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. 2019 Oct 22;3(20):3033-3037.
doi: 10.1182/bloodadvances.2019000457.

Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Nicola Gökbuget  1 , Hagop M Kantarjian  2 , Monika Brüggemann  3 , Anthony S Stein  4 , Ralf C Bargou  5 , Hervé Dombret  6 , Adele K Fielding  7 , Leonard Heffner  8 , Françoise Rigal-Huguet  9 , Mark Litzow  10 , Susan O'Brien  2 , Gerhard Zugmaier  11 , Shan Gao  12 , Dirk Nagorsen  13 , Stephen J Forman  4 , Max S Topp  14
Affiliations

Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Nicola Gökbuget et al. Blood Adv. .

Abstract

Minimal residual disease (MRD), where leukemic cell levels are lower than the morphologic detection threshold, is the most important prognostic factor for acute lymphoblastic leukemia (ALL) relapse during first-line chemotherapy treatment and is standard of care in treatment monitoring and decision making. Limited data are available on the prognostic value of MRD response after relapse. We evaluated the relationship between MRD response and outcomes in blinatumomab-treated adults with relapsed/refractory (R/R) B-cell precursor ALL. Of 90 patients with complete remission (CR) or CR with partial hematologic recovery (CRh), 64 (71.1%) achieved a complete MRD response (no detectable individual rearrangements of immunoglobulin/T-cell receptor genes by polymerase chain reaction [PCR] at a minimum sensitivity level of 10-4). Eleven patients had MRD <10-4. Therefore, overall, 75 (83.3%) experienced an MRD response (no detectable MRD or detectable MRD) measured by PCR within the first 2 treatment cycles. Overall survival (OS) and relapse-free survival (RFS) were significantly longer in patients who achieved CR/CRh and MRD response (median, 20.6 and 9.0 months, respectively) compared with CR/CRh patients without MRD response (median, 12.5 and 2.3 months, respectively). In conclusion, longer durations of OS and RFS associated with MRD response support the value of achieving MRD response and its use as a prognostic factor for blinatumomab treatment in R/R ALL. This trial was registered at www.clinicaltrials.gov as #NCT01466179.

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Conflict of interest statement

Conflict-of-interest disclosure: N.G. received research funding from Amgen, Pfizer, and Novartis; received advisory board and speaker fees from Amgen, Pfizer, and Novartis; received travel grants from Amgen, Pfizer, and Novartis; and received advisory board honoraria from Kite/Gilead and Celgene. H.M.K. received research funding from AbbVie, Agios, Amgen, Ariad, Astex, Bristol-Myers Squibb, Cyclacel, ImmunoGen, Jazz, and Pfizer and received honoraria from AbbVie, Actinium, Agios, Amgen, ImmunoGen, Orsinex, Pfizer, and Takeda. M.B. received research funding from Amgen; received reference diagnostics from Affimed, Amgen, and Regeneron; received consulting fees from PRMA Consulting, Ltd; and received speaker fees from Amgen, Hoffman-La Roche, Incyte, and Pfizer. A.S.S. received speaker fees from Amgen and Celgene. R.C.B. received fees for advisory activities from Amgen, AstraZeneca, Cellex, GEMoaB Monoclonals, GmbH, Molecular Partners, Novartis, and Pfizer; and has a blinatumomab patent with royalties paid. H.D. received research funding from Amgen, Incyte/Ariad, Novartis, Pfizer, and Servier; received consultancy fees from Amgen, Celgene, Cellectis, and Pfizer; received advisor honoraria from Amgen, Celgene, Cellectis, Incyte/Ariad, Novartis, Pfizer, Servier, and Shire/Baxalta; and received speaker fees from Amgen, Celgene, Incyte/Ariad, and Pfizer. L.H. received institutional research funding from AbbVie, ADC Therapeutics, Astex Pharmaceuticals, Genentech, and Pharmacyclics and received personal fees from Pharmacyclics. F.R.-H. received advisory board fees from Amgen, Bristol-Myers Squibb, Incyte, Jazz Pharmaceuticals, Novartis, and Pfizer. M.L. received research funding from Amgen. S.O. received consultancy fees from Amgen. G.Z. is an employee of Amgen and holds several pending patents. S.G. is a former employee of Amgen. D.N. is an employee and stockholder of Amgen and holds blinatumomab-related pending patents. M.S.T. received research funding and personal fees from Amgen. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Association of MRD response with outcome in patients with BCP-ALL after treatment with blinatumomab (full analysis set). Kaplan-Meier plots of OS (A), RFS (B), and DoR (C) in patients with hematologic CR/CRh and evaluable MRD assessments by MRD response (MRD-evaluable patients, n = 90). NE, not estimable.
See this image and copyright information in PMC

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