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Peripheral Blasts Are Associated with Response to Ruxolitinib and Outcome in Patients with Chronic-Phase Myelofibrosis
- Source :
- Blood. 138:3624-3624
- Publication Year :
- 2021
- Publisher :
- American Society of Hematology, 2021.
-
Abstract
- Background: The presence of peripheral blasts (PB) is a negative prognostic factor in patients (pts) with primary and secondary myelofibrosis (PMF/SMF) and PB ≥4% was associated with a particularly unfavorable prognosis (Masarova L et al, Cancer 2020). Ruxolitinib (RUX) is the JAK1/2 inhibitor most used for treatment of MF-related splenomegaly and symptoms. Its role has not been assessed in correlation with PB. Aims: To evaluate the impact of PB percentage on RUX efficacy and prognosis Methods: After IRB approval, the "RUX-MF" retrospective study collected 804 RUX-treated chronic-phase (CP, defined as PB Comparisons of quantitative variables between the 3 groups were carried out by Kruskal-Wallis and Dunn's tests while association between categorical variables was tested by the χ2 test. Variables significantly associated to RUX stop/leukemic transformation (LT)/overall survival (OS) in univariate analysis (Log-rank test) were considered for multivariable analyses, carried out using the Cox regression model, with evaluation of the model's performance in terms of goodness of fit. Results: Pts were categorized according to PB at RUX start: PB-0 (no PB; n. 487, 61.3%), PB-5 (PB 1-5%; n. 283, 35.8%), and PB-9 (PB 6-9%; n. 24, 2.9%). Pts characteristics at RUX start were: median age 68.1y (24-89); males 58.1%; PMF 52.5%; JAK2, CALR and MPL mutated: 80.5%, 13.1% and 2% (4.4% triple negative), high DIPSS: 7.6%; PLT25 x10 9/l: 10.8%/16.4%; spleen length ≥10 cm: 47.8%, TSS ≥20: 60.6%; ≥1/≥2 high-risk mutation (HMR): 69/18 out of 167 evaluable (41.3%/10.8%); fibrosis grade ≥2: 77.9%; starting/cumulative RUX dose ≥15 mg BID: 61.4%/52.6%. Higher PB count was associated to high DIPSS risk (PB-0: 1.9%, PB-5: 16.2%, PB-9: 21.7%, p At 3 and 6 mos, 26.9% and 30.4% of evaluable pts achieved a SR, while 59.7% and 68.1% were in SyR, respectively. At 3 mos, SR (PB-0: 31.8%, PB-5: 20.6%, PB-9: 10%, p=0.001) and SyR (PB-0: 62.9%, PB-5: 55.5%, PB-9: 36.8%, p=0.02) were less frequently achieved by PB-5 and PB-9 pts compared to PB-0 pts. This association remained significant for SR at 6 mos (PB-0: 35%, PB-5: 23.9%, PB-9: 14.3%, p=0.006) and for both SR (p=0.003) and SyR (p=0.01) at any time. After a median RUX exposure of 1.5 y (0.1-8.9), 491 (61.8%) pts stopped RUX, 110 (13.9%) had a LT and 365 (46%) died. In univariate analysis, at 2y PB-9 pts had higher rates of RUX stop (73.9% vs 40.8% and 34.3% in PB-5 and PB-0 pts, log-rank p In multivariable analysis, PB-9 pts confirmed their association with: 1) RUX stop (HR 3.74, 95%CI 1.51-3.70, p20 (HR 1.66, 95%CI 1.05-2.61, p=0.03), and HMR≥2 (HR 2.69, 95%CI 1.26-4.47, p=0.007); 2) LT (HR 3.71, 95%CI 1.71-8.04, p Conclusions: CP-MF pts with PB>5% have a worse response to RUX and a worse outcome. Personalized approaches beyond RUX monotherapy may be useful in this context. Further clinical trials evaluating combination strategies and new drugs are required. Figure 1 Figure 1. Disclosures Palandri: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AOP: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy. Abruzzese: Bristol Myers Squibb: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Iurlo: Bristol Myers Squibb: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Bonifacio: Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria. Cuneo: AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau. Lemoli: Celgene: Other: Support for attending meetings and/or travel; Jazz, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Daiichi Sankyo, Servier: Honoraria, Speakers Bureau. Cavo: Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria.
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi...........f372b6cbb018938143e8007e40bf4b17