Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study

Elias J. Jabbour, Nicola Gökbuget, Hagop M. Kantarjian, Xavier Thomas, Richard A. Larson, Sung Soo Yoon, Armin Ghobadi, Max S. Topp, Qui Tran, Janet L. Franklin, Stephen J. Forman, Anthony S. Stein

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Blinatumomab, a bispecific T-cell-engaging (BiTE®) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. Methods: In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Results: Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P =.68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status. Conclusions: Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Lay Summary: Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.

Original languageEnglish
Pages (from-to)4181-4192
Number of pages12
JournalCancer
Volume125
Issue number23
DOIs
StatePublished - 1 Dec 2019

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Hematopoietic Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transplantation
Standard of Care
Salvage Therapy
Drug Therapy
Survival
B-Lymphoid Precursor Cells
Residual Neoplasm
blinatumomab
Consolidation Chemotherapy
Stem Cell Transplantation
Therapeutics
Odds Ratio
Tissue Donors

Keywords

  • acute lymphoblastic leukemia
  • blinatumomab
  • refractory
  • relapsed
  • transplantation

Cite this

Jabbour, E. J., Gökbuget, N., Kantarjian, H. M., Thomas, X., Larson, R. A., Yoon, S. S., ... Stein, A. S. (2019). Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study. Cancer, 125(23), 4181-4192. https://doi.org/10.1002/cncr.32335
Jabbour, Elias J. ; Gökbuget, Nicola ; Kantarjian, Hagop M. ; Thomas, Xavier ; Larson, Richard A. ; Yoon, Sung Soo ; Ghobadi, Armin ; Topp, Max S. ; Tran, Qui ; Franklin, Janet L. ; Forman, Stephen J. ; Stein, Anthony S. / Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study. In: Cancer. 2019 ; Vol. 125, No. 23. pp. 4181-4192.
@article{4be9b04dec3542dea637044a495656e7,
title = "Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study",
abstract = "Background: Blinatumomab, a bispecific T-cell-engaging (BiTE{\circledR}) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. Methods: In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Results: Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P =.68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95{\%} CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status. Conclusions: Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Lay Summary: Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.",
keywords = "acute lymphoblastic leukemia, blinatumomab, refractory, relapsed, transplantation",
author = "Jabbour, {Elias J.} and Nicola G{\"o}kbuget and Kantarjian, {Hagop M.} and Xavier Thomas and Larson, {Richard A.} and Yoon, {Sung Soo} and Armin Ghobadi and Topp, {Max S.} and Qui Tran and Franklin, {Janet L.} and Forman, {Stephen J.} and Stein, {Anthony S.}",
year = "2019",
month = "12",
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Jabbour, EJ, Gökbuget, N, Kantarjian, HM, Thomas, X, Larson, RA, Yoon, SS, Ghobadi, A, Topp, MS, Tran, Q, Franklin, JL, Forman, SJ & Stein, AS 2019, 'Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study', Cancer, vol. 125, no. 23, pp. 4181-4192. https://doi.org/10.1002/cncr.32335

Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study. / Jabbour, Elias J.; Gökbuget, Nicola; Kantarjian, Hagop M.; Thomas, Xavier; Larson, Richard A.; Yoon, Sung Soo; Ghobadi, Armin; Topp, Max S.; Tran, Qui; Franklin, Janet L.; Forman, Stephen J.; Stein, Anthony S.

In: Cancer, Vol. 125, No. 23, 01.12.2019, p. 4181-4192.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study

AU - Jabbour, Elias J.

AU - Gökbuget, Nicola

AU - Kantarjian, Hagop M.

AU - Thomas, Xavier

AU - Larson, Richard A.

AU - Yoon, Sung Soo

AU - Ghobadi, Armin

AU - Topp, Max S.

AU - Tran, Qui

AU - Franklin, Janet L.

AU - Forman, Stephen J.

AU - Stein, Anthony S.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Background: Blinatumomab, a bispecific T-cell-engaging (BiTE®) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. Methods: In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Results: Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P =.68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status. Conclusions: Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Lay Summary: Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.

AB - Background: Blinatumomab, a bispecific T-cell-engaging (BiTE®) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. Methods: In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Results: Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P =.68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status. Conclusions: Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Lay Summary: Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.

KW - acute lymphoblastic leukemia

KW - blinatumomab

KW - refractory

KW - relapsed

KW - transplantation

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