Blinatumomab administered concurrently with oral tyrosine kinase inhibitor therapy is a well-tolerated consolidation strategy and eradicates measurable residual disease in adults with Philadelphia chromosome positive acute lymphoblastic leukemia Journal Article

   

Authors:	King, A. C.; Pappacena, J. J.; Tallman, M. S.; Park, J. H.; Geyer, M. B.
Article Title:	Blinatumomab administered concurrently with oral tyrosine kinase inhibitor therapy is a well-tolerated consolidation strategy and eradicates measurable residual disease in adults with Philadelphia chromosome positive acute lymphoblastic leukemia
Abstract:	Incorporation of ABL-targeted oral tyrosine kinase inhibitors (TKIs) into frontline therapeutic regimens has improved outcomes for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, patients with persistent minimal residual disease (MRD) exhibit increased risk of relapse. Combining consolidative chemotherapy with TKIs may increase rates of infectious complications, organ toxicity, hospitalization, and non-relapse mortality. Blinatumomab has demonstrated single-agent activity in patients with relapsed B-ALL or persistent MRD, including Ph + B-ALL. We have used blinatumomab concomitantly with commercially available TKIs as consolidative therapy to spare toxicities of conventional chemotherapy. We evaluated 11 adults with previously treated Ph + B-ALL who received blinatumomab concurrent with TKI (ponatinib, n = 5; dasatinib, n = 4; nilotinib, n = 1; imatinib, n = 1) to eradicate MRD or sustain MRD-negativity. Eight of 9 patients with MRD achieved BCR-ABL1 negativity (complete molecular response, CMR) after a median of one cycle; 2/2 patients without measurable disease durably maintained CMR. Cytokine release syndrome (all grade 1–2) was observed in 3/11 patients; one patient experienced transient grade 1 neurologic toxicity. Transient grade 2 transaminitis was observed in 6/11 patients, including 4/5 recipients of blinatumomab + ponatinib. This small series suggests blinatumomab + TKI is a safe and effective consolidation strategy for patients with Ph + ALL to achieve or maintain CMR. © 2019 Elsevier Ltd
Keywords:	adult; cancer chemotherapy; clinical article; controlled study; treatment response; aged; middle aged; drug tolerability; cancer recurrence; drug efficacy; drug safety; treatment duration; neurotoxicity; recurrence risk; follow up; imatinib; multiple cycle treatment; dasatinib; acute lymphoblastic leukemia; protein tyrosine kinase inhibitor; drug dose escalation; minimal residual disease; clinical evaluation; clinical effectiveness; drug dose titration; tyrosine kinase inhibitor; nilotinib; hypertransaminasemia; cytokine release syndrome; philadelphia chromosome positive cell; blinatumomab; ponatinib; disease burden; human; male; female; priority journal; article; disease eradication
Journal Title:	Leukemia Research
Volume:	79
ISSN:	0145-2126
Publisher:	Elsevier Ltd
Date Published:	2019-04-01
Start Page:	27
End Page:	33
Language:	English
DOI:	10.1016/j.leukres.2019.02.009
PUBMED:	30831480
PROVIDER:	scopus
PMCID:	PMC7536787
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062181215&doi=10.1016%2fj.leukres.2019.02.009&partnerID=40&md5=7b3acbdc552cbf0cba911160768a71f3
Notes:	Article -- Export Date: 1 April 2019 -- Source: Scopus

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