Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 1428-1428

Abstract: Introduction: Hyperleukocytosis, defined as a white blood cell count (WBC) of 〉 50 × 109/L or 〉 100 × 109/L, is seen in newly diagnosed AML and often results in leukostasis, increased risk of complications, and potentially early death. Those pts often require urgent evaluation and therapy. Leukapheresis is also sometimes used despite limited evidence supporting its use. There is limited data regarding the impact of time (day/night) and day (weekday/weekend) of admission and time to initiation of IC on outcomes in pts with hyperleukocytosis. Methods: Data were collected from 12 centers in USA and Europe (EU). Eligible pts had newly diagnosed AML, presented with a WBC 〉 50 × 109/L, and received IC. Univariate and multivariable logistic regression models stratified by centers (EU vs. USA) estimated odds ratios for death during induction (30-day mortality) and achievement of composite complete response (CRc) defined as CR+CR with incomplete count recovery (CRi). Univariate and multivariate Cox proportional hazard models stratified by centers (EU vs. USA) estimated hazards ratios (HR) for overall survival (OS). We evaluated the impact of leukapheresis, day of presentation (weekend vs. weekday), time of presentation (nighttime = 6pm-6am vs. daytime=6am-6pm), and time to initiation of IC. Studied covariates included age, Eastern Cooperative Oncology group performance status (ECOG PS), cytogenetics and molecular abnormalities, WBC, hemoglobin, platelet count, bone marrow and blood blast percentage, and presence of clinical leukostasis, tumor lysis syndrome (TLS) or disseminated intravascular coagulation (DIC) at presentation. Results: Among 1050 pts with AML and hyperleukocytosis whose data were collected, 787 were reported to have received IC and were included in this analysis. Of 787 pts receiving IC, 16.6% (95%CI, 13.9-19.3%) died during the first 30 days of IC. Leukapheresis was used in 117 pts (15%) in 8 of the 12 centers. In univariate analyses, neither weekend nor nighttime presentation nor use of leukapheresis impacted odds of death in the first 30 days. In multivariate analysis, higher odds of death during first 30 days were associated with age ³ 55 years (OR 3.2, p=0.015), ECOG PS ³ 2 (OR 4.4, 0.004), WBC 〉 100 × 109/L (OR 6.0, p=0.01) and presence of leukostasis (OR 4.5, p=0.005) and TLS (HR, 3.2, p=0.049). However, neither initiation of IC beyond 48 hours of presentation (vs. less than 48 hours) or use of leukapheresis significantly affected the odds of death in first 30 days (Figure 1A). Median OS of the entire cohort was 12.6 months (95%CI, 11.5-14.9) (Figure 2A). In multivariate analyses, age ³ 55 years (HR 2.6, p 〈 0.001), ECOG PS ³ 2 (HR 1.5, p=0.02), poor cytogenetic risk group (vs. intermediate/good, HR 1.6, p=0.02) and clinical presence of leukostasis (HR 1.4, p=0.03) all predicted inferior OS. The use of leukapheresis showed a trend towards improved OS with borderline statistical significance in univariate analysis (HR 0.77, 95%CI 0.6-1.0, p=0.052) (Figure 2B) but this was not statistically significant in multivariate analysis (Figure 1B). Initiation of IC beyond 48 hours of presentation (vs. less than 48 hours) did not significantly impact OS. CR was achieved in 51% (95%CI, 46.9%-54.1%) of pts and 14% (95%CI, 11.4%- 16.4%) had a CRi. In multivariate analysis, age ³ 55 years (OR 0.3, p 〈 0.001), ECOG PS ³ 2 (OR 0.5, p=0.012), adverse cytogenetic risk group (OR 0.4, p=0.007), and presence of leukostasis (OR 0.5, p=0.04) were associated with decreased odds of achieving CRc. However, initiation of IC beyond 48 hours of presentation (vs. less than 48 hours), and use of leukapheresis did not significantly impact odds of achieving CRc (Figure 1C). Day and time of presentation were not significantly associated with OS, 30-day mortality or CR/CRi rare in univariate analysis. Impact of leukapheresis in pts with clinical leukostasis and sensitivity analyses including propensity score matching are ongoing and will be presented at the meeting. Conclusions: In this very large international cohort of newly diagnosed AML pts who presented with hyperleukocytosis and treated with IC, neither day (weekend vs weekday) nor time (day vs night) nor the use of leukapheresis had significant impact on odds of death during the first 30 days or on OS. Our data further highlight the limited evidence behind use of leukapheresis and support the urgent need to conduct randomized clinical trials to study any of its benefits. Disclosures Montesinos: Novartis: Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau. Bhatt:Pfizer: Consultancy; CSL Behring: Consultancy; Incyte: Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Fathi:Celgene: Consultancy, Honoraria, Research Funding; Agios: Honoraria, Research Funding; Astellas: Honoraria; Boston Biomedical: Consultancy, Honoraria; Jazz: Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Khan:Teva: Speakers Bureau. Roboz:Janssen Pharmaceuticals: Consultancy; Bayer: Consultancy; Argenx: Consultancy; Astex Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; Eisai: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; Bayer: Consultancy; Aphivena Therapeutics: Consultancy; Orsenix: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Celltrion: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Aphivena Therapeutics: Consultancy; Jazz Pharmaceuticals: Consultancy; Orsenix: Consultancy; Jazz Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy; Roche/Genentech: Consultancy; Sandoz: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Cellectis: Research Funding; Cellectis: Research Funding; Otsuka: Consultancy; Otsuka: Consultancy; Celltrion: Consultancy; Celgene Corporation: Consultancy. Cluzeau:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Consultancy; Sanofi: Speakers Bureau. Germing:Novartis: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding. Mukherjee:LEK Consulting: Consultancy, Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Projects in Knowledge: Honoraria; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squib: Honoraria, Speakers Bureau; BioPharm Communications: Consultancy; Aplastic Anemia & MDS International Foundation in Joint Partnership with Cleveland Clinic Taussig Cancer Institute: Honoraria. Brunner:Novartis: Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. Ritchie:NS Pharma: Research Funding; Astellas Pharma: Research Funding; Bristol-Myers Squibb: Research Funding; ARIAD Pharmaceuticals: Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Incyte: Consultancy, Speakers Bureau. Podoltsev:Daiichi Snakyo: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas Pharma: Research Funding; Astex Pharmaceuticals: Research Funding; Celator: Research Funding; Boehringer Ingelheim: Research Funding; Pfizer: Research Funding; LAM Therapeutics: Research Funding; Sunesis Pharmaceuticals: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Gore:Celgene: Consultancy, Research Funding. Zeidan:AbbVie: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112495

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5173-5173

Abstract: Introduction: TP53 mutations have been associated with adverse outcomes in AML and MDS. While these mutations occur in less than 15-20% of pts, they are often associated with complex karyotypes and therapy-related (t)-myeloid neoplasms (MN). Previous studies showed poor outcomes with intensive chemotherapy (IC) and lower-intensity therapies [LIT] (e.g. hypomethylating agents [HMA] ), and higher relapse rates after allogeneic hematopoietic stem cell transplant (alloSCT), leaving the question of optimal treatment unanswered. Methods: We conducted a retrospective review of all adult pts with MN and pathogenic TP53 mutations who were treated at Yale University from 9/1/2015 to 5/31/2019. We collected data on age, sex, ethnicity, prior malignancies and their treatments, white blood cell (WBC), hemoglobin, platelet count, disease risk, initial and subsequent lines of therapies, and use of alloSCT. Responses were recorded using modified International Working Group (IWG) criteria 2003 for AML and 2006 for MDS. Overall survival (OS) was measured using Kaplan Meier methods. Results: We identified 83 pts with TP53-mutated MN (45 AML, 31 MDS, 4 chronic myelomonocytic leukemia, and 3 JAK2-positive myeloproliferative neoplasms). Median age was 69 years (range [R], 27-88 years), 52% were male, and 88% were Caucasian [Table 1] . Prior malignancy was noted in 35 pts (42%) and 29 (17 AML, 12 MDS) pts were classified as t-MN. Median WBC on presentation was 3 x 109 /L (R, 0.2 - 74x109) with a median of 0% peripheral blasts (R, 0-43%). Complex (n=75; 90%) and monosomal karyotypes (n=54; 65%) were highly prevalent. We identified 101 unique, pathogenic or likely pathogenic mutations in the TP53 gene with 17 pts harboring more than 1 abnormal variant (16 pts with 2 mutations, 1 pt with 4 mutations). Missense variants were most commonly encountered (n=82 variants, 81%) followed by splicesite (n=9, 9%), frameshift (n=6, 6%), and nonsense variants (n=4, 4.0%). 52 pts had isolated somatic TP53 variants (63%). Among the other 31 pts DNMT3A (n=8 pts), JAK2 (n=6), and TET2 (n=5) variants were the most common somatic mutations. Of note, targetable driver mutations such as FLT3 (n=0), IDH1 (n=3), and IDH2 (n=1) were very rare. Notably, pts with complex karyotype were more likely to have isolated TP53 mutations compared to non-complex karyotype pts (complex karyotype + isolated TP53 mutations: 51 pts [68.0%] vs non-complex karyotype + isolated TP53 mutations: 2 pts [25.0%] ; Fisher's exact test: p=0.024) [Table 2]. Median follow up of the cohort was 6.4 months (mos) [R: 0.2-55.3 mos] . Median OS in the entire study cohort was 7.6 mos (95% CI: 5.7-10.0 mos) with a 1-year OS rate of 30.5% (95% CI: 20.0-41.6%). Response rates and outcome for AML and MDS patients by treatment regimen are shown in Table 3. Among AML pts, IC did not appear to improve OS compared to pts receiving LIT (median OS 10.1 mos [95% CI: 6.4-15.5] vs 8.1 mos [95% CI: 1.9-13.6]; p=0.39). AML pts (median OS 6.7 mos [95% CI: 1.9-9.4] ; 1-year OS: 23.2% [95% CI: 11%-38%]) had a statistically non-significant trend to poorer outcomes compared to MDS pts (median OS 10 mos [95% CI 5.7-12.9] ; 1-year OS: 29.5% [95% CI 13.5-47.4%]; p=0.13). Notably, among the 10 pts who proceeded to alloSCT, only 3 pts relapsed after a median of 2.8 mos post-alloSCT. Relapse-free survival and median OS for pts who underwent alloSCT was not reached at a median follow up of 10.4 mos. Conclusions: In this case series we confirm the poor prognosis for pts with TP53-mutated MN. Median OS was only 7.6 mos, and IC did not appear to improve OS compared to LIT for AML pts. With limited follow-up, pts who underwent alloSCT appeared to benefit. Novel therapies are urgently needed to improve outcomes of this pt population. Disclosures Podoltsev: Kartos Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; AI Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding. Gore:Celgene Corporation: Consultancy, Research Funding. Prebet:Boehringer Ingelheim: Research Funding; Boehringer Ingelheim: Research Funding; Boehringer Ingelheim: Research Funding; pfizer: Honoraria; pfizer: Honoraria; pfizer: Honoraria; Tetraphase: Consultancy; novartis: Honoraria; novartis: Honoraria; Agios: Consultancy, Research Funding; novartis: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; pfizer: Honoraria; Genentech: Consultancy; pfizer: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; novartis: Honoraria; novartis: Honoraria. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Foss:Spectrum: Other: fees for non-CME/CE services ; Eisai: Consultancy; Acrotech: Consultancy; miRagen: Consultancy; Mallinckrodt: Consultancy; Seattle Genetics: Consultancy, Other: fees for non-CME/CE services . Huntington:AbbVie: Consultancy; Celgene: Consultancy, Research Funding; DTRM Biopharm: Research Funding; Pharmacyclics: Honoraria; Genentech: Consultancy; Bayer: Consultancy, Honoraria. Neparidze:Janssen Scientific Affairs, LLC: Research Funding; Eidos Therapeutics: Other: Member of Independent Diagnostic Committee; MMRF/Synteract: Membership on an entity's Board of Directors or advisory committees. Zeidan:Celgene Corporation: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria; Acceleron Pharma: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-127162

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 22 ( 2022-10), p. S128-

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(22)00761-3

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 21, No. 5 ( 2021-05), p. e483-e487

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/j.clml.2021.01.003

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1330-1330

Abstract: Introduction: While the use of immune checkpoint inhibitors (ICI) is now an established standard of care in the management of many solid tumors, the efficacy of this approach in myeloid neoplasms (MN) is still being explored. Preliminary data regarding efficacy presented to date are modest at best. Since many leukemia physicians lack extensive experience using ICI, and MN patients experience deep thrombocytopenia and bleeding risk precluding lung or colon biopsies to assess for immune-related adverse events (irAEs), MN presents a particularly difficult space for ICI development. Particular concern may center around distinguishing progressive infections (especially fungal) from immune pneumonitis and the appropriateness of steroids in such settings We report a single-center experience on the use of ICI in MN. Methods: We retrospectively analyzed data from patients (pts) with acute myeloid leukemia (AML) or higher-risk (International Prognostic Scoring System [IPSS] INT-2 or high-risk) myelodysplastic syndromes (MDS) treated with ICI therapy from April 16th, 2015 to June 3rd, 2019. We collected data on patient age, sex, race, Performance Status (ECOG PS), WBC, hemoglobin (Hgb), platelet count, serum metabolic and coagulation parameters, AML disease risk (cytogenetic and molecular) or MDS risk by IPSS score, prior lines of therapy (for refractory/relapsed [R/R] pts), ICI used (classified by targeted immune checkpoint to maintain trial confidentiality) as well as concurrent leukemia-directed therapy, irAEs, transfusion requirements, response to therapy and overall survival (OS). Results: Twenty-seven (13 AML and 14 MDS) pts received ICI in the context of clinical trials. Median age was 73 years, 63% were male, and 95% had an ECOG PS of 0 or 1 (Table 1). Nineteen pts (59%) had R/R disease, of whom 14 previously-received hypomethylating agent (HMA) therapy while 5 received intensive induction therapy. Median number of prior therapies was 1 (range [R], 1-3). Median follow-up was 11.3 months (R, 0.5-46.7). 54% of AML pts had cytogenetically or molecularly-defined poor risk disease; 86% of MDS pts had IPSS high-risk disease. Complex karyotype and TP53 mutation was noted in 35% and 35% of pts, respectively. (Table 1). Fifteen pts (56%) received a PDL1 inhibitor in combination with a HMA, while 4 (19%) pts received either a PD1 inhibitor in combination with a histone deacetylase inhibitor or CTLA4 inhibitor monotherapy. Two pts (7%) received dual ICI with both a PDL1 inhibitor and CTLA4 inhibitor (Table 1). The median number of ICI cycles administered was 4 with the main reason for discontinuation being lack of response (39%). Notably 27% discontinued because of intolerance to therapy. Almost half (n=12, 44%) of pts experienced an irAE; 4 pts had a grade 3 irAE. There were no grade 4 irAEs, but one patient with MDS developed multi-organ grade 3 irAEs and despite appropriate steroid therapy died due to irAEs with necrotizing myocarditis (with multifocal lymphocytic inflammatory infiltrate) and pericarditis confirmed on post-mortem examination. Of pts experiencing an irAE, 69% (including all pts with grade 3 irAEs) received high-dose corticosteroid therapy with a median time to initiation of 3 days (R, 1-14). No biopsies were performed due to bleeding risk in setting of cytopenia. Two of six newly-diagnosed AML pts achieved CR in response to ICI+HMA; one of 2 newly-diagnosed MDS pts developed CR following ICI+HMA. No R/R AML or MDS pts responded. Half of pts proceeded to an additional line of therapy after ICI. Two pts (7%) proceeded to allogeneic stem cell transplant (alloSCT), both receiving anti-CTLA4 monotherapy x 4 cycles with last cycle 62 and 400 days prior to alloSCT, respectively. One pt developed stage 1 acute graft versus host disease (GVHD) of gut with complete response to steroids and another with moderate, classic chronic GVHD without unusual GVHD. No AML pts in this study remain alive. Median OS for newly-diagnosed AML pts treated with ICI + HMA was longer than those with R/R disease (11.6 vs. 5.0 months) at a median follow-up of 11.6 months (Table 2). Conclusions: Patients with AML and MDS treated with ICI have a significant risk of irAEs requiring provider diligence and possibly quick and life-saving intervention. Larger prospective studies of ICI in AML and MDS patients are needed to better define the role of ICB in management of these cancers. Disclosures Podoltsev: Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AI Therapeutics: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Research Funding; Arog Pharmaceuticals: Research Funding; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; Samus Therapeutics: Research Funding; Kartos Therapeutics: Research Funding. Prebet:Genentech: Consultancy; Boehringer Ingelheim: Research Funding; pfizer: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; novartis: Honoraria; Boehringer Ingelheim: Research Funding; novartis: Honoraria; Tetraphase: Consultancy; novartis: Honoraria; pfizer: Honoraria; novartis: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; pfizer: Honoraria; Agios: Consultancy, Research Funding; novartis: Honoraria; pfizer: Honoraria; pfizer: Honoraria. Gore:Celgene Corporation: Consultancy, Research Funding. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Foss:Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; miRagen: Consultancy; Mallinckrodt: Consultancy; Spectrum: Other: fees for non-CME/CE services ; Acrotech: Consultancy; Eisai: Consultancy. Huntington:Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; AbbVie: Consultancy; Pharmacyclics: Honoraria; Genentech: Consultancy; DTRM Biopharm: Research Funding. Neparidze:Eidos Therapeutics: Other: Member of Independent Diagnostic Committee; MMRF/Synteract: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific Affairs, LLC: Research Funding. Zeidan:Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Seattle Genetics: Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; BeyondSpring: Honoraria; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: Immune checkpoint inhibitor therapy is not approved for use in patients with acute myeloid leukemia or myelodysplastic syndrome.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-127422

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 64, No. 1 ( 2023-01-02), p. 188-196

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428194.2022.2136952

Language: English

Publisher: Informa UK Limited

Publication Date: 2023

detail.hit.zdb_id: 2030637-4

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 22 ( 2022-10), p. S209-S210

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(22)01214-9

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Leukemia Research, Elsevier BV, Vol. 122 ( 2022-11), p. 106942-

Type of Medium: Online Resource

ISSN: 0145-2126

URL: Article

DOI: 10.1016/j.leukres.2022.106942

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2008028-1

In: Blood Advances, American Society of Hematology, Vol. 7, No. 5 ( 2023-03-14), p. 734-743

Abstract: Patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF), are known to have an increased risk of second malignancies (SMs). Hydroxyurea (HU) is a guideline-recommended cytoreductive therapy for patients at high risk for MPNs. Controversy exists as to whether HU use is associated with a higher risk of SMs, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We conducted a retrospective cohort study of older patients diagnosed with MPN (age ≥66 years) between 2010 and 2017 and included the data in the Surveillance, Epidemiology, and End Results Medicare-linked database. Multivariable competing risk analyses adjusting for patient characteristics were used to assess the impact of HU on the development of SM. We identified 4023 patients (1688 with PV, 1976 with ET, and 359 with MF) with a median age of 77 (interquartile range [IQR], 71-83) years at the time of MPN diagnosis. After a median follow-up of 3.25 (IQR, 2.10-5.00) years, 489 patients developed an SM (346 solid, 73 lymphoid, and 70 myeloid malignancies). The cumulative incidence probability of SM was 19.88% (95% confidence interval [CI] , 17.16%-22.75%) among 2683 HU users and 22.31% (95% CI, 17.51%-27.47%) among 1340 nonusers, respectively (Gray’s test, P  & lt; .01). We did not identify significant differences in the incidence of solid or hematologic SMs, including AML/MDS (hazard ratio, 1.33; 95% CI, 0.77-2.29; P = .30), between HU users and nonusers. Our results suggest that the use of HU does not increase the risk of SM in older patients with MPN.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2022008259

Language: English

Publisher: American Society of Hematology

Publication Date: 2023

detail.hit.zdb_id: 2876449-3

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 21, No. 6 ( 2021-06), p. 421-424.e2

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/j.clml.2021.01.010

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3