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Review
. 2024 Nov 19;14(1):203.
doi: 10.1038/s41408-024-01179-4.

Frontline Ph-negative B-cell precursor acute lymphoblastic leukemia treatment and the emerging role of blinatumomab

Elias J Jabbour  1 , Hagop M Kantarjian  2 , Nicola Goekbuget  3 , Bijal D Shah  4 , Sabina Chiaretti  5 , Jae H Park  6 , Anita W Rijneveld  7 , Lia Gore  8 , Shaun Fleming  9 , Aaron C Logan  10 , Josep M Ribera  11 , Tobias F Menne  12 , Khalid Mezzi  13 , Faraz Zaman  13 , Kelly Velasco  13 , Nicolas Boissel  14
Affiliations
Review

Frontline Ph-negative B-cell precursor acute lymphoblastic leukemia treatment and the emerging role of blinatumomab

Elias J Jabbour et al. Blood Cancer J. .

Abstract

This narrative review seeks to summarize chemotherapeutic regimens commonly used for patients with newly diagnosed Philadelphia (Ph) chromosome-negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in the frontline setting and to describe the latest clinical research using the bispecific T-cell-engaging immunotherapy blinatumomab in the first-line treatment setting. Current standard-of-care chemotherapeutic backbones for newly diagnosed Ph-negative BCP-ALL are based on the same overarching treatment principle: to reduce disease burden to undetectable levels and maintain lasting remission. The adult treatment landscape has progressively evolved following the adoption of pediatric-inspired regimens. However, these intense regimens are not tolerated by all, and high-risk patients still have inferior outcomes. Therefore, designing more effective and less toxic strategies remains key to further improving efficacy and safety outcomes. Overall, the treatment landscape is evolving in the frontline, and integration of blinatumomab into different standard frontline regimens may improve overall outcomes with a favorable safety profile.

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Conflict of interest statement

Competing interests EJJ has received research grants from Pfizer, Takeda, Amgen, AbbVie, Novartis, Astex, Adaptive Biotechnologies, and Ascentage and served as a consultant and on advisory boards for Pfizer, Takeda, Amgen, AbbVie, BMS, Novartis, Genentech, Adaptive Biotechnologies, and Ascentage. HMK has received/served as honoraria/advisory board/consulting for AbbVie, Amgen, Amphista, Ascentage, Astellas, Biologix, Curis, Ipsen Biopharmaceuticals, KAHR Medical, Labcorp, Novartis, Pfizer, Shenzhen Target Rx, Stemline, and Takeda and has received research grants from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, Jazz, and Novartis. NG has received institutional research funding from Amgen, Clinigen, Incyte, Jazz, Novartis, Pfizer, and Servier and received speaker honoraria or fees for advisory board participation from Amgen, AstraZeneca, Autolus, Celgene, Clinigen, Gilead, Incyte Jazz, Novartis, Pfizer, and Servier. BDS has served as a consultant and an educational advisor for Deciphera, Takeda, Kite, Novartis, Beigene, Pfizer, Jazz, BMS, Amgen, Adaptive, Lilly, Autolus, Syndax, Precision Biosciences, and Astra Zeneca; has received grants and served as an investigator for initiated trials for Kite, Jazz, and Servier; and has served on a data safety monitoring committee for Pepromene Bio. SC has served as a consultant and on advisory boards for Amgen, Incyte, Gilead, and AbbVie. JHP has received consulting fees from Affyimmune Therapeutics, Amgen, Autolus, Be Biopharma, Beigene, Bright Pharmaceutical Services, Caribou Biosciences, Curocell, Galapagos, In8Bio, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda; received honoraria from OncLive, Physician Education Resource, and MJH Life Sciences; served on scientific advisory boards of Allogene Therapeutics, Artiva Biotherapeutics and Green Cross Biopharma; and received institutional research funding from Autolus, Genentech, Fate Therapeutics, InCyte, Servier, and Takeda. AWR has no competing interest. LG is an unpaid advisor to Amgen on the development of oncology products in pediatric patients. SF has served as an advisory board member for Amgen, Astellas, Gilead/Kite, Jazz, Pfizer, and Jazz; received speakers’ honoraria from Amgen, BMS, Gilead/Kite, Jazz, Pfizer, and Novartis; and received research funding from Amgen. ACL has received consulting honoraria from Amgen, AbbVie, Actinium, Sanofi, and Takeda, and research funding from Amgen, Autolus, Incyte, Kadmon/Sanofi, Kite/Gilead, Pharmacyclics, and Talaris. JMR has served as a speaker for and received advisory board honoraria from Pfizer, Amgen, Shire, and Ariad; has received research support from and participated in clinical trials with Amgen; and has participated in clinical trials with Pfizer and Ariad. TFM has served on the advisory board for Amgen, Incyte, Gilead, Novartis, and Pfizer. KM, FZ, and KV are employees of and shareholders in Amgen. NB has received personal/consulting fees from Amgen, Gilead Sciences, Novartis, Servier, and Pfizer.

Figures

Fig. 1
Fig. 1. Comparing Phases of Therapy in Ph-Negative BCP-ALL Treatment Regimens: CALGB 10403 (US), hyper-CVAD (US, Australia), UKALLXII/ECOG E2993 (US), GRAALL-2014 (France), PETHEMA ALL-96 (Spain), GIMEMA LAL 1913 (Italy), HOVON-100 (Netherlands, Belgium), UKALL14 (UK), JALSG 202-0 (Japan).
Gray arrow represents induction phase, orange arrow represents consolidation phase, and gold arrow represents maintenance phase. Yellow text represents CNS prophylaxis. ALL acute lymphoblastic leukemia, BCP-ALL B-cell precursor acute lymphoblastic leukemia, CNS central nervous system, HD high dose, IT intrathecal, Ph Philadelphia chromosome.
Fig. 1
Fig. 1. Comparing Phases of Therapy in Ph-Negative BCP-ALL Treatment Regimens: CALGB 10403 (US), hyper-CVAD (US, Australia), UKALLXII/ECOG E2993 (US), GRAALL-2014 (France), PETHEMA ALL-96 (Spain), GIMEMA LAL 1913 (Italy), HOVON-100 (Netherlands, Belgium), UKALL14 (UK), JALSG 202-0 (Japan).
Gray arrow represents induction phase, orange arrow represents consolidation phase, and gold arrow represents maintenance phase. Yellow text represents CNS prophylaxis. ALL acute lymphoblastic leukemia, BCP-ALL B-cell precursor acute lymphoblastic leukemia, CNS central nervous system, HD high dose, IT intrathecal, Ph Philadelphia chromosome.
See this image and copyright information in PMC

References

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    1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia Version 2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 21, 2024. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
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