> Details
Rohmer, Julien;
Groh, Matthieu;
Trichereau, Julie;
Panel, Kewin;
Preudhomme, Claude;
Legrand, Fanny;
Ackermann, Felix;
Couteau-Chardon, Amélie;
Ebbo, Mikael;
Fain, Olivier;
Galicier, Lionel;
Hamidou, Mohamed;
Hunault, Mathilde;
Lengline, Etienne;
Mohr, Catherine;
Nicolini, Franck E;
Rey, Jerome;
Terriou, Louis;
Morati Hafsaoui, Chafika;
Tavitian, Suzanne;
Machelart, Irene;
Jondeau, Katayoun;
Arnulf, Bertrand;
Ianotto, Jean-Christophe;
[...]
Clinical Spectrum, Long-Term Outcomes and Predictors of Relapse after Imatinib Discontinuation in FIP1L1-Pdgfra-Associated Chronic Eosinophilic Leukemia: Data from 150 Patients
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- Media type: E-Article
- Title: Clinical Spectrum, Long-Term Outcomes and Predictors of Relapse after Imatinib Discontinuation in FIP1L1-Pdgfra-Associated Chronic Eosinophilic Leukemia: Data from 150 Patients
- Contributor: Rohmer, Julien; Groh, Matthieu; Trichereau, Julie; Panel, Kewin; Preudhomme, Claude; Legrand, Fanny; Ackermann, Felix; Couteau-Chardon, Amélie; Ebbo, Mikael; Fain, Olivier; Galicier, Lionel; Hamidou, Mohamed; Hunault, Mathilde; Lengline, Etienne; Mohr, Catherine; Nicolini, Franck E; Rey, Jerome; Terriou, Louis; Morati Hafsaoui, Chafika; Tavitian, Suzanne; Machelart, Irene; Jondeau, Katayoun; Arnulf, Bertrand; Ianotto, Jean-Christophe; [...]
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Published:
American Society of Hematology, 2019
- Published in: Blood, 134 (2019) Supplement_1, Seite 840-840
- Language: English
- DOI: 10.1182/blood-2019-130009
- ISSN: 0006-4971; 1528-0020
- Keywords: Cell Biology ; Hematology ; Immunology ; Biochemistry
- Origination:
- Footnote:
- Description: Introduction. Cases series of patients with FIP1L1-PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P+ CEL) are scarce and of small sample-size. Low-dose imatinib mesylate (IM) is highly effective in this setting. Although successful treatment discontinuation has been reported, approximately 40% of the patients subsequently relapse. To date, no predictor of relapse after IM discontinuation has yet been evidenced. Methods. We conducted a French multicentric retrospective of patients diagnosed with F/P+ CEL between 2003-2019. Weight loss was defined as a 10% weight loss over the course of the disease's history. Complete (CHR) and partial (PHR) hematological responses were defined as a normalization of the absolute eosinophil count (AEC) and as a reduction in peripheral blood eosinophilia by at least 50% from baseline, respectively. Relapses were defined as the recurrence of eosinophilia, with or without evidence of F/P-gene transcript, but without any other explanation. Complete molecular response (CMR) was defined as a negative RT-PCR and/or RQ-PCR assay for F/P rearrangement. A backward stepwise logistic regression model was used to identify factors associated with relapse after IM discontinuation. Results. One hundred and fifty F/P+ CEL patients (145 males; mean (SD) age at diagnosis: 49 (+/-12 years) were included, among which 26 (17%) did not report any symptom. The main involved organs were the spleen (n=65, 43%), skin (n=47, 31%), heart (n=27, 18%), lungs (n=36, 24%), central nervous system (n=14, 9%), and bones/joints (n=8, 5%). Four (2,6%) patients showed features of vasculitis, involving the skin (n=2) and the CNS (n=2). The mean peak AEC was 10.3 G/L (+/-6 G/l). Besides eosinophilia, the most frequent associated complete blood count (CBC) abnormalities were thrombocytopenia (n=43, 28%), anemia (n=37, 24%), hyperleukocytosis (n=33, 22%) and monocytosis (n=25, 16%). Forty-seven (31%) patients had normal CBC besides eosinophilia. Bone marrow karyotype was normal in 91% (when tested, n=94). Serum vitamin B12 and tryptase (mean: 2386 (+/-1435) pmol/L and 34 (+/-20) µg/L) levels were elevated in 74 (94%) and 44 (79%) of patients respectively, whereas CRP and IgE levels were elevated in 31 (26%) and 12 (14%) each. None of the 37 (25%) patients that received first-line glucocorticoid therapy achieved CHR. All but 3 patients received IM (daily starting dose: 100 (n= 102; 72%), 200 (n=13; 9%) or 400 mg (n=20; 14%)), of whom 100% and 99% achieved CHR and CMR (when tested: n=84), respectively. The mean follow-up (FU) was 80 (+/- 56) months, with overall survival at 1, 5 and 10 years of 99%, 95% and 84% (reaching 100%, 98% and 89% in the 147 IMB-treated patients) respectively. Overall, 8 (5%) patients died during FU, including untreated patients with acute myeloblastic leukemia transformation (n=2) and a single patient with massive cerebral infarction. Eight patients relapsed during IM tapering, all of which were successfully treated when higher doses of IM were resumed. After a median [IQR] of 44 [27-72] months of IM treatment, 46 (32%) patients eventually discontinued IM, amongst whom 19 (41%) relapsed after a median of 10[4-23] months (42% of relapses defined by PCR). In multivariate analysis, weight loss (HR: 5,02 95%CI[1,9 - 28,04]; p =0,004), the time between onset of eosinophilia and IM initiation (HR 1,02 [1,00 - 1,03]; 0,01) and duration of IM treatment prior to discontinuation (HR: 0,97 [0,95-0,99]; p=0,01) were independent factors of relapse (Table 1). Conclusion. This large cohort further confirms that F/P+ CEL almost exclusively affects male patients, with spleen, skin, heart and lung involvements being the most frequent. While glucocorticoids never lead to the normalization of CBC parameters, IM is highly effective and treated patients carry an excellent prognosis. After IM discontinuation, although 60% of patients maintain CHR overtime, 40% subsequently relapse, with weight loss, time between onset of eosinophilia and IM initiation and duration of IM treatment prior to discontinuation being significant but moderate independent factors of relapse. Disclosures Nicolini: Incyte Biosciences: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Sun Pharma Ltd: Consultancy. Tavitian:Novartis: Membership on an entity's Board of Directors or advisory committees. Huguet:Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte Biosciences: Honoraria; Amgen: Honoraria; Servier: Honoraria; Jazz Pharmaceuticals: Honoraria. Jardin:Servier: Honoraria; janssen: Honoraria; celgene: Honoraria; roche: Honoraria; amgen: Honoraria.
- Access State: Open Access