Abstract:
:Ixazomib, the first oral proteasome inhibitor (PI), has been approved for the treatment of relapsed refractory multiple myeloma (RRMM) in combination with lenalidomide and dexamethasone, based on the TOURMALINE-MM1 phase 3 trial, which demonstrated the efficacy and safety of this all-oral triplet, compared with lenalidomide-dexamethasone. However, clinical trial outcomes do not always translate into real-world outcomes. The aim of this study was to assess the outcomes of ixazomib-based combination for treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least one cycle of ixazomib-based treatment combination between June 2013 and June 2018 were identified. Data was extracted from medical charts focusing on demographics, disease characteristics, prior treatment, and responses. Primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), safety, and tolerability. A total of 78 patients across 7 sites were retrospectively included. Median follow-up was 22 months. Median age was 68 (range 38-90). Sixty-four percent received ixazomib in 2nd line, 19% in 3rd line. Overall, 89% of patients had been exposed to PIs (bortezomib 87%) prior to IRd, 41% to IMiDs. Twenty-nine (48%, of 60 available) had high (t(4:14), t(14:16), del17p) or intermediate (+1q21) risk aberrations. Most patients (82%) received ixazomib in combination with lenalidomide and dexamethasone. An exploratory assessment for disease aggressiveness at diagnosis was classified by a treating physician as indolent (rapid control to protect from target organ damage not required) vs aggressive (imminent target organ damage) in 63% vs 37%, respectively. Treatment was well tolerated, with a low discontinuation rate (11%). Median PFS on ixazomib therapy was 24 months (95% CI 17-30). PFS was 77% and 47% at 12 and 24 months, respectively. Median OS was not reached; OS was 91% and 80% at 12 and 24 months, respectively. Higher LDH, older age, and worse clinical aggressiveness were associated with worse PFS, whereas a deeper response to ixazomib (≥ VGPR) and a longer response to first-line bortezomib (≥ 24 m) were associated with an improved PFS on ixazomib. No effect on PFS was found for cytogenetic risk by FISH, ISS/rISS, and prior anti-myeloma treatment. Ixazomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting, regardless to cytogenetic risk, with a PFS of 24 months comparable with clinical trial data. This regimen had most favorable outcomes among patients who remained progression-free more than 24 months after a bortezomib induction and for those who have a more indolent disease phenotype.
journal_name
Ann Hematoljournal_title
Annals of hematologyauthors
Cohen YC,Magen H,Lavi N,Gatt ME,Chubar E,Horowitz N,Kreiniz N,Tadmor T,Trestman S,Vitkon R,Rouvio O,Shvetz O,Shaulov A,Ziv-Baran T,Avivi Idoi
10.1007/s00277-020-03985-9subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1273-1281issue
6eissn
0939-5555issn
1432-0584pii
10.1007/s00277-020-03985-9journal_volume
99pub_type
杂志文章,多中心研究abstract::Impact of FLT3 receptor tyrosine kinase activation via internal tandem duplication (ITD) of the juxtamembrane region on outcome of acute myeloid leukemia (AML) is still controversial. Recent researches reveal a role of FLT3 in monocyte differentiation in hematopoiesis. We analyzed the clinical impact of FLT3 alteratio...
journal_title:Annals of hematology
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journal_title:Annals of hematology
pub_type: 杂志文章
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journal_title:Annals of hematology
pub_type: 杂志文章,meta分析,评审
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journal_title:Annals of hematology
pub_type: 杂志文章
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journal_title:Annals of hematology
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journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
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journal_title:Annals of hematology
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journal_title:Annals of hematology
pub_type: 杂志文章,多中心研究
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pub_type: 临床试验,杂志文章,多中心研究
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