Kooperativer Bibliotheksverbund

In: Oncology Research and Treatment, S. Karger AG, Vol. 38, No. 5 ( 2015), p. 221-229

Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The non-interventional study (NIS) NADIR was designed to assess the effectiveness and safety of lipegfilgrastim, a novel glycopegylated granulocyte-colony stimulating factor, in reducing the risk of both febrile and severe neutropenia. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Here, the interim analysis of NIS Nadir performed under real-world conditions at 80 oncology practices across Germany is reported. For a patient to be included, lipegfilgrastim at a subcutaneous single dose of 6 mg had to be administered during at least 1 cycle of the chemotherapy under consideration. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The interim analysis included 224 patients. Median patient age was 61.1 years (interquartile range 51.2-70.2 years). Main tumor type was breast cancer followed by lung cancer, and non-Hodgkin's lymphoma (46.0, 13.4, and 10.7%, respectively). When lipegfilgrastim was given as primary prophylaxis, no patient developed febrile neutropenia (FN). 1.3% of patients developed FN when primary prophylaxis was withheld. Only 68.6% of patients undergoing chemotherapy and at high risk ( 〉 20%) of developing FN were treated with lipegfilgrastim during the first cycle, exposing disparity between real-world practices and current treatment guidelines. Lipegfilgrastim was well tolerated. The only grade 3/4 treatment-related adverse event was anemia in 1 patient. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Lipegfilgrastim was effective and safe when administered for the prevention of chemotherapy-induced neutropenia under real-world conditions.

Type of Medium: Online Resource

ISSN: 2296-5270 , 2296-5262

URL: Article

DOI: 10.1159/000381631

Language: English

Publisher: S. Karger AG

Publication Date: 2015

detail.hit.zdb_id: 2749752-5

In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 165, No. 3 ( 2017-10), p. 721-731

Type of Medium: Online Resource

ISSN: 0167-6806 , 1573-7217

URL: Article

DOI: 10.1007/s10549-017-4365-7

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2004077-5

In: European Journal of Haematology, Wiley, Vol. 102, No. 2 ( 2019-02), p. 174-181

Abstract: The prospective non‐interventional study (NIS) NADIR was designed to evaluate both effectiveness and safety of prophylactic use of lipegfilgrastim (Lonquex ® ), a glycopegylated granulocyte colony‐stimulating factor, in cancer patients with different tumor entities undergoing chemotherapy in routine clinical practice. The primary objective was incidence of severe neutropenia, febrile neutropenia (FN), and neutropenia‐associated complications. Method NADIR was a national, multicenter, prospective NIS. Results Here, we present the data on patients with non‐Hodgkin lymphoma (NHL). Final analysis comprised 337 NHL patients having received ≥1 administration of lipegfilgrastim. Primary prophylaxis with lipegfilgrastim was documented in 78.7% of patients with high risk to develop FN. In total, ≥1 severe neutropenia (grade 3/4) was reported in 115 (34.1%) patients and ≥1 event of FN documented in 15 (4.5%) patients. Grade 3/4 infections were reported in 22 (6.5%) patients overall. Most frequently reported adverse events (AEs) related to lipegfilgrastim in total were bone pain (5.4%), leukocytosis (2.1%), back pain (1.8%), platelet count decreased (1.2%), and myalgia (1.2%). Fatal serious AEs were documented in 9 (2.7%) patients; none were attributable to lipegfilgrastim. Conclusion Prophylaxis or therapeutic intention with lipegfilgrastim in NHL patients in routine clinical practice showed similar effectiveness and safety as demonstrated in the pivotal trials.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.2019.102.issue-2

DOI: 10.1111/ejh.13189

Language: English

Publisher: Wiley

Publication Date: 2019

detail.hit.zdb_id: 2027114-1

In: European Journal of Haematology, Wiley, Vol. 101, No. 1 ( 2018-07), p. 115-118

Abstract: Recurrence of primary central nervous system lymphoma ( PCNSL ) after high‐dose chemotherapy with autologous stem cell transplantation ( ASCT ) usually has a poor overall prognosis with limited treatment options. Data on repeated ASCT are sparse. Checkpoint inhibitor maintenance therapy has also not been reported in PCNSL . Here, we report the first documented case of a successful third ASCT in second relapse of PCNSL . Whole‐exome sequencing identified a hypermutated tumor genotype. Additionally, immunohistochemistry on pretreatment tumor tissue revealed infiltrates of PD ‐1 + cytolytic T cells. These alterations provided a rationale for subsequent nivolumab maintenance treatment. Therapy led to a long‐term, ongoing complete remission. In eligible patients with recurrent MTX ‐sensitive PCNSL , multiple long‐term remissions can be induced by repetition of high‐dose MTX ‐based chemotherapy followed by autologous retransplantation. Subsequent immune checkpoint inhibitor maintenance therapy might be able to prolong or maintain remission.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.2018.101.issue-1

DOI: 10.1111/ejh.13072

Language: English

Publisher: Wiley

Publication Date: 2018

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5662-5662

Abstract: Introduction: Poor adherence and persistence to anticancer treatment are serious issues in the management of cancer patients since nonadherence has been shown to lead to higher treatment failure rates, worse outcome and higher total costs of care. The combination of the proteasome inhibitor carfilzomib (Kyprolis®) with lenalidomide (Revlimid®) and dexamethasone (CAR/LEN/DEX) or with dexamethasone alone (CAR/DEX) is approved for the treatment of patients with multiple myeloma who have received at least one prior therapy. According to the current approved schedule, carfilzomib has to be given twice weekly in both regimens. Real-world data on the implementation of this treatment recommendation are still limited. Methods: The prospective, multicenter, non-interventional, observational CARO study was designed to collect data on 300 patients with multiple myeloma (CAR/LEN/DEX: 200, CAR/DEX: 100) from 90 sites across Germany. Primary objective is patients' adherence and persistence to carfilzomib therapy as prescribed by the treating physician according to current Summary of Product Characteristics (SmPC). Secondary objectives are patients' adherence and persistence to lenalidomide and dexamethasone as well as the real-world implementation of the recommended CAR/LEN/DEX or CAR/DEX dosing regimen in clinical routine (i.e., the comparison of actually administered medication versus recommended medication according to current SmPC). Exploratory objectives are effectiveness, safety and health-related quality of life. The first interim analysis of the CARO study was scheduled to assess the primary and secondary endpoints 12 months after the recruitment of the first patient. Results: Between October 2016 and October 2017, 102 patients had been enrolled, thereof 68 patients into the CAR/LEN/DEX cohort and 32 patients into the CAR/DEX cohort at the time of the pre-specified interim analysis (database cut: 25 October 2017). Here, the focus is on the adherence of the twice weekly carfilzomib schedule in evaluable patients who received CAR/LEN/DEX (N=64) and on the implementation of the SmPC in terms of timing, dosing and frequency. Median age of patients was 72.3 years (range 43.4-84.3), 45.3% were female and 70.3% of the patients had a good performance status (PS) with a Karnofsky PS score of 80 to 100. The relative mean dose intensity of carfilzomib was 88.1%. 1368 of the scheduled 1591 carfilzomib administrations (86.0%) were given in time. 7.9% (n=125) of administrations were omitted, 5.0% (n=80) of administrations were delayed and 1.1% (n=18) of doses were administered earlier. Carfilzomib was omitted at least once in 43.8% of patients (n=28). 62.5% (n=40) and 18.8% (n=12) of patients, respectively, had a delayed or earlier carfilzomib administration documented at least once during their course of treatment. Reasons for deviations from the recommended carfilzomib dosing schedule concerning timing are depicted in Table 1. 1328 of 1466 carfilzomib administrations (90.6%) were given at the recommended dose. 6.2% (n=91) of doses were reduced. The main reason for dose reduction was the occurrence of adverse events (4.0%, n=58). Other reasons were: nonadherence (1.2%, n=18), organizational reasons (0.1%, n=2) and others (0.9%, n=13). 23.4% (n=15) of patients received at least one reduced carfilzomib dose during their course of treatment. The mean adherence to the carfilzomib dosing regimen (i.e., the percentage of doses administered as scheduled by the treating physician and not modified for adherence reasons) was 94.8%. Conclusion: According to our interim results, 86% of carfilzomib administrations were given in time and more than 90% of administrations were given at the recommended dose. Deviations from the recommended carfilzomib regimen were mainly due to safety issues or organizational reasons, but not due to nonadherence. Carfilzomib treatment adherence was almost 95%. Though, despite the required twice weekly dosing schedule, the carfilzomib regimen seems to be a convenient treatment option for multiple myeloma patients. Results have to be confirmed at final analysis. Disclosures Knauf: Celgene: Consultancy, Honoraria; Roche: Consultancy; Amgen: Consultancy, Honoraria; Mundipharma: Consultancy; Gilead Sciences: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Marschner:Amgen: Consultancy, Honoraria; IOMEDICO: Employment, Equity Ownership; Sandoz: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-117996

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4073-4073

Abstract: Introduction For patients (pts) with aggressive B-cell lymphoma immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) represents the standard of care with curative intention. For elderly pts a dose-reduced R-mini-CHOP protocol is feasible. No standard of care exists for frail or very old ( 〉 80 yrs) pts not eligible for CHOP-like treatment. Here we present the final results of the prospective DSHNHL-phase-2 trial for old or frail pts receiving Rituximab/Bendamustine (RB) for 1st-line treatment of aggressive B-cell lymphoma. Our goal was to determine feasibility, toxicity of the BR regimen in this pt cohort, and to determine which pts groups might potentially benefit from this reduced-intensity approach. Methods The open-label, multicenter, prospective, non-randomized phase-II trial "Subcutaneous Rituximab and Intravenous Bendamustine in very Elderly Patients or Elderly Medically Non Fit Patients ("Slow Go") with Aggressive CD20-positive B-cell Lymphoma" (B-R-ENDA, DSHNHL 2010-1, EudraCT 2010-024004-98) included all pts aged ≥81 yrs or 61-80 yrs and elevated CIRS 〉 6, not qualifying for R- CHOP, with histologically confirmed CD20+aggressive lymphoma of any Ann Arbor-stage and IPI score, and ECOG 〈 4 as determined during or after a prephase treatment. During run-in-phase, 20 pts received a prephase treatment of Prednisolone 100mg p.o. d-7 to -1, followed by Rituximab 375mg/m² i.v. on d-3, again followed by 7 cycles of Rituximab 375mg/m² i.v. on d1,q21 and 6 cycles of Bendamustine 90mg/m² i.v. on d1 and 2,q21. After a safety analysis, subsequent pts received prephase treatment with Rituximab 375mg/m² i.v. followed by 7 cycles of subcutaneous (s.c.) Rituximab 1400mg on d1,q21 and bendamustine as above. Primary endpoints were 2-year-progression-free survival (PFS) for efficacy (expected at 30-50% in the 〉 80 yr cohort), and treatment-associated deaths, frequency of grade 3/4 adverse events and SAEs, adherence to the protocol, complete and partial remission rate, rate of primary progression and relapse, and quality of life assessed by geriatric assessment and EORTC-QLQ-C30 for feasibility. Results: From 2012 to 2016, 68 pts (22 male, 46 female) were recruited in 24 centers into the trial and included into this intent-to-treat analysis (ITT). The median age was 81 yrs with 21% of pts older than 85 yrs. The median CIRS score was 8 and 72% had a CIRS 〉 6. The IPI was 〉 2 in 59% of pts. The patient population was per protocol divided into two subgroups: pts 61 to 80 yrs old and medically non-fit (29 pts) and pts older than 80 yrs (39 pts). For the 61 to 80 yrs old medically non-fit patients median age was 77 yrs (64-80), median CIRS score was 10 (2-22), IPI was 〉 2 in 76% of pts, 66% of pts had stage 3 or 4 disease, and ECOG was 〉 1 in 52% of pts. For the subgroup of pts 〉 80 yrs, median age was 84 yrs (81-95), median CIRS score was 7 (1-17), IPI was 〉 2 in 46% of pts, 51% of pts had stage 3 or 4 disease, and ECOG was 〉 1 in 23% of pts. 49% of pts received the complete treatment as planned (61-80 yrs: 38%; 〉 80 yrs: 56%). Reasons for early termination of treatment were PD in 15% (17%; 13%) and toxicity in 24% (24%; 23%) of pts. 29% 95% Confidence interval 19-42% of pts (38%; 23%) had grade 3-5 infections. Treatment related mortality was 15% (17%; 13%). Overall response rate (ORR) was 41% (28%; 51%) with 31% CR (10%; 46%). Median observation time was 29 months for EFS, PFS and OS. 2-yrs EFS was 23% (10%; 37%), PFS was 40% (32%; 45%), OS was 42% (37%; 46%). In a multivariate analysis adjusted for IPI factors elevated LDH and ECOG 〉 1 constituted the most significant risk factors for poor outcome. Conclusions: We describe a frail patient cohort with a median CIRS score of 8, with 72% pts with a CIRS 〉 6, considerable comorbidities and a high percentage of high-risk IPI. The primary efficacy endpoint (2 yr PFS 〉 80 yrs 45%) was met; for R-mini-CHOP, this was reported at 47% (Peyrade et al., Lancet Haemat, 2011). The IPI predicts outcome in the 〉 80 yrs cohort reliably. The RB regimen is active even in very elderly and frail pts up to 90 yrs of age. Therefore, in pts not eligible for full- or reduced dose R-CHOP treatment, it represents a tolerable and efficient alternative, albeit with a limited curative potential preferably in IPI low/intermediate-risk pts. Biomarker, comorbidity and QoL data will be analysed subsequently. Disclosures Zettl: Roche: Other: travel grants, Research Funding; Mundipharma: Research Funding. Viardot:Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Korfel:Mundipharma: Consultancy, Research Funding. Dreyling:Janssen: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Novartis: Other: scientific advisory board; Gilead: Consultancy, Other: scientific advisory board, Speakers Bureau; Sandoz: Other: scientific advisory board; Acerta: Other: scientific advisory board; Celgene: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: scientific advisory board, Research Funding, Speakers Bureau; Bayer: Consultancy, Other: scientific advisory board, Speakers Bureau. Illmer:Roche: Other: travel support. Schmitz:Novartis: Honoraria; Gilead: Honoraria; Celgene: Equity Ownership; Riemser: Consultancy, Honoraria. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding. Poeschel:Hexal: Speakers Bureau; Roche: Other: Travel support; Amgen: Other: Travel support; Abbvie: Other: Travel support; Astra Zeneca: Other: Travel support. Truemper:Takeda: Consultancy, Research Funding; Roche: Research Funding; Seattle Genetics, Inc.: Research Funding; Mundipharma: Research Funding; Janssen Oncology: Consultancy; Nordic Nanovector: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-122948

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1855-1855

Abstract: Abstract 1855 Introduction: Bortezomib and bendamustine have turned out to be effective, rapid action drugs in the treatment of multiple myeloma (MM). Bortezomib is a proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination with other cytostatic agents in MM. Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. The combination of bendamustine and prednisone with bortezomib (BPV) was assessed to determine the efficacy and toxicity of this regimen in patients with relapsed or refractory MM. Methods: Between January 2005 and December 2011, 78 patients (median age 62; range 31–81 years) with relapsed or refractory MM were treated with bendamustine 60 (–120) mg/qm on day 1 and 2, bortezomib 1.3 mg/qm on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11. Cycles were repeated every 21 days until maximum response or progressive disease. Maximum response was achieved if three weeks of therapy did not further reduce myeloma protein by more than 10 %. The median number of prior therapies was 2 (range 1–9). Previous therapies included 31 × thalidomide, 10 × lenalidomide, 14 × bortezomib, 24 × autologous PBSCT, and 19 × autologous-allogeneic PBSCT. In contrast to other clinical studies, patients with pronounced pancytopenia due to stem-cell toxic pre-treatment or advanced disease were also included. Patients were divided into two groups: group A (n = 45) comprised patients with normal bone marrow function and group B (n = 33) patients with pre-existing restricted bone marrow function and pronounced pancytopenia (CTC-Criteria grade III and IV). Patients were excluded from this retrospective analysis if they had other secondary malignancies. To exclude myelodysplastic syndroma or secondary acute myeloid leukemia cytological and cytogenetic examination of bone marrow was performed in patients with pre-existent severe pancytopenia. Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR). Results: The median number of BPV-treatment cycles was 2 (1–7). 54 patients (69 %) responded after at least one cycle of chemotherapy with 3 CR, 10 nCR, 10 VGPR, and 31 PR. Nine patients had MR, 9 patient's stable disease and 6 patients underwent progression. A follow up of surviving patients at a median of 34 months revealed median PFS and OS for patients without preexisting severe haematological toxicities (group A) of 11 months and 50 months respectively. Outcome was significantly better than that of patients with pre-existing severe haematological toxicities (group B) who had a median PFS, and OS of 3 months and 5 months, respectively (p 〈 0.001). The regimen was well-tolerated with few significant side effects in patients without preexisting severe haematological toxicities. New cytopenias occured infrequently with thrombocytopenia grade 3 in 11 patients, grade 4 in 8 patients and neutropenia grade 3 in 7 patients. Six patients experienced a moderate new polyneuropathy (grade 2). Summary: BPV therapy was well tolerated in patients with relapsed/refractory MM, with a response rate of approximately 70 %. The high efficacy and the favourable toxicity profile of BPV warrant further evaluation in clinical trials. Disclosures: Poenisch: Mundipharma: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.1855.1855

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 139, No. 3 ( 2013-3), p. 499-508

Type of Medium: Online Resource

ISSN: 0171-5216 , 1432-1335

URL: Article

DOI: 10.1007/s00432-012-1339-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2013

detail.hit.zdb_id: 1459285-X

In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 99, No. 9 ( 2020-09), p. 2085-2093

Abstract: Clinical research has resulted in an improvement of treatment options for patients with immune thrombocytopenia (ITP) over the last years. However, only few data exist on the real-life management of patients with ITP. To expand the knowledge, a multicenter, national survey was undertaken in 26 hematology practices distributed all over Germany. All patients with a diagnosis of ITP were documented using questionnaires, irrespective of the diagnosis date over a period of 2 years. Overall, data of 1023 patients were evaluated with 56% of patients being older than 60 years. Seventy-nine percent of the patients had chronic ( 〉  12 months), 16% persistent ( 〉  3–12 months), and 5% newly diagnosed (0–3 months) ITP. In 61% of cases, the disease lasted 3 or more years before survey documentation started. Main strategies applied as first-line therapy consisted of steroids in 45% and a “watch and wait” approach in 41% of patients. During second- and third-line strategies, treatment with steroids decreased (36% and 28%, respectively), while treatment modalities such as TPO-RAs increased (19% and 26%, respectively). As expected, patients with a low platelet count and thus a higher risk for bleeding and mortality received treatment (esp. steroids) more frequently during first line than those with a higher platelet count. Up to a third of patients were treated with steroids for more than a year. Overall, our study provides a cross-section overview about the current therapeutic treatment landscape in German ITP patients. The results will help to improve therapeutic management of ITP patients.

Type of Medium: Online Resource

ISSN: 0939-5555 , 1432-0584

URL: Article

DOI: 10.1007/s00277-020-04173-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 1458429-3

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 13-13

Abstract: Thrombosis is the major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). Age ≥60 years (y) and/or history of thrombosis labels patients (pts) as high-risk for thrombosis. Yet, thrombosis frequently occurs prior to the diagnosis of PV/ET. In a multicenter study of the East German Study Group (HINC-207; OSHO #091), the interaction between age and time occurrence of the first thrombosis as risk factors for thrombosis after diagnosis was studied. Methods After IRB approvals, JAK2 mutated adults with PV or ET were prospectively enrolled in 9 centers and centrally stratified in a one to two ratio (group A: pts with a history of thrombosis; group B: pts without thrombosis) with a pre-planned minimum of 60:120 pts. Based on a longitudinal and cross-sectional design, clinical and laboratory data at diagnosis, last follow-up, and thrombosis (for group A) were collected. Thrombosis prior to diagnosis was labeled as A1 and thrombosis after diagnosis as A2. Thrombosis risk factors were grouped into age-, previous thrombosis-, thrombosis prior to PV/ET-, cardiovascular (CV)-, thrombophilia-, and disease- (JAK2 allele burden, Hct, and WBC) related. Additionally, therapies [aspirin (ASS), anticoagulation, phlebotomy, and cytoreduction] and data from a study-own patient questionnaire were included. All pts signed informed consent. The primary endpoint was the phenotypic diversity in JAK2-mutated ET and PV pts with or without thrombosis. Results From April to Dec, 2019, 246 pts were recruited. Data on 237 pts (median age 62y; 59% females, 58% PV) are available. At diagnosis, pts in group A (n=71, median age 59.5y) tended to be younger than those in group B (n=166, median age 63y) (p=0.07). Yet, 70.4% thrombotic events (venous: median age 46.5y; arterial: median age 57y) occurred in A1 and correlated with younger age (p=0.03). Only 3 pts developed a second event after diagnosis. These were counted in A2 (n=24, median age at thrombosis: 61y). Overall, thrombosis occurred either prior to or within the first 3y after diagnosis in 63/71 (89%) pts. Age & gt;60y could not be identified as a risk factor for thrombosis or type of thrombosis at any time point. The 5 y probability of no thrombotic event after diagnosis in pts & gt;60y was 90.4% vs. 89.2% for pts & lt;60y (p=0.8) and that of a thrombotic event & gt;3y after diagnosis in pts & gt;60y was 3.7% vs. 4.9% for pts & lt;60y (p=0.7). Similarly, A1 did not correlate with A2 (p=0.3). With 1691 patient-years for the entire cohort, the incidence of thrombosis after PV/ET diagnosis was 0.7 for arterial and 0.6 for venous events per 100 patient-years. Smoking was more prevalent in pts & gt;60y (p=0.003) and was not associated with thrombosis. Irrespective of age, hypertension (65%, p=0.03), hyperlipidemia (19%, p=0.008), and diabetes (16.4%, p=0.05) were frequent and correlated with A2 while atrial fibrillation (p=0.03) and inherited thrombophilia risk factors (p & lt;0.00) with A1. JAK2 allele burden (median 19%) and Hct & gt;45% (median 45%) at diagnosis correlated strongly with age & gt;60y (p=0.005) but not with A, A1, or A2, although Hct & gt;45% at diagnosis correlated with A2 in PV (p=0.001). Surprisingly, a Hct & gt;45% at thrombosis was more frequently present in A1 (55%) vs A2 (30%) (p & lt;0.00). Median WBC at diagnosis was higher in B compared to A (p=0.004), strongly associated with age & gt;60y (p & lt;0.00) but not with A2. WBC & gt;15% at thrombosis did not correlate with A. Age rather than thrombosis was the trigger for cytoreduction [82% hydroxyurea (HU) in B pts & gt;60y vs 53% in A pts & lt;60y] (p & lt;0.00). In PV, ASS did not correlate with thrombosis (25% of pts in B did not receive ASS). Cytoreduction, interval between diagnosis and cytoreduction, nor the duration of exposure correlated with thrombosis. Conclusions: The majority of thrombotic events occurred prior to or within the first 3 years after the diagnosis of JAK2 mutated PV/ET and were associated with CV-risk factors rather than older age. Phenotypic features such as Hct & gt;45%, high WBC, and JAK2 allele burden were associated with age & gt;60y and less with thrombosis. Their value as surrogate markers for therapeutic interventions to reduce thrombosis needs to be critically evaluated in larger series. Whether adequate PV/ET- or CV-risk- treatments account for the low rate of CV events after diagnosis (despite a higher incidence of CV-risk factors) compared to the general population could not be answered due to study design and needs to be addressed prospectively. Disclosures Al-Ali: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-139366

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7