BLINATUMOMAB IN THE THERAPY OF ACUTE B-LYMPHOID LEUKEMIA BLINATUMOMAB and ALL

Main Article Content

Ugo Testa
Elvira Pelosi
Germana Castelli
Patrizia Chiusolo

Keywords

Blinatumomab, ALL, Immunotherapy; bispecific antibody

Abstract

Blinatumomab, a CD19-CD3 bispecific T cell engager (BiTE), has two recombinant single-chain variable fragments that temporarily link CD3+ T cells and CD19+ B cells, leading to the T cell-mediated lysis of neoplastic B cells. Improved minimal residual disease (MRD)-negative response rates and long-term overall survival have been observed in B-ALL patients who received this drug. These therapeutic successes have led to FDA approval for refractory/relapsed and MRD-positive B-ALL patients. Furthermore, recent studies in newly diagnosed B-ALL patients have led in Philadelphia chromosome-positive patients to the development of chemotherapy-free regimens based on tyrosine kinase inhibitors plus Blinatumomab and in Philadelphia chromosome-negative patients to improvement in outcomes using chemotherapy regimens that have incorporated Blinatumomab in the consolidation phase of treatment.

Downloads

Download data is not yet available.


Abstract 0
PDF Downloads 0

References

1) Klein C, Brinkmann U, Reichert JM, Kontermann RE. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov 2024
2) Surowka M, Klein C. A pivotal decade for bispecific antibodies? MABS 2024; 16: 2321625.
3) Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, Einsele M, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008; 321: 974-977.
4) Kantarjian H, Stein A; Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A; Dombret H, Foa R, Bassan R, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017; 3: 836-847.
5) Topp MS, Gokbuget N, Zugmaier G, Stein AS, Dombret H, Chen Y, Ribera JM,Bargou RF, Horst HA, Kantarjian H. Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with Blinatumomab. Cancer 2021; 127: 554-559.
6) ToppMS, Stein AS, Gokbuget N, Horst HA, Boissel N, Martinelli G, Kantarjian H, Bruggemann M, Chen Y, Zugmaier G. 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 2021; 1: 2601-2610.
7) Boissel N, Chiaretti S, Papayannidis C, Ribera JM, Bassan R, Sokolov AN, Alam N, Brescianini A, Pezzani I, Kreuzbauer G, et al. 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 2023; 13:2.
8) Webster JA, Luskin MR, Rimando J, Blackford A, Zeidan AM, Sharon E, Stericher H, DeAngelo DJ, Uznik L, Gojo I, et al. Blinatumomab in combination with immune checkpoint inhibitors (ICIs) of PD-1 and CTLA-4 in adult patients with relapsed/refractory (R/R) CD19 positive B-cell acute lymphoblastic leukemia (ALL): results of a phase I study. Blood 2023; 142(suppl1): 966.
9) Martinelli G, Boissel N, Chevalier, Ottmann O, Gokbuget N, Rambaldi A, Ritchie EK, Papayannidis C, Tuglus CA, Morris JD, et al. Long-term follow-up of Blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia: final analysis of ALCANTARA study. Eur J Cancer 2021; 146: 107-114.
10) Topp MS, Stelljes M, Zugmaier G, Barnette P, Heffner LT, Trippett T, Duell J, Bargou RC,Holland C, Benjamin JE, et al. Blinatumomab retreatment after relapse in patients with relapsed/refractory B-precursor acute lymphoblastic leukemia. Leukemia 2018; 32: 562-565.
11) Locatelli F, Zugmaier G, Mergen N, Bader P, Jeha S, Schlegel PG, Bouquin JP, Handgretinger R, Brethon B, Rossig C, et al. Blinatumomabv in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis. Blood Adv 2022; 6: 1004-1013.
12) Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingbiel T, Parasole R, Linderkamp C, Flotho C, et al. Effect of Blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA 2021; 325: 843-854.
13) Locatelli F,Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingbiel T, Parasole R, Linderkamp C, Flotho C, et al. Improved survival and MRD remission with Blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL. Leukemia 2023; 37: 222-225.
14) Hogan LE, Brown PA, Ji L, Xu X, Devidas M, Bhatla T, Borwitz MJ, Raetz EA, Carroll A, Heerema NA, et al. Children's oncology group AALL1331: phase III trial of Blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. J Clin Oncol 2023; 41: 4118-4129.
15) Jabbour E, Haddad PG, Short NJ, et al. Phase 2 study of inotuzumab ozogamicin for measurable residual disease in acute lymphoblastic leukemia in remission. Blood 2024; 143: 417-421.
16) Fracchiolla NS, Sciumé M, Papayannidis C, Vitale A, Chiaretti S, Annunziata M, Giglio F, Salutari P, Forghieri F, Lazzarotto D, et al. Blinatumomab and inotuzumab ozogamicin sequential use for the treatment of relapsed/refractory acute lymphoblastic leukemia: a real-life campus A11 study. Cancers 2023; 15: 4623.
17) Jabbour E, Zugmaier G, Agrawal V, Martinez-Sanchez P, Rifon Roca J, Cassaday R, Boll B, Rijneveld A, Abdul-Hay M, Huguet F, et al. Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia. Am J Hematol 2024; 99: 586-595.
18) Queudeville M, Stein AS, Locatelli F, Ebinger M, Handgretinger R, Gokbuget N, Gore L, Zeng Y, Gokani P, Zugmaier G, et al. Low leukemia burden improves Blinatumomab with relapsed/refractory B-cell acute lymphoblastic leukemia. Cancer 2023; 129: 1384-1393.
19) Pillai V, Muralidharan K, Meng W, Bagashev A, Oldridge DA, Rosenthal J, Van Arnam J, Melenhorst JJ, Mohan D, DiNofia AM, et al. CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Adv 2019; 3: 3539-3549.
20) Shah RD, Cassaday RD, Park JH, Houot R, Oluwole OO, Logan AC, Boissel N, Leguay T, Bishop MR, Topp MS, et al. Subgroup analyses of KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) in ZUMA-3. HemaSphere 2022; 6: S3.
21) Myers RM, Taraseciviute A, Steinberg SM, Lamble AJ, Sheppard J, Yates B, Kovach AE, Wood B, Borowitz MJ, Stetler-Stevenson M, et al. Blinatumomab nonresponse and high disease burden are associated with inferior outcomes after CD19-CAR for B-ALL. J Clin Oncol 2022; 40: 932-944.
22) Lamble AJ, Myers RM, Taraseviciute A, John S, Yates B, Steinberg SM, Sheppard J, Kovach AE, Wood B, Borowitz MJ, et al. Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. Blood Adv 2023; 7: 575-584.
23) Gupta VK, Roloff GW, Muffly LS, Aldoss I, Kopmar NE, Lin C, Dekker SE, Jeyakumar N, O'Connor TE, Zhang A, et al. Impact of prior response to Blinatumomab on outcomes of brexucabtagene autoleucel (Brexu-cel) in adult patients with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL): results from the real-world outcomes collaborative of CAR-T in adult ALL (ROCCA). Blood 2023; 142(suppl 1): 2119.
24) Saygin C, Cannova J, Stock W and Muffly L. Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. Haematologica 2022; 107: 2783-2793.
25) Topp MS, Kufer P, Gokbuget N, Goebele M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmidt M, et al. Targeted therapy with the T-cell engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 2011; 29: 2493-2498.
26) Gokbuget N, Dombret H, Bonifacio M,Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood 2018; 131: 1522-1531.
27) Gokbuget N, Zugmaier G, Dombret H, Stein A, Bonifacio M, Graux C, Faul C, Bruggemann M, Taylor K, Mergen N, et al. Curative outcomes following Blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia. Leukemia&Lymphoma 2020; 61 : 2665-2673.
28) Gokbuget N, Kantarjian H, Bruggemann M, Stein AS, Bargou RC, Dombret H, Fielding AK, Heffner L, Rigal-Huguet F, Litzow M, et al. Molecular response with Blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Blood Adv 2019 ; 3 : 3033-3037.
29) Jabbour EJ, Short NJ, Jain N, Jammal N, Jogersen J, Wang S, Ohanian M, Alvarado Y, Kadia T, et al. Blinatumomab is associated with favorable outcomes in patients with B-cell lineage acute lymphoblastic leukemia and positive measurable residual disease at a threshold of 10-4 and higher. Am J Hematol 2022; 97: 1135-1141.
30) Cabannes-Hamy A, Brissot E, Leguay T, Huguet F, Chevallier P, Hunault M, Escoffre-Barbre M, Cluseau T, Balsat M, Nguyen S, et al. 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 GRAAL. Haematologica 2022; 107: 2072-2080.
31) Urbino I, Lengline E, Rabian F, Cerrano M, Kim R, Chevillon F, Ferrero D, Sebert M, Dhédin N, Itzykson R, et al. Blinatumomab consolidation for adult B-cell acute lymphoblastic leukemia in first and second complete remission. Blood Adv 2024, in press.
32) Litzow MR, Sun Z, Paietta E, Mattison RJ, Lazarus HM, Rowe JM, Arber DA, Mullighan CG, Willman CI, Zhang Y, et al. Consolidation therapy with Blinatumomab improves overall survival in newly diagnosed adult patients with B-lineage acute lymphoblastic leukemia in measurable residual disease negative remission; results from the ECOG-ACRIN E1910 randomized phase III national cooperative clinical trials network trial. Blood 2022; 140(suppl.1): LBA-1.
33) Litzow M, Sun Z, Mattison R, Paietta E, Mullighan C, Roberts K, Zhang Y, Racevskis J, Willman C, Wieduwilt M, et al. Consolidation with Blinatumomab improves overall and relapse-free survival in patients with newly diagnosed B-cell acute lymphoblastic leukemia: impact of age and MRD level in ECOG-ACRIN E1910. Hemasphere 2023; 7(33): EHA 2023 Hybrid Congress S115.
34) Luger SM, Sun Z, Mattison RJ, Paietta E, Roberts KG, Zhang Y, Racevckis J, Lazarus HM, Rowe JM, Arber DA, et al. Assessment of outcomes of consolidation therapy by number of cycles of Blinatumomab received in newly diagnosed measurable residual disease negative patients with B-lineage acute lymphoblastic leukemia: in the ECOG-ACRIN E1910 randomized phase III national clinical trials network trial. Blood 2023; 142(suppl.1): 2877.
35) Gu ME, Zhang JY, Tang YM, Xu WQ, Song H, Xu X. The effectiveness of Blinatumomab in clearing next-generation sequencing measurable residual disease in pediatric patients with B-cell acute lymphoblastic leukemia. Blood 2023; 142(suppl.1): 6076.
36) Stein AS, Kantarjian H, Gokbuget N, Bargou R, Litzow MR, Rambaldi A, Ribera JM, Zhang A, Zimnmerman Z,Zugmaier G, et al. Blinatumomab for acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation.
37) Gaballa MR, Banerjee P, Milton DR, Jiang X, Ganesh C, Khazal S, Nandivada V, Islam S, Kaplan M, Daher M, et al. Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia. Blood 2022; 139: 1908-1919.
38) Webster JA, Jones RJ, Blackford A, Shedeck A, Ambinder RF, Swinnen LJ, Wagner-Johnston N, Fuchs EJ, Bolanos-Meade J, Imus P, et al. A phase IB/II study of Blinatumomab in patients with B-cell acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (NHL) as post-allogeneic blood or marrow transplant (alloBMT) remission maintenance. Blood 2023; 142(suppl.1): 3582.
39) Chauvet P, Paviglianiti A, Labopin M, Labussiere H, Boissel N, Robin M, Maillard N, Ouachée-Chardin M, Forcade E, Poiré X, et al. Combining blinatumomab and donor lymphocyte infusion in B-ALL patients relapsing after allogeneic hematopoietic cell transplantation: a study of the SFGM-TC. Bone Marrow Transplant 2023; 58: 72-79.
40) Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowirtz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, et al. Effect of post-reinduction therapy consolidation with Blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA 325: 833-842.
41) LocatellI F, Eckert C, Hrusak O, Buldini B, Sartor M, Zugmaier G, Zeng Y, Pilankar D, Morris J, von Stackelberg A. Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high-.risk first relapse B-cell precursor acute lymphoblastic leukemia. Pediatr Blood Cancer 2022; 69: e29715.
42) Sayyed A, Chen C, Gerbitz A. Pretransplant blinatumomab improves outcomes in B cell acute lymphoblastic leukemia patients who undergo allogeneic hematopoietic transplantation. Transplant Cell Ther 2024; in press.
43) Llaurador G, Shaver K, Wu M, Wang T, Gillispei A, Doherty E, Craddock J, Read J, Yassine K; Morales E, et al. Blinatumomab therapy is associated with favorable outcomes after allogeneic hematopoietic cell transplantation in pediatric patients with B cell acute lymphoblastic leukemia. Transplant Cell Ther 2024; 30: 217-227.
44) Foa R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, Canichella M, Viero P, Ferrara F, Lunghi M, Fabbiano F, et al. Dasatanib-Blinatumomab for pH-posotive acute lymphoblastic leukemia in adults. N Engl J Med 2020; 383: 1613-1623.
45) Foa R, Bassan R, Elia L, Piciocchi A, Soddu S, Messina M, Ferrara F,m Lunghi M, Mulè A, Bonifacio M, Fracchiolla N, et al. Long-term results of the dasatanib-blinatumomab protocol for adult Philadelphia-positive ALL. J Clin Oncol 2024; 42: 8871-885.
46) Advani AS, Moseley A, O’Dwyer KM, Wood BL, Park J, Wieduwilt M, Jeyakumar D, Yaghmour G, Atallah EL, Gerds AT, et al. Dasatanib/prednisone induction followed by blinatumomab/dasatanib in Ph+ acute lymphoblastic leukemia. Blood Adv 2023; 7: 1279-1285.
47) Advani AS, Moseley A, O’Dwyer KM, Wood BL, Park J, Wieduwilt M, Jeyakumar D, Yaghmour G, Atallah EL, Gerds AT, et al. Long-term follow up for SWOG 1318: combination of dasatanib, prednisone, and Blinatumomab for older patients with Philadelphia-chromosome (Ph) positive acute lymphoblastic leukemia (ALL). Blood 2023; 142(suppl.1): 1499.
48) Geyer MB, Mascarenhas J, Smith M, pacsual S, shah A, Sivestrone MR, Czaplinska T, Johnson K, Thompson MC, Park JH. Chemotherapy-sparing induction followed by consolidation and maintenance with Blinatumomab and concurrent tyrosine kinase inhibitor therapy for newly-diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: primary endpoint results from the Bissphall study. Blood 2023; 142 (suppl.1): 1510.
49) Jabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Banerejee P, Rezvani K, Jiang X, Kim KH, Kanagal-Shamanna R, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukemia: a US, single-centre, single-arm, phase 2 trial. Lancet Hematol 2023; 10: e24-e34.
50) Haddad FJ, Jabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Kadia TM, Daver N, Nasnas C, Major E, et al. Chemotherapy-free combination of Blinatumomab and ponatinib in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: updates from a phase II trial. Blood 2023; 142(suppl.1): 2827.
51) Chiaretti S, Leoncin M, Elia L, Piciocchi A, Matarazzo M, Di Trani M, Sica S, Luppi M, Mancini V, Borlenghi E, et al. Comparison between dasatinib-blinatumomab vs ponatinib-blinatumomab chemo-free strategy for newly diagnosed Ph+ acute lymphoblastic leukemia patients. Preliminary results of the Gimema ALLL2820 trial. Blood 2023; 142(suppl.1): 4249.
52) Jabbour E, Kantarjian HM, Koller PB, Jamy O, Oehler VG, Lomaia E, Hunter AM, Uspenskaya O, Samarina S, Mukherjee S, et al. Update of olvermbatinib (HQP1351) overcoming ponatinib and/or asciminib resistance in patients (Pts) with heavily pretreated/refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2023; 142(suppl.1): 1798.
53) Li Z, Ting Z, Hu L, Duan W, Jiang Q. Olvermbatinib (HQP1351) combined with chemotherapy is an effective and safe treatment in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphoid blast phase (CMN-LBP) that failed TKI-based regimens. Blood 2023; 142(suppl.1): 5895.
54) Fan S, Wang L, Lu Y, Li Z. Olvermbatinib combined with Blinatumomab in treating T315I-mutated Philadelphia chromosome-positive acute lymphoblastic leukemia: two-case report. Ann Hematol 2024; 103: 525-532.
55) Zhang T, Zhu K, Zihong C, Lin R, Liu Q, Zhou H. Frontline combination of 3rd generation TKI Olvermbatinib and Blinatumomab for Ph+/Ph-like ALL patients. Blood 2023; 142(suppl.1): 1504.
56) Kantarjian H, Short NJ, Jain N, Sasaki K, Huang X, Haddad FG, Khouri I, DiNardo CD, Pemmaraju N, Wierda W, et al. Frontline combination of ponatinib and hyper-CVAD in Philadelphia chromosome-positive acute lymphoblastic leukemia: 80-months follow-up results. Am J Hematol 2023; 98: 493-501.
57) Jen WY, Jabbour E, Haddad FGF, Nasr L, Short NJ, Zoghbi M, Nasnas C, Issa GC, Yilmaz M, Daver N, et al. A phase II study of low-intensity chemotherapy (Mini-hyper-CVD) and ponatinib followed by Blinatumomab and ponatinib in patients with Philadelphia-positive acute lymphoblastic leukemia. Blood 2023; 142(suppl.1): 2868.
58) Schwartz M, McMahon CM, Amaya ML, Witkowski M, Pollkyea DA, Gutman JA, Minajuddin M, Smith C, Jordan CT. Consolidation with ponatinib plus sequential Blinatumomab and chemotherapy after low intensity dasatinib-based induction in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia: outcomes from a single institution. Blood 2023; 142(suppl.1): 4247.
59) Chiaretti S, Della Starza I, Santoro A, Spinelli O, Elia L, De Propris MS, Piccini M, Chiusolo P, Ferrara F, Zappasodi P, et al. Sequential chemotherapy and Blinatumomab to improve minimal residual disease in dult Ph- B-lineage acute lymphoblastic leukemia. Final results of the phase II GIMEMA LAL2317 trial. Blood 2023; 142(suppl.1): 826.
60) Tasian SK, Loh ML, Hunger SP. Philadelphia chromosome-like acute lymphoblastic leukemia. Blood 2017; 130: 2064-2072.
61) Boissel N, Huguet F, Graux C, Hicheri Y, Chevalier P, Kim R, Balsat M, Leguayt T, Hunault M, Maury S, et al. Frontline consolidation with Blinatumomab for high-risk Philadelphia-negative acute lymphoblkastic adult patients. Early results from the Graall-2014-QUEST phase 2. Blood 2021; 138(suppl.1): 1232.
62) Boissel N, Huguet F, Leguay T, Hunault M, Kim R, Hicheri Y, Chevallier P, Balsat M, Maury S, Thiebaut-Bertrand A, et al. Blinatumomab during consolidation in high-risk Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) adult patients : a two-cohorts comparison within the Graall-2014/B study. Blood 2022 ; 140(suppl.1) : 507-509.
63) Boissel N, Huguet F, Leguay T, Hunault M, Kim R, Hicheri Y, Passet M, Chevallier P, Balsat M, Maury S, et al. Exploring the heterogeneity of response to Blinatumomab in high-risk Philadephia-negative B-cell precursor acute lymphoblastic leukemia: an analysis from the QUEST sub-study of the Graall 2014/B trial. Blood 2023; 142(suppl.1): 499.
64) Fleming S, Reynolds J, Bajel A, Venn N, Kwan J, Moore J, Yeung D, Pati N, Lehy M, Nkyekyer J, et al Sequential Blinatumomab with reduced intensity chemotherapy in the treatment of older adults with newly diagnosed Ph negative B-precursor acute lymphoblastic leukemia-Interim analysis of the Australian Leukemia and Lymphoma group ALLo8 study. Blood 2021; 138(suppl.1): 1234.
65) Fleming S, Reynolds J, Bajel A, Venn N, Kwan J, Moore J, Yeung D, Pati N, Lehy M, Kollipara S, et al. Sequential Blinatumomab with reduced intensity chemotherapy for older adults with newly diagnosed Ph- B-precursor acute acute lymphoblastic leukemia- Final results of the ALLG ALL08 study. Hemasphere 2023; 7(suppl.1): e811479d.
66) Goekbuget N, Schwartz S, Faul C, Topp MS, Subklewe M, Renzelmann A, Stoltefuss A, Artenstein B, Wilke A; Raffel S, et al. Dose reduced chemotherapy in sequence with Blinatumomab for newly diagnosed patients with Ph/BCR:ABL negative B-cell precursor adult lymphoblastic leukemia 8ALL): preliminary results of the GMALL bold trial. Blood 2023; 142(suppl.1): 964.
67) Nguyen D, Kantarjian HM, Short NJ, Jain N, Haddad FG, Yilmaz M,Ferrajoli A, Kadia TM, Valero YA, Maiti A, et al. Updated results from a phase II study of hyper-CVAD, with or without inotuzumab ozogamicin, and sequential Blinatumomab in patients with newly diagnosed B-cell acute lymphoblastic leukemia. Blood 2023; 142(suppl.1): 4245.
68) Van der Sluis I, De Lorenzo P, Kotecha RS, Attarbaschi A, Escherich G, Nysom Stary J, Ferster A, Brethon B, Locatelli F, Schrappe M, et al. Blinatumomab added to chemotherapy in infant lymphoblastic leukemia. N Engl J Med 2023; 8: 1572-1581.
69) Schrappe M, Locatelli F, Valsecchi MG, Cario G, Vossen-Gajcy M, Stary J, Attarbaschi A, Bodmer N, Barbaric D, Elitzur S, et al. Pediatric patients with high-risk B-cell LL in first complete remission may benefit from less toxic immunotherapy with Blinatumomab – Results from randomized controlled phase 3 trial AIEOP-BFM ALL 2017. Blood 2023; 142(suppl.1): 825.