Skip to main content
Erschienen in: Annals of Hematology 1/2019

26.09.2018 | Original Article

Efficacy and safety of blinatumomab treatment in adult Korean patients with relapsed/refractory acute lymphoblastic leukemia on behalf of the Korean Society of Hematology ALL Working Party

verfasst von: Sung-Hoon Jung, Se-ryeon Lee, Deok-Hwan Yang, Seok Lee, Jae-Ho Yoon, Hyewon Lee, Soo-Mee Bang, Youngil Koh, Silvia Park, Dae Sik Kim, Ho-Young Yhim, Sung-Hyun Kim, Ji-Hyun Lee, Sang Kyun Sohn, Ik-Chan Song, Hong-ghi Lee, Jung-Won Cheong, Yunsuk Choi, Ho-Jin Shin

Erschienen in: Annals of Hematology | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Blinatumomab, a bispecific T cell-engaging antibody, has demonstrated efficacy for relapsed or refractory acute lymphoblastic leukemia (ALL). In this study, we evaluated the efficacy and toxicity of blinatumomab in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. A total of 50 patients received blinatumomab treatment between June 2016 and August 2017 in Korea. The median number of prior therapy was one (range, 1–4). Among the 49 evaluable patients, 22 (44.9%) achieved complete response (CR) or CR with incomplete blood count recovery, and 16 of whom subsequently underwent allogenic stem cell transplantation. Although no statistically significant differences were observed, patients with extramedullary disease and poor performance status had lower responses to blinatumomab treatment. In addition, the use of high-dose dexamethasone prior to blinatumomab treatment did not affect the response to blinatumomab. The median event-free survival and overall survival of the responders were 7.5 and 8.1 months, respectively. For non-hematologic toxicities, the most common toxicity was infection. The incidences of severe cytokine release syndrome and neurologic toxicity each was 4%. In conclusion, blinatumomab was an effective and tolerable therapy in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL.
Literatur
1.
Zurück zum Zitat Aldoss I, Song J, Stiller T, Nguyen T, Palmer J, O'Donnell M, Stein AS, Marcucci G, Forman S, Pullarkat V (2017) Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. Am J Hematol 92(9):858–865CrossRefPubMed Aldoss I, Song J, Stiller T, Nguyen T, Palmer J, O'Donnell M, Stein AS, Marcucci G, Forman S, Pullarkat V (2017) Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. Am J Hematol 92(9):858–865CrossRefPubMed
2.
Zurück zum Zitat Duell J, Dittrich M, Bedke T, Mueller T, Eisele F, Rosenwald A, Rasche L, Hartmann E, Dandekar T, Einsele H, Topp MS (2017) Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL. Leukemia 31(10):2181–2190CrossRefPubMedPubMedCentral Duell J, Dittrich M, Bedke T, Mueller T, Eisele F, Rosenwald A, Rasche L, Hartmann E, Dandekar T, Einsele H, Topp MS (2017) Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL. Leukemia 31(10):2181–2190CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Frey NV, Luger SM (2015) How I treat adults with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. Blood 126(5):589–596CrossRefPubMed Frey NV, Luger SM (2015) How I treat adults with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. Blood 126(5):589–596CrossRefPubMed
4.
Zurück zum Zitat Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M, the EUROCARE Working Group (2005) Childhood cancer survival trends in Europe: a EUROCARE working group study. J Clin Oncol 23(16):3742–3751CrossRefPubMed Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M, the EUROCARE Working Group (2005) Childhood cancer survival trends in Europe: a EUROCARE working group study. J Clin Oncol 23(16):3742–3751CrossRefPubMed
5.
Zurück zum Zitat Ge L, Ye F, Mao X, Chen J, Sun A, Zhu X, Qiu H, Jin Z, Miao M, Fu C, Ma X, Chen F, Xue S, Ruan C, Wu D, Tang X (2014) Extramedullary relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation: different characteristics between acute myelogenous leukemia and acute lymphoblastic leukemia. Biol Blood Marrow Transplant 20(7):1040–1047CrossRefPubMed Ge L, Ye F, Mao X, Chen J, Sun A, Zhu X, Qiu H, Jin Z, Miao M, Fu C, Ma X, Chen F, Xue S, Ruan C, Wu D, Tang X (2014) Extramedullary relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation: different characteristics between acute myelogenous leukemia and acute lymphoblastic leukemia. Biol Blood Marrow Transplant 20(7):1040–1047CrossRefPubMed
6.
Zurück zum Zitat Gokbuget N, Dombret H, Ribera JM, Fielding AK, Advani A, Bassan R, Chia V, Doubek M, Giebel S, Hoelzer D, Ifrah N, Katz A, Kelsh M, Martinelli G, Morgades M, OBrien S, Rowe JM, Stieglmaier J, Wadleigh M, Kantarjian H (2016) International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia. Haematologica 101(12):1524–1533CrossRefPubMedPubMedCentral Gokbuget N, Dombret H, Ribera JM, Fielding AK, Advani A, Bassan R, Chia V, Doubek M, Giebel S, Hoelzer D, Ifrah N, Katz A, Kelsh M, Martinelli G, Morgades M, OBrien S, Rowe JM, Stieglmaier J, Wadleigh M, Kantarjian H (2016) International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia. Haematologica 101(12):1524–1533CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Gokbuget N, Zugmaier G, Klinger M et al (2017) Long-term relapse-free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B-lineage acute lymphoblastic leukemia. Haematologica 102(4):e132–e135CrossRefPubMedPubMedCentral Gokbuget N, Zugmaier G, Klinger M et al (2017) Long-term relapse-free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B-lineage acute lymphoblastic leukemia. Haematologica 102(4):e132–e135CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Huehls AM, Coupet TA, Sentman CL (2015) Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol 93(3):290–296CrossRefPubMed Huehls AM, Coupet TA, Sentman CL (2015) Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol 93(3):290–296CrossRefPubMed
9.
Zurück zum Zitat Jung SH, Lee HJ, Vo MC, Kim HJ, Lee JJ (2017) Immunotherapy for the treatment of multiple myeloma. Crit Rev Oncol Hematol 111:87–93CrossRefPubMed Jung SH, Lee HJ, Vo MC, Kim HJ, Lee JJ (2017) Immunotherapy for the treatment of multiple myeloma. Crit Rev Oncol Hematol 111:87–93CrossRefPubMed
10.
Zurück zum Zitat Kantarjian H, Stein A, Gokbuget N et al (2017) Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 376(9):836–847CrossRefPubMedPubMedCentral Kantarjian H, Stein A, Gokbuget N et al (2017) Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 376(9):836–847CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Kohnke T, Krupka C, Tischer J et al (2015) Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab. J Hematol Oncol 8:111CrossRefPubMedPubMedCentral Kohnke T, Krupka C, Tischer J et al (2015) Increase of PD-L1 expressing B-precursor ALL cells in a patient resistant to the CD19/CD3-bispecific T cell engager antibody blinatumomab. J Hematol Oncol 8:111CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A (2017) 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 35(16):1795–1802CrossRefPubMed Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A (2017) 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 35(16):1795–1802CrossRefPubMed
13.
Zurück zum Zitat Nagorsen D, Baeuerle PA (2011) Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res 317(9):1255–1260CrossRefPubMed Nagorsen D, Baeuerle PA (2011) Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res 317(9):1255–1260CrossRefPubMed
14.
Zurück zum Zitat Pui CH, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC, Rubnitz JE, Razzouk BI, Howard SC, Hudson MM, Cheng C, Kun LE, Raimondi SC, Behm FG, Downing JR, Relling MV, Evans WE, Total Therapy Study XIIIB at St Jude Children's Research Hospital (2004) Improved outcome for children with acute lymphoblastic leukemia: results of total therapy study XIIIB at St Jude Children’s Research Hospital. Blood 104(9):2690–2696CrossRefPubMed Pui CH, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC, Rubnitz JE, Razzouk BI, Howard SC, Hudson MM, Cheng C, Kun LE, Raimondi SC, Behm FG, Downing JR, Relling MV, Evans WE, Total Therapy Study XIIIB at St Jude Children's Research Hospital (2004) Improved outcome for children with acute lymphoblastic leukemia: results of total therapy study XIIIB at St Jude Children’s Research Hospital. Blood 104(9):2690–2696CrossRefPubMed
15.
Zurück zum Zitat Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA (2013) Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 121(26):5154–5157CrossRefPubMedPubMedCentral Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA (2013) Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 121(26):5154–5157CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Topp MS, Gokbuget N, Stein AS et al (2015) Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 16(1):57–66CrossRefPubMed Topp MS, Gokbuget N, Stein AS et al (2015) Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 16(1):57–66CrossRefPubMed
17.
Zurück zum Zitat Topp MS, Gokbuget N, Zugmaier G, Degenhard E, Goebeler ME, Klinger M, Neumann SA, Horst HA, Raff T, Viardot A, Stelljes M, Schaich M, Kohne-Volland R, Bruggemann M, Ottmann OG, Burmeister T, Baeuerle PA, Nagorsen D, Schmidt M, Einsele H, Riethmuller G, Kneba M, Hoelzer D, Kufer P, Bargou RC (2012) Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 120(26):5185–5187CrossRefPubMed Topp MS, Gokbuget N, Zugmaier G, Degenhard E, Goebeler ME, Klinger M, Neumann SA, Horst HA, Raff T, Viardot A, Stelljes M, Schaich M, Kohne-Volland R, Bruggemann M, Ottmann OG, Burmeister T, Baeuerle PA, Nagorsen D, Schmidt M, Einsele H, Riethmuller G, Kneba M, Hoelzer D, Kufer P, Bargou RC (2012) Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 120(26):5185–5187CrossRefPubMed
18.
Zurück zum Zitat Wolach O, Stone RM (2015) Blinatumomab for the treatment of Philadelphia chromosome-negative, precursor B-cell acute lymphoblastic leukemia. Clin Cancer Res 21(19):4262–4269CrossRefPubMed Wolach O, Stone RM (2015) Blinatumomab for the treatment of Philadelphia chromosome-negative, precursor B-cell acute lymphoblastic leukemia. Clin Cancer Res 21(19):4262–4269CrossRefPubMed
19.
Zurück zum Zitat Zugmaier G, Gokbuget N, Klinger M, Viardot A, Stelljes M, Neumann S, Horst HA, Marks R, Faul C, Diedrich H, Reichle A, Bruggemann M, Holland C, Schmidt M, Einsele H, Bargou RC, Topp MS (2015) Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood 126(24):2578–2584CrossRefPubMedPubMedCentral Zugmaier G, Gokbuget N, Klinger M, Viardot A, Stelljes M, Neumann S, Horst HA, Marks R, Faul C, Diedrich H, Reichle A, Bruggemann M, Holland C, Schmidt M, Einsele H, Bargou RC, Topp MS (2015) Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood 126(24):2578–2584CrossRefPubMedPubMedCentral
Metadaten
Titel
Efficacy and safety of blinatumomab treatment in adult Korean patients with relapsed/refractory acute lymphoblastic leukemia on behalf of the Korean Society of Hematology ALL Working Party
verfasst von
Sung-Hoon Jung
Se-ryeon Lee
Deok-Hwan Yang
Seok Lee
Jae-Ho Yoon
Hyewon Lee
Soo-Mee Bang
Youngil Koh
Silvia Park
Dae Sik Kim
Ho-Young Yhim
Sung-Hyun Kim
Ji-Hyun Lee
Sang Kyun Sohn
Ik-Chan Song
Hong-ghi Lee
Jung-Won Cheong
Yunsuk Choi
Ho-Jin Shin
Publikationsdatum
26.09.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 1/2019
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3495-2

Weitere Artikel der Ausgabe 1/2019

Annals of Hematology 1/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.