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. 2021 Apr;10(8):2601-2610.
doi: 10.1002/cam4.3731. Epub 2021 Mar 18.

Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Results of a pooled analysis

Max S Topp  1 , Anthony S Stein  2 , Nicola Gökbuget  3 , Heinz-August Horst  4 , Nicolas Boissel  5 , Giovanni Martinelli  6 , Hagop Kantarjian  7 , Monika Brüggemann  8 , Yuqi Chen  9 , Gerhard Zugmaier  10
Affiliations

Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Results of a pooled analysis

Max S Topp et al. Cancer Med. 2021 Apr.

Abstract

Blinatumomab is a BiTE® immuno-oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Aims To assess the efficacy and safety of blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & Methods Patient-level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). Results Compared with patients who received blinatumomab as second or later salvage, those who received blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26-1.97; P < .001) and relapse-free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98-1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41-0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. Discussion In this pooled analysis, the logistic regression analyses indicated greater benefit with blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. Conclusion Overall, blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage.

Keywords: BiTE®; acute lymphoblastic leukemia; blinatumomab; salvage; stem cell transplant.

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Conflict of interest statement

Max S. Topp: received fees for serving on the advisory boards of Amgen Inc., Regeneron, Affimed, Jazz Pharmaceuticals, Gilead Sciences, and Pfizer, and travel support from Amgen Inc., Roche, Regeneron, and Affimed.

Anthony S. Stein: participated in speakers’ bureau for Amgen Inc., Celgene, and Stemline.

Nicola Gökbuget: served on the advisory board and speakers’ bureau of, and received research funding from Amgen Inc.; served on the advisory board and speakers’ bureau of, and received travel support from Pfizer.

Heinz‐August Horst: received research funding, travel support from, and participated in advisory boards for Amgen Inc.; participated in advisory board for Pfizer, Jazz Pharmaceuticals, and Novartis; and received research funding from Regeneron.

Nicolas Boissel: provides consultancy to Amgen Inc.

Giovanni Martinelli: no disclosures.

Hagop Kantarjian: received research funding from AbbVie, Agios, Amgen Inc., Ariad, Astex, Bristol‐Myers Squibb, Cyclacel, Daiichi‐Sankyo, ImmunoGen, Jazz Pharmaceuticals, Novartis, and Pfizer; and received honoraria from AbbVie, Actinium, Agios, Amgen Inc., Pfizer, and Takeda.

Monika Brüggemann: received consulting fees and honoraria from Amgen Inc., Celgene, Incyte, Janssen, and Roche, and research funding from Affimed, Regeneron, and Roche.

Yuqi Chen is an employee of and owns stock in Amgen Inc.

Gerhard Zugmaier is an employee of, has patents from, and owns stock in Amgen Inc.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier estimated OS among patients who received blinatumomab as first salvage or second or later salvage in the overall population (A) or in subgroups by prior alloHSCT (yes vs. no; B). alloHSCT, allogeneic hematopoietic stem cell transplant; CI, confidence interval; OS, overall survival.
FIGURE 2
FIGURE 2
Kaplan–Meier estimated relapse‐free survival among patients who received blinatumomab as first salvage or second or later salvage. CI, confidence interval; OS, overall survival.
FIGURE 3
FIGURE 3
Kaplan–Meier estimated OS among patients who received blinatumomab as first salvage or second or later salvage followed by allogeneic hematopoietic stem cell transplant. CI, confidence interval; NE, not estimable; OS, overall survival.
See this image and copyright information in PMC

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