$Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy$
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Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy

Audrey M Sigmund,* Kieran D Sahasrabudhe,* Bhavana Bhatnagar Division of Hematology, Department of Internal Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA*These authors contributed equally to this workCorrespondence: Bhavana Bha...

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Autores principales:	Sigmund AM, Sahasrabudhe KD, Bhatnagar B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	blinatumomab bite antibody b-cell acute lymphoblastic leukemia relapsed and refractory disease measurable residual disease mrd Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/b11495eba1d74f478741d26b3469e17b
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spelling	oai:doaj.org-article:b11495eba1d74f478741d26b3469e17b2021-12-02T11:22:39ZEvaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy1179-9889https://doaj.org/article/b11495eba1d74f478741d26b3469e17b2020-11-01T00:00:00Zhttps://www.dovepress.com/evaluating-blinatumomab-for-the-treatment-of-relapsedrefractory-all-de-peer-reviewed-article-BLCTThttps://doaj.org/toc/1179-9889Audrey M Sigmund,* Kieran D Sahasrabudhe,* Bhavana Bhatnagar Division of Hematology, Department of Internal Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA*These authors contributed equally to this workCorrespondence: Bhavana BhatnagarOSU Wexner Medical Center, 320 W 10th Avenue Tel +1-614-688-7939Fax +1-614-293-6050Email Bhavana.Bhatnagar@osumc.eduAbstract: Although adults with B-cell acute lymphoblastic leukemia (B-ALL) achieve high complete remission (CR) rates following treatment with intensive multi-agent chemotherapy regimens, up to two-thirds of these patients eventually relapse. Unfortunately, adults with relapsed or refractory (R/R) B-ALL have a poor prognosis, with variable responses to salvage chemotherapy regimens and allogeneic stem cell transplant. As such, the need to develop effective and well-tolerated treatments for this patient population has been of paramount importance over the past decade. In this regard, treatment options for R/R B-ALL patients have expanded considerably over a relatively short period of time, with the approvals of blinatumomab, inotuzumab ozogamicin and tisagenlecleucel occurring within only the past six years. Blinatumomab, a CD19 x CD3 bispecific T-cell engager (BiTE) was the first of these immune therapies to receive approval, and for many patients, is used as first-line salvage therapy. A number of large clinical trials have demonstrated improved progression-free survival and overall survival for R/R B-ALL patients receiving blinatumomab as compared to those receiving conventional salvage chemotherapy. In addition to being approved for both Philadelphia chromosome-negative and Philadelphia chromosome-positive R/R B-ALL, blinatumomab is also the only ALL therapy that carries approval for the treatment of measurable residual disease (MRD). Although blinatumomab has changed the therapeutic landscape for adults with R/R B-ALL, a number of important clinical considerations and questions remain, including the potential role of blinatumomab in the frontline setting, mechanisms of resistance, optimal goal MRD level, the role of transplant following MRD clearance, the optimal place for blinatumomab in the context of other recently approved immune-mediated therapies, and real world outcomes for patients treated outside the context of clinical trials. These issues are the focus of ongoing studies, which will hopefully inform future clinical practice regarding the utility of blinatumomab in the treatment of B-ALL patients.Keywords: blinatumomab, BiTE antibody, B-cell acute lymphoblastic leukemia, relapsed and refractory disease, measurable residual disease, MRDSigmund AMSahasrabudhe KDBhatnagar BDove Medical Pressarticleblinatumomabbite antibodyb-cell acute lymphoblastic leukemiarelapsed and refractory diseasemeasurable residual diseasemrdDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol Volume 10, Pp 7-20 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	blinatumomab bite antibody b-cell acute lymphoblastic leukemia relapsed and refractory disease measurable residual disease mrd Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	blinatumomab bite antibody b-cell acute lymphoblastic leukemia relapsed and refractory disease measurable residual disease mrd Diseases of the blood and blood-forming organs RC633-647.5 Sigmund AM Sahasrabudhe KD Bhatnagar B Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy
description	Audrey M Sigmund,* Kieran D Sahasrabudhe,* Bhavana Bhatnagar Division of Hematology, Department of Internal Medicine, The Ohio State University and the Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA*These authors contributed equally to this workCorrespondence: Bhavana BhatnagarOSU Wexner Medical Center, 320 W 10th Avenue Tel +1-614-688-7939Fax +1-614-293-6050Email Bhavana.Bhatnagar@osumc.eduAbstract: Although adults with B-cell acute lymphoblastic leukemia (B-ALL) achieve high complete remission (CR) rates following treatment with intensive multi-agent chemotherapy regimens, up to two-thirds of these patients eventually relapse. Unfortunately, adults with relapsed or refractory (R/R) B-ALL have a poor prognosis, with variable responses to salvage chemotherapy regimens and allogeneic stem cell transplant. As such, the need to develop effective and well-tolerated treatments for this patient population has been of paramount importance over the past decade. In this regard, treatment options for R/R B-ALL patients have expanded considerably over a relatively short period of time, with the approvals of blinatumomab, inotuzumab ozogamicin and tisagenlecleucel occurring within only the past six years. Blinatumomab, a CD19 x CD3 bispecific T-cell engager (BiTE) was the first of these immune therapies to receive approval, and for many patients, is used as first-line salvage therapy. A number of large clinical trials have demonstrated improved progression-free survival and overall survival for R/R B-ALL patients receiving blinatumomab as compared to those receiving conventional salvage chemotherapy. In addition to being approved for both Philadelphia chromosome-negative and Philadelphia chromosome-positive R/R B-ALL, blinatumomab is also the only ALL therapy that carries approval for the treatment of measurable residual disease (MRD). Although blinatumomab has changed the therapeutic landscape for adults with R/R B-ALL, a number of important clinical considerations and questions remain, including the potential role of blinatumomab in the frontline setting, mechanisms of resistance, optimal goal MRD level, the role of transplant following MRD clearance, the optimal place for blinatumomab in the context of other recently approved immune-mediated therapies, and real world outcomes for patients treated outside the context of clinical trials. These issues are the focus of ongoing studies, which will hopefully inform future clinical practice regarding the utility of blinatumomab in the treatment of B-ALL patients.Keywords: blinatumomab, BiTE antibody, B-cell acute lymphoblastic leukemia, relapsed and refractory disease, measurable residual disease, MRD
format	article
author	Sigmund AM Sahasrabudhe KD Bhatnagar B
author_facet	Sigmund AM Sahasrabudhe KD Bhatnagar B
author_sort	Sigmund AM
title	Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy
title_short	Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy
title_full	Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy
title_fullStr	Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy
title_full_unstemmed	Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy
title_sort	evaluating blinatumomab for the treatment of relapsed/refractory all: design, development, and place in therapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/b11495eba1d74f478741d26b3469e17b
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Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy

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