C., Piciocchi A., Robustelli V., Soverini S., Terragna C., Marconi G., Lemoli R.M., Guolo F., Fornaro A., et al. INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph+ acute lymphoblastic leukemia. Blood Adv. 2022;6:1742–1753. doi: 10.1182/bloodadvances.2021004821.
    1. Ribera J.-M., García-Calduch O., Ribera J., Montesinos P., Cano-Ferri I., Martínez P., Esteve J., Esteban D., García-Fortes M., Alonso N., et al. Ponatinib, Chemotherapy, and Transplant in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Blood Adv. 2022 doi: 10.1182/bloodadvances.2022007764.
    1. Martinelli G., Boissel N., Chevallier P., Ottmann O., Gökbuget N., Topp M.S., Fielding A.K., Rambaldi A., Ritchie E.K., Papayannidis C., et al. Complete Hematologic and Molecular Response in Adult Patients with Relapsed/Refractory Philadelphia Chromosome–Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J. Clin. Oncol. 2017;35:1795–1802. doi: 10.1200/JCO.2016.69.3531.
    1. Martinelli G., Boissel N., Chevallier P., Ottmann O., Gökbuget N., Rambaldi A., Ritchie E.K., Papayannidis C., Tuglus C.A., Morris J.D., et al. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome–positive B-cell precursor acute lymphoblastic leukaemia: Final analysis of ALCANTARA study. Eur. J. Cancer. 2021;146:107–114. doi: 10.1016/j.ejca.2020.12.022.
    1. Rambaldi A., Ribera J., Kantarjian H.M., Dombret H., Ottmann O.G., Stein A.S., Tuglus C.A., Zhao X., Kim C., Martinelli G. Blinatumomab compared with standard of care for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–positive B-precursor acute lymphoblastic leukemia. Cancer. 2019;126:304–310. doi: 10.1002/cncr.32558.
    1. Assi R., Kantarjian H., Short N.J., Daver N., Takahashi K., Garcia-Manero G., DiNardo C., Burger J., Cortes J., Jain N., et al. afety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome-positive Leukemia. Clin. Lymphoma Myeloma Leuk. 2017;17:897–901. doi: 10.1016/j.clml.2017.08.101.
    1. Stock W., Martinelli G., Stelljes M., Deangelo D.J., Gökbuget N., Advani A.S., O’Brien S., Liedtke M., Merchant A.A., Cassaday R.D., et al. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome–positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2020;127:905–913. doi: 10.1002/cncr.33321.
    1. Foà R., Bassan R., Vitale A., Elia L., Piciocchi A., Puzzolo M.-C., Canichella M., Viero P., Ferrara F., Lunghi M., et al. Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N. Engl. J. Med. 2020;383:1613–1623. doi: 10.1056/NEJMoa2016272.
    1. Chiaretti S., Bassan R., Vitale APiciocchi AFerrara F., Lunghi M., Fabbiano F., Bonifacio M., Nicola Fracchiolla N., Di Bartolomeo P., Fazi P., De Propris M.S., et al. Forty months update of the GIMEMA LAL2116 (D-ALBA) protocol and ancillary LAL2217 study for newly diagnosed adult Ph+ ALL. HemaSphere. 2022;6:253–254. doi: 10.1097/.
    1. Advani A., Moseley A., O’Dwyer K., Wood B., Park J.H., Wieduwilt M., Jeyakumar D., Yaghmour G., Atallah E.L., Gerds A.T., et al. A Phase 2 study of dasatinib, prednisone, and blina-tumomab for older patients with Philadelphia-chromosome (Ph) positive or Ph-like acute lymphoblastic leukemia (ALL) (with dasatinib sensitive fusions/ mutations) Blood. 2021;138:3397. doi: 10.1182/blood-2021-145529.
    1. Short N.J., Kantarjian H., Konopleva M., Jain N., Ravandi F., Huang X., Macaron W., Wierda W.G., Borthakur G., Kadia T., et al. Ponatinib and blinatumomab for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Updated results from a phase ii study. HemaSphere. 2022;6:15–16. doi: 10.1097/01.HS9.0000843352.55138.40.
    1. Lazaryan A., Dolan M., Zhang M.J., Wang H.L., Kharfan-Dabaja M.A., Marks D.I., Bejanyan N., Copelan E., Majhail N.S., Waller E.K., et al. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplan-tation: A study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Re-search. Haematologica. 2021;106:2295–2296.
    1. Pfeifer H., Raum K., Markovic S., Nowak V., Fey S., Obländer J., Pressler J., Böhm V., Brüggemann M., Wunderle L., et al. Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation. Blood. 2018;131:1464–1475. doi: 10.1182/blood-2017-07-796862.
    1. Chiaretti S., Ansuinelli M., Vitale A., Elia L., Matarazzo M., Piciocchi A., Fazi P., Di Raimondo F., Santoro L., Fabbiano F., et al. A multicenter total therapy strategy for de novo adult Philadelphia chromosome positive acute lymphoblastic leukemia patients: Final results of the GIMEMA LAL1509 protocol. Haematologica. 2021;106:1828–1838. doi: 10.3324/haematol.2020.260935.
    1. Sasaki M.Y., Kantarjian H.M., Short N.J., Jain N., Sasaki K., Ravandi M.F., Konopleva M., Garcia-Manero G., Little B.L., Gumbs C., et al. Prognostic Significance of Genetic Alterations in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated with Hyper-CVAD Plus Dasatinib or Hyper-CVAD Plus Ponatinib. Blood. 2020;136:40–41. doi: 10.1182/blood-2020-136676.
    1. Pfeifer H., Wassmann B., Bethge W., Dengler J., Bornhäuser M., Stadler M., Beelen D., Vucinic V., Burmeister T., Stelljes M., et al. Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR–ABL1-positive acute lymphoblastic leukemia. Leukemia. 2012;27:1254–1262. doi: 10.1038/leu.2012.352.
    1. Brissot E., Labopin M., Beckers M.M., Socié G., Rambaldi A., Volin L., Finke J., Lenhoff S., Kröger N., Ossenkoppele G.J., et al. Ty-rosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Haematologica. 2015;100:392–399. doi: 10.3324/haematol.2014.116954.
    1. Saini N.Y., Marin D., Ledesma C., Delgado R., Rondon G., Popat U.R., Bashir Q., Hosing C.M., Nieto Y., Alousi A.M., et al. Impact of TKIs post–allogeneic hematopoietic cell transplantation in Philadelphia chromosome–positive ALL. Blood. 2020;136:1786–1789. doi: 10.1182/blood.2019004685.
    1. Giebel S., Czyz A., Ottmann O., Baron F., Brissot E., Ciceri F., Cornelissen J.J., Esteve J., Gorin N.C., Savani B., et al. Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for pa-tients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer. 2016;122:2941–2951.
    1. Samra B., Kantarjian H.M., Sasaki K., Alotaibi A.S., Konopleva M., O’Brien S., Ferrajoli A., Garris R., Nunez C.A., Kadia T.M., et al. Discontinuation of Maintenance Tyrosine Kinase Inhibitors in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia outside of Transplant. Acta Haematol. 2020;144:285–292. doi: 10.1159/000510112.
    1. Park J.H., Rivière I., Gonen M., Wang X., Sénéchal B., Curran K.J., Sauter C., Wang Y., Santomasso B., Mead E., et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2018;378:449–459. doi: 10.1056/NEJMoa1709919.
    1. Shah B.D., Ghobadi A., Oluwole O.O., Logan A.C., Boissel N., Cassaday R.D., Leguay T., Bishop M.R., Topp M.S., Tzachanis D., et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: Phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet. 2021;398:491–502. doi: 10.1016/S0140-6736(21)01222-8.
    1. Couturier M.-A., Thomas X., Raffoux E., Huguet F., Berthon C., Simand C., Gallego-Hernanz M.-P., Hicheri Y., Berger M.H., Saillard C., et al. Blinatumomab + ponatinib for relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia in adults. Leuk. Lymphoma. 2020;62:620–629. doi: 10.1080/10428194.2020.1844198.
    1. Short N.J., Konopleva M., Kadia T., Kebriaei P., Daver N., Huang X., Masarova L., Cook R., Jain N., Jabbour E., et al. An effective chemotherapy-free regimen of ponatinib plus venetoclax for relapsed/refractory Philadelphia chro-mosome-positive acute lymphoblastic leukemia. Am. J. Hematol. 2021;96:E229–E232. doi: 10.1002/ajh.26175.
    1. Wang H., Yang C., Shi T., Zhang Y., Qian J., Wang Y., Hu Y., Mao L., Ye X., Liu F., et al. Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia. Blood Cancer J. 2022;12:20. doi: 10.1038/s41408-022-00621-9.
    1. Shen S., Chen X., Cai J., Yu J., Gao J., Hu S., Zhai X., Liang C., Ju X., Jiang H., et al. Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA Oncol. 2020;6:358–366. doi: 10.1001/jamaoncol.2019.5868.
    1. Hughes T.P., Mauro M.J., Cortes J.E., Minami H., Rea D., DeAngelo D.J., Breccia M., Goh Y.-T., Talpaz M., Hochhaus A., et al. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. New Engl. J. Med. 2019;381:2315–2326. doi: 10.1056/NEJMoa1902328.
    1. Eide C.A., Zabriskie M.S., Stevens S.L.S., Antelope O., Vellore N.A., Than H., Schultz A.R., Clair P., Bowler A.D., Pomicter A.D., et al. Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants. Cancer Cell. 2019;36:431–443.e5. doi: 10.1016/j.ccell.2019.08.004.
    1. Zerbit J., Tamburini J., Goldwirt L., Decroocq J., Cayuela J.M., Chapuis N., Contejean A., Batista R., Bouscary D., Willems L. Asciminib and ponatinib combination in Philadelphia chromosome-positive acute lymphoblastic leukemia. Leuk. Lymphoma. 2021;62:3558–3560. doi: 10.1080/10428194.2021.1966787.
    1. Leonard J.T., Rowley J.S.J., Eide C.A., Traer E., Hayes-Lattin B., Loriaux M., Spurgeon S.E., Druker B.J., Tyner J.W., Chang B.H. Targeting BCL-2 and ABL/LYN in Philadelphia chromosome–positive acute lymphoblastic leukemia. Sci. Transl. Med. 2016;8:354ra114. doi: 10.1126/scitranslmed.aaf5309.
    1. Bose P., Gandhi V., Konopleva M. Pathways and mechanisms of venetoclax resistance. Leuk. Lymphoma. 2017;58:2026–2039. doi: 10.1080/10428194.2017.1283032.

Source: PubMed

3
Subscribe