Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia

Rita Assi, Hagop Kantarjian, Nicholas J. Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour

Research output: Contribution to journalArticle

Abstract

Micro-Abstract The prognosis of patients with relapsed refractory Philadelphia chromosome–positive acute leukemia is considered poor. The combination of blinatumomab and a TKI resulted in high overall response rates among 13 patients. These results are promising and this strategy may minimize the use of chemotherapy in this setting. Objective The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy. Patients and Methods We retrospectively studied 12 adults with relapsed/refractory Ph+ acute lymphoblastic leukemia (n = 9) and chronic myeloid leukemia in blast crisis (n = 3), treated with the combination blinatumomab and a TKI (ponatinib, n = 8; dasatinib, n = 3; bosutinib, n = 1). All patients have previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse (n = 6) or persistent minimal residual disease following other regimens (n = 6). Results The complete hematologic, cytogenetic, and molecular response rates were 50% (3/6), 71% (5/7), and 75% (9/12), respectively. Two cases of grade 2 cytokine release syndrome were observed, all of which resolved with steroids and tocilizumab. No cardiovascular adverse events were encountered. With a median follow-up of 8 months, the median survival was not reached; the 6-month and 1-year overall survival rates were 73%. Conclusions The combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph+ disease. Prospective studies are warranted.

Original languageEnglish (US)
Pages (from-to)897-901
Number of pages5
JournalClinical Lymphoma, Myeloma and Leukemia
Volume17
Issue number12
DOIs
StatePublished - Dec 2017

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Philadelphia Chromosome
Protein-Tyrosine Kinases
Leukemia
Safety
Drug Therapy
Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Therapeutics
Blast Crisis
Stem Cell Transplantation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
blinatumomab
Survival Rate
Steroids
Monoclonal Antibodies
Prospective Studies
Cytokines
Recurrence
Survival

Keywords

  • ALL
  • Blinatumomab
  • CML
  • Philadelphia chromosome
  • Relapsed/refractory

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia. / Assi, Rita; Kantarjian, Hagop; Short, Nicholas J.; Daver, Naval; Takahashi, Koichi; Garcia-Manero, Guillermo; DiNardo, Courtney; Burger, Jan; Cortes, Jorge; Jain, Nitin; Wierda, William; Chamoun, Salim; Konopleva, Marina; Jabbour, Elias.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 17, No. 12, 12.2017, p. 897-901.

Research output: Contribution to journalArticle

Assi, R, Kantarjian, H, Short, NJ, Daver, N, Takahashi, K, Garcia-Manero, G, DiNardo, C, Burger, J, Cortes, J, Jain, N, Wierda, W, Chamoun, S, Konopleva, M & Jabbour, E 2017, 'Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia', Clinical Lymphoma, Myeloma and Leukemia, vol. 17, no. 12, pp. 897-901. https://doi.org/10.1016/j.clml.2017.08.101
Assi, Rita ; Kantarjian, Hagop ; Short, Nicholas J. ; Daver, Naval ; Takahashi, Koichi ; Garcia-Manero, Guillermo ; DiNardo, Courtney ; Burger, Jan ; Cortes, Jorge ; Jain, Nitin ; Wierda, William ; Chamoun, Salim ; Konopleva, Marina ; Jabbour, Elias. / Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia. In: Clinical Lymphoma, Myeloma and Leukemia. 2017 ; Vol. 17, No. 12. pp. 897-901.
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abstract = "Micro-Abstract The prognosis of patients with relapsed refractory Philadelphia chromosome–positive acute leukemia is considered poor. The combination of blinatumomab and a TKI resulted in high overall response rates among 13 patients. These results are promising and this strategy may minimize the use of chemotherapy in this setting. Objective The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy. Patients and Methods We retrospectively studied 12 adults with relapsed/refractory Ph+ acute lymphoblastic leukemia (n = 9) and chronic myeloid leukemia in blast crisis (n = 3), treated with the combination blinatumomab and a TKI (ponatinib, n = 8; dasatinib, n = 3; bosutinib, n = 1). All patients have previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse (n = 6) or persistent minimal residual disease following other regimens (n = 6). Results The complete hematologic, cytogenetic, and molecular response rates were 50{\%} (3/6), 71{\%} (5/7), and 75{\%} (9/12), respectively. Two cases of grade 2 cytokine release syndrome were observed, all of which resolved with steroids and tocilizumab. No cardiovascular adverse events were encountered. With a median follow-up of 8 months, the median survival was not reached; the 6-month and 1-year overall survival rates were 73{\%}. Conclusions The combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph+ disease. Prospective studies are warranted.",
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T1 - Safety and Efficacy of Blinatumomab in Combination With a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-positive Leukemia

AU - Assi, Rita

AU - Kantarjian, Hagop

AU - Short, Nicholas J.

AU - Daver, Naval

AU - Takahashi, Koichi

AU - Garcia-Manero, Guillermo

AU - DiNardo, Courtney

AU - Burger, Jan

AU - Cortes, Jorge

AU - Jain, Nitin

AU - Wierda, William

AU - Chamoun, Salim

AU - Konopleva, Marina

AU - Jabbour, Elias

PY - 2017/12

Y1 - 2017/12

N2 - Micro-Abstract The prognosis of patients with relapsed refractory Philadelphia chromosome–positive acute leukemia is considered poor. The combination of blinatumomab and a TKI resulted in high overall response rates among 13 patients. These results are promising and this strategy may minimize the use of chemotherapy in this setting. Objective The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy. Patients and Methods We retrospectively studied 12 adults with relapsed/refractory Ph+ acute lymphoblastic leukemia (n = 9) and chronic myeloid leukemia in blast crisis (n = 3), treated with the combination blinatumomab and a TKI (ponatinib, n = 8; dasatinib, n = 3; bosutinib, n = 1). All patients have previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse (n = 6) or persistent minimal residual disease following other regimens (n = 6). Results The complete hematologic, cytogenetic, and molecular response rates were 50% (3/6), 71% (5/7), and 75% (9/12), respectively. Two cases of grade 2 cytokine release syndrome were observed, all of which resolved with steroids and tocilizumab. No cardiovascular adverse events were encountered. With a median follow-up of 8 months, the median survival was not reached; the 6-month and 1-year overall survival rates were 73%. Conclusions The combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph+ disease. Prospective studies are warranted.

AB - Micro-Abstract The prognosis of patients with relapsed refractory Philadelphia chromosome–positive acute leukemia is considered poor. The combination of blinatumomab and a TKI resulted in high overall response rates among 13 patients. These results are promising and this strategy may minimize the use of chemotherapy in this setting. Objective The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy. Patients and Methods We retrospectively studied 12 adults with relapsed/refractory Ph+ acute lymphoblastic leukemia (n = 9) and chronic myeloid leukemia in blast crisis (n = 3), treated with the combination blinatumomab and a TKI (ponatinib, n = 8; dasatinib, n = 3; bosutinib, n = 1). All patients have previously failed at least 1 line of chemotherapy, including allogeneic stem cell transplantation, and 1 class of TKIs. Patients were treated for either overt hematologic relapse (n = 6) or persistent minimal residual disease following other regimens (n = 6). Results The complete hematologic, cytogenetic, and molecular response rates were 50% (3/6), 71% (5/7), and 75% (9/12), respectively. Two cases of grade 2 cytokine release syndrome were observed, all of which resolved with steroids and tocilizumab. No cardiovascular adverse events were encountered. With a median follow-up of 8 months, the median survival was not reached; the 6-month and 1-year overall survival rates were 73%. Conclusions The combination of blinatumomab with TKI is safe and effective in patients with relapsed/refractory Ph+ disease. Prospective studies are warranted.

KW - ALL

KW - Blinatumomab

KW - CML

KW - Philadelphia chromosome

KW - Relapsed/refractory

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