Impact of minimal residual disease response and of status of disease on survival after blinatumomab in B-cell acute lymphoblastic leukemia: results from a real-life study.

Acute lymphoblastic leukaemia Blinatumomab Minimal residual disease Real-life

Journal

Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334

Informations de publication

Date de publication:
13 Apr 2024
Historique:
received: 25 02 2024
accepted: 21 03 2024
medline: 13 4 2024
pubmed: 13 4 2024
entrez: 12 4 2024
Statut: aheadofprint

Résumé

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment.

Identifiants

pubmed: 38609726
doi: 10.1007/s00277-024-05725-9
pii: 10.1007/s00277-024-05725-9
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Références

DeAngelo DJ, Jabbour E, Advani A (2020) Recent Advances in Managing Acute Lymphoblastic Leukemia. Am Soc Clin Oncol Educ Book. ;40:330–342. https://doi.org/10.1200/EDBK_280175 . PMID: 32421447
Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C, ESMO Guidelines Committee (2016) Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 27(5):v69–v82. https://doi.org/10.1093/annonc/mdw025 Epub 2016 Apr 7. PMID: 27056999
doi: 10.1093/annonc/mdw025 pubmed: 27056999
Malard F, Mohty M (2020) Acute lymphoblastic leukaemia. Lancet. ;395(10230):1146–1162. https://doi.org/10.1016/S0140-6736(19)33018-1 . PMID: 32247396
Brüggemann M, Kotrova M (2017) Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Blood Adv 1(25):2456–2466. https://doi.org/10.1182/bloodadvances.2017009845 PMID: 29296895; PMCID: PMC5729622
doi: 10.1182/bloodadvances.2017009845 pubmed: 29296895 pmcid: 5729622
Lussana F, Intermesoli T, Gianni F, Boschini C, Masciulli A, Spinelli O, Oldani E, Tosi M, Grassi A, Parolini M, Audisio E, Cattaneo C, Raimondi R, Angelucci E, Cavattoni IM, Scattolin AM, Cortelezzi A, Mannelli F, Ciceri F, Mattei D, Borlenghi E, Terruzzi E, Romani C, Bassan R, Rambaldi A (2016) Achieving Molecular Remission before Allogeneic Stem Cell transplantation in adult patients with Philadelphia chromosome-positive Acute Lymphoblastic Leukemia: impact on Relapse and Long-Term Outcome. Biol Blood Marrow Transpl 22(11):1983–1987. https://doi.org/10.1016/j.bbmt.2016.07.021 Epub 2016 Aug 1. PMID: 27492792
doi: 10.1016/j.bbmt.2016.07.021
Candoni A, Rambaldi A, Fanin R, Velardi A, Arcese W, Ciceri F, Lazzarotto D, Lussana F, Olivieri J, Grillo G, Parma M, Bruno B, Sora F, Bernasconi P, Saccardi R, Foà R, Sessa M, Bresciani P, Giglio F, Picardi A, Busca A, Sica S, Perruccio K, Zucchetti E, Diral E, Iori AP, Colombo AA, Tringali S, Santarone S, Irrera G, Mancini S, Zallio F, Malagola M, Albano F, Carella AM, Olivieri A, Tecchio C, Dominietto A, Vacca A, Sorasio R, Orciuolo E, Risitano AM, Leotta S, Cortelezzi A, Mammoliti S, Oldani E, Bonifazi F (2019) GITMO. Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome-positive Acute Lymphoblastic Leukemia in the era of tyrosine kinase inhibitors: a Registry-based study of the Italian blood and marrow transplantation society (GITMO). Biol Blood Marrow Transpl 25(12):2388–2397. https://doi.org/10.1016/j.bbmt.2019.07.037 Epub 2019 Aug 7. PMID: 31400502
doi: 10.1016/j.bbmt.2019.07.037
Portell CA, Wenzell CM, Advani AS (2013) Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol 5(Suppl 1):5–11. https://doi.org/10.2147/CPAA.S42689 PMID: 23671399; PMCID: PMC3650887
doi: 10.2147/CPAA.S42689 pubmed: 23671399 pmcid: 3650887
Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foà R, Bassan R, Arslan Ö, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Brüggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS (2017) Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med 376(9):836–847. https://doi.org/10.1056/NEJMoa1609783 PMID: 28249141; PMCID: PMC5881572
doi: 10.1056/NEJMoa1609783 pubmed: 28249141 pmcid: 5881572
Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Brüggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC (2018) Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. ;131(14):1522–1531. https://doi.org/10.1182/blood-2017-08-798322 . Epub 2018 Jan 22. Erratum in: Blood. 2019;133(24):2625. PMID: 29358182; PMCID: PMC6027091
National Cancer Institute Common terminology criteria for adverse events (CTCAE). Version 5.0. Available at: https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf
Lee DW, Gardner R, Porter DL et al (2014) Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124:188–195
doi: 10.1182/blood-2014-05-552729 pubmed: 24876563 pmcid: 4093680
Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van’t Veer MB (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9(10):1783–1786 PMID: 7564526
pubmed: 7564526
Winick N, Devidas M, Chen S, Maloney K, Larsen E, Mattano L, Borowitz MJ, Carroll A, Gastier-Foster JM, Heerema NA, Willman C, Wood B, Loh ML, Raetz E, Hunger SP, Carroll WL, Impact of Initial CSF Findings on Outcome Among Patients With National Cancer Institute Standard- (2017) And high-risk B-Cell Acute Lymphoblastic Leukemia: a Report from the children’s Oncology Group. J Clin Oncol 35(22):2527–2534 Epub 2017 May 23. PMID: 28535084; PMCID: PMC5536164
doi: 10.1200/JCO.2016.71.4774 pubmed: 28535084 pmcid: 5536164
Bassan R, Brüggemann M, Radcliffe HS, Hartfield E, Kreuzbauer G, Wetten S (2019) A systematic literature review and meta-analysis of minimal residual disease as a prognostic indicator in adult B-cell acute lymphoblastic leukemia. Haematologica 104(10):2028–2039. https://doi.org/10.3324/haematol.2018.201053 Epub 2019 Mar 19. PMID: 30890593; PMCID: PMC6886415
doi: 10.3324/haematol.2018.201053 pubmed: 30890593 pmcid: 6886415
Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, Wood BL, Kelloff GJ, Jessup JM, Radich JP (2017) Association of minimal residual Disease with Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: a Meta-analysis. JAMA Oncol 3(7):e170580. https://doi.org/10.1001/jamaoncol.2017.0580 Epub 2017 Jul 13. PMID: 28494052; PMCID: PMC5824235
doi: 10.1001/jamaoncol.2017.0580 pubmed: 28494052 pmcid: 5824235
Gökbuget N, Zugmaier G, Dombret H, Stein A, Bonifacio M, Graux C, Faul C, Brüggemann M, Taylor K, Mergen N, Reichle A, Horst HA, Havelange V, Topp MS, Bargou RC (2020) Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. ;61(11):2665–2673. doi: 10.1080/10428194.2020.1780583. Epub 2020 Jul 3. PMID: 32619115
Cabannes-Hamy A, Brissot E, Leguay T, Huguet F, Chevallier P, Hunault M, Escoffre-Barbe M, Cluzeau T, Balsat M, Nguyen S, Pasquier F, Alexis M, Lheritier V, Pastoret C, Delabesse E, Clappier E, Dombret H, Boissel N (2022) High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL. Haematologica 107(9):2072–2080. https://doi.org/10.3324/haematol.2021.280078 PMID: 35263986; PMCID: PMC9425331
doi: 10.3324/haematol.2021.280078 pubmed: 35263986 pmcid: 9425331
Queudeville M, Stein AS, Locatelli F, Ebinger M, Handgretinger R, Gökbuget N, Gore L, Zeng Y, Gokani P, Zugmaier G, Kantarjian HM (2023) Low leukemia burden improves blinatumomab efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Cancer 129(9):1384–1393. https://doi.org/10.1002/cncr.34667 Epub 2023 Feb 24. PMID: 36829303
doi: 10.1002/cncr.34667 pubmed: 36829303
Topp MS, Stein AS, Gökbuget N, Horst HA, Boissel N, Martinelli G, Kantarjian H, Brüggemann M, Chen Y, Zugmaier G (2021) Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: results of a pooled analysis. Cancer Med 10(8):2601–2610 Epub 2021 Mar 18. PMID: 33734596; PMCID: PMC8026950
doi: 10.1002/cam4.3731 pubmed: 33734596 pmcid: 8026950
Badar T, Szabo A, Advani A, Wadleigh M, Arslan S, Khan MA, Aldoss I, Siebenaller C, Schultz E, Hefazi M, Shallis RM, Yurkiewicz I, Podoltsev N, Patel AA, Curran E, Balasubramanian S, Yang J, Mattison RJ, Burkart M, Dinner S, Liedtke M, Litzow MR, Atallah E (2020) Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab. Blood Adv 4(10):2308–2316. https://doi.org/10.1182/bloodadvances.2019001381 PMID: 32453836; PMCID: PMC7252553
doi: 10.1182/bloodadvances.2019001381 pubmed: 32453836 pmcid: 7252553
Boissel N, Chiaretti S, Papayannidis C, Ribera JM, Bassan R, Sokolov AN, Alam N, Brescianini A, Pezzani I, Kreuzbauer G, Zugmaier G, Foà R, Rambaldi A (2023) Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice: results from the NEUF study. Blood Cancer J 13(1):2. https://doi.org/10.1038/s41408-022-00766-7 PMID: 36599847; PMCID: PMC9813344
doi: 10.1038/s41408-022-00766-7 pubmed: 36599847 pmcid: 9813344
Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bourquin JP, Handgretinger R, Brethon B, Rossig C, Chen-Santel C (2020) Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study. Blood Cancer J. ;10(7):77. doi: 10.1038/s41408-020-00342-x. Erratum in: Blood Cancer J. 2021;11(2):28. Erratum in: Blood Cancer J. 2021;11(10):173. PMID: 32709851; PMCID: PMC7381625
Keating AK, Gossai N, Phillips CL, Maloney K, Campbell K, Doan A, Bhojwani D, Burke MJ, Verneris MR (2019) Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Adv 3(13):1926–1929. https://doi.org/10.1182/bloodadvances.2018025726 PMID: 31243002; PMCID: PMC6616259
doi: 10.1182/bloodadvances.2018025726 pubmed: 31243002 pmcid: 6616259
Apel A, Ofran Y, Wolach O, Shimony S, Ram R, Levi I, Zektser M, Koren-Michowitz M (2020) Safety and efficacy of blinatumomab: a real world data. Ann Hematol 99(4):835–838. https://doi.org/10.1007/s00277-019-03854-0 Epub 2020 Feb 20. PMID: 32076826
doi: 10.1007/s00277-019-03854-0 pubmed: 32076826
Chauvet P, Paviglianiti A, Labopin M, Labussière H, Boissel N, Robin M, Maillard N, Ouachée-Chardin M, Forcade E, Poiré X, Chantepie S, Huynh A, Bulabois CE, Leclerc M, Maury S, Chevallier P, Cluzeau T, Mear JB, Cornillon J, Bilger K, Simand C, Beguin Y, Rubio MT, Yakoub-Agha I, Brissot E (2023) Combining blinatumomab and donor lymphocyte infusion in B-ALL patients relapsing after allogeneic hematopoietic cell transplantation: a study of the SFGM-TC. Bone Marrow Transpl 58(1):72–79. https://doi.org/10.1038/s41409-022-01846-9 Epub 2022 Oct 19. PMID: 36261707
doi: 10.1038/s41409-022-01846-9

Auteurs

Salvatore Leotta (S)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy. leotta3@yahoo.it.
Divisione di Ematologia - Azienda Ospedaliero, Universitaria Policlinico "G. Rodolico - San Marco", Via Santa Sofia, 78, Catania, 95123, Italy. leotta3@yahoo.it.

Uros Markovic (U)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Andrea Duminuco (A)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Antonino Mulè (A)

Oncohematology Unit - AO Villa Sofia - Cervello, Palermo, Italy.

Ferdinando Porretto (F)

Hematology Unit, Ospedale "La Maddalena", Palermo, Italy.

Vincenzo Federico (V)

Haematology and Stem Cell Transplant Unit, Presidio Ospedaliero "Vito Fazzi", Lecce, Italy.

Massimo Gentile (M)

Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Department of Pharmacy, Health and Nutritional Science, University of Calabria, Rende, Italy.

Domenico Pastore (D)

Hematology, A. Perrino Hospital, Brindisi, Italy.

Luca Lo Nigro (LL)

Pediatric Hematology-Oncology, Azienda Policlinico "G. Rodolico-San Marco", Catania, Italy.

Carmine Selleri (C)

Oncohematology Department and Transplant Center, University of Salerno - AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.

Bianca Serio (B)

Oncohematology Department and Transplant Center, University of Salerno - AOU San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.

Valeria Calafiore (V)

Oncohematology Unit - AO Villa Sofia - Cervello, Palermo, Italy.

Caterina Patti (C)

Oncohematology Unit - AO Villa Sofia - Cervello, Palermo, Italy.

Elisa Mauro (E)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Calogero Vetro (C)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Cinzia Maugeri (C)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Marina Parisi (M)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Paolo Fiumara (P)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Laura Parrinello (L)

Cytometryc Lab, Division of Haematology, A.O.U. Policlinico "G.Rodolico - S. Marco", Catania, Italy.

Sara Marino (S)

Cytometryc Lab, Division of Haematology, A.O.U. Policlinico "G.Rodolico - S. Marco", Catania, Italy.

Grazia Scuderi (G)

Cytometryc Lab, Division of Haematology, A.O.U. Policlinico "G.Rodolico - S. Marco", Catania, Italy.

Bruno Garibaldi (B)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Maurizio Musso (M)

Hematology Unit, Ospedale "La Maddalena", Palermo, Italy.

Nicola Di Renzo (ND)

Haematology and Stem Cell Transplant Unit, Presidio Ospedaliero "Vito Fazzi", Lecce, Italy.

Ernesto Vigna (E)

Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.

Enrica Antonia Martino (EA)

Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.

Francesco Di Raimondo (FD)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Giuseppe Milone (G)

Hematology and BMT Unit, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico-San Marco", Catania, Italy.

Classifications MeSH