Clinical and Biological Features in Patients with Ph-Negative Chronic Myeloproliferative Neoplasm Showing Different Molecular Pattern. Comparative Study in 596 Patients of the Registro Italiano Trombocitemie (RIT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4071-4071
Author(s):  
Luigi Gugliotta ◽  
Alessandra Iurlo ◽  
Gabriele Gugliotta ◽  
Alessia Tieghi ◽  
Giorgina Specchia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Myeloproliferative Neoplasm ◽  
Thrombotic Risk ◽  
Biological Features ◽  
Molecular Pattern ◽  
Significant Difference ◽  
Cytoreductive Treatment ◽  
Wbc Count

Abstract Background. In patients with Ph-negative chronic myeloproliferative neoplasm (MPN) the molecular pattern, beside other characteristics at diagnosis, has been related to the disease prognosis. Aim. To compare clinical and biological features at diagnosis and during the follow-up in gender/age-matched MPN patients showing different molecular pattern. Material and methods. The Registro Italiano Trombocitemie (RIT) is a web-based registry that includes thrombocythemic MPN patients diagnosed according to PVSG or WHO criteria, registered after 2005, and then prospectically followed. The JAK2 V617F mutation (JAK2+) was reported in 941 (58.4%) out of 1610 tested patients. On the basis of subsequent tests, performed in part of the JAK2 WT (JAK2-) subjects, 103 patients were JAK2-/CALR+ (CALR+), 14 patients were JAK2-/CALR-/MPL+ (MPL+), and 46 were JAK2-/CALR-/MPL- (3NEG). The 103 CALR+ patients were compared with 309 (103 x 3) JAK2+ patients matched for gender, age, and revised diagnosis (WHO 2008 criteria). A similar comparison was done between 46 3NEG patients and other 138 (46 x 3) JAK2+ matched patients. Results. CALR+ and matched JAK2+ patients had, as expected, the same gender distribution (males 41%), the same median age (51 years), and no significant difference (p 0.42) in the WHO diagnosis distribution. CALR+ patients, as compared with JAK2+ patients, showed at diagnosis: higher median platelet (PLT) count (839 vs 718 x109/L, p<0.001); lower median white blood cell (WBC) count (7.3 vs 8.9 x109/L, p<0.001); lower median hemoglobin (Hb, 14.2 vs 14.8 g/dL in males, p 0.01; 12.9 vs 14.0 g/dL in females, p<0.001); lower median hematocrit (HCT, 42.4 vs 45.0 %, p 0.002 in males; 38.7 vs 42.2 in females, p<0.001); lower rate of low (<5) serum erythropoietin (0 vs 32%, p 0.003); lower rate of prior thrombosis (PrTh, 5/103, 4.9% vs 60/309, 19.4%, p<0.001), observed for both arterial and venous PrTh; lower rate of high/intermediate thrombotic risk (IPSET, 37% vs 55%, p 0.003). CARL+ and JAK2+ patients had the same rate of antiplatelet and cytoreductive treatment (96% vs 96%, and 86% vs 84%, respectively). During the follow-up the incidence of thrombotic and hemorrhagic events was not significantly different (1.3 vs 1.1/100 pt-years, and 1.0 vs 0.6/100 pt-years, respectively). Moreover, no significant difference was observed in the incidence of evolution to overt primary myelofibrosis (PMF, 0.76 vs 0.61/100 pt-years), polycythemia vera (PV, 0 vs 0.24/100 pt-years), and AL/MDS (0.08 vs 0.10/100 pt-years). Finally, the same overall survival was found after 5, 10. 15, and 20 years (99, 97, 94, 93%, respectively). 3NEG patients, as compared with JAK2+ matched patients, showed at diagnosis: lower median WBC count (7.9 vs 10.9 x 109/L, p 0.03); lower Hb and/or HCT level (p 0.006); lower rate of splenomegaly (7% vs 28%, p 0.003); lower rate of symptoms (35% vs 51%, p 0.049). No significant difference was found in: median PLT count (700 vs 720 x 109/L, p 0.61); PrTh (7% vs 16%, p 0.11); prior hemorrhage (4.7% vs 7.5%, p 0.52); high/intermediate thrombotic risk (IPSET, 36 vs 48%, p 0.37). Moreover, no significant difference was observed during the follow-up in: antiplatelet and cytoreductive treatment; thrombosis and hemorrhage rate; PMF, PV, and AL/MDS evolution; overall survival. Conclusion. CALR+ patients, as compared with JAK2+ matched patients, although showed a lower thrombotic risk (lower WBC and HCT levels, lower PrTh rate), received the same antiplatelet and cytoreductive treatment, had the same incidence of adverse events during the follow-up (vascular complications and disease evolution/transformation), and had the same overall survival. 3NEG patients, as compared with JAK2+ matched patients, showed results similar to those observed by comparing CALR+ and JAK2+ matched patients. To better define the role of the precise definition of molecular pattern in Ph-MPN patients, new prospective controlled studies seem necessary. Disclosures De Stefano: Janssen Cilag: Research Funding; Roche: Research Funding; Novartis: Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Bruno Farmaceutici: Research Funding; Celgene: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Shire: Speakers Bureau. Passamonti:Novartis: Consultancy, Honoraria, Speakers Bureau.

Cytoreductive Therapeutic Approach in the Essential Thrombocythemia (ET) Patients of the Registro Italiano Trombocitemia (RIT): Preliminary Data

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5248-5248
Author(s):  
Luigi Gugliotta ◽  
Alessia Tieghi ◽  
Anna Candoni ◽  
Monia Lunghi ◽  
Gianluca Gaidano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Essential Thrombocythemia ◽  
Therapeutic Approach ◽  
Jak2 V617f ◽  
Bone Marrow Biopsies ◽  
Thrombotic Risk ◽  
Significant Difference ◽  
Cytoreductive Treatment ◽  
Wbc Count

Abstract Background: the Registro Italiano Trombocitemia, that is a GIMEMA project, has been activated to registry Italian Essential Thrombocythemia (ET) patients, to improve the diagnosis appropriateness (WHO criteria), to verify the prognostic value of the clinical and biological parameters, to evaluate the compliance to the therapeutical Italian guidelines (1), and to create a network for activation of new studies. Objective: this analysis is mainly devoted to describe the ET patients registered in the RIT and to evaluate the therapeutic approach adopted in the 102 participating hematological centers. Material and methods: two thousand and fifteen ET patients have been registered after the written informed consent was obtained, and data validation by various expert panels is in progress. This preliminary report considers 1785 patients, diagnosed mainly (1078, 60.4%) since the publication in the year 2004 of the ET therapy Italian guidelines (1). Results: the patients, 678 (38%) males and 1107 (62%) females, showed at diagnosis: age 60.3 ± 16.8 years with higher values in males than in females (61.7 ± 15.3 vs. 59.4 ± 17.7, p&lt;0.05), being the patients below 40 years 14% and those over 70 years 33% of cases; PLT count (109/L) 846 ± 309 with lower values in males than in females (813 ± 261 vs. 866 ± 334, p&lt;0.002), and with values 1001–1500 and over 1500 in 16% and 4% of cases, respectively; WBC count (109/L) 9.1 ± 2.9, without difference by sex, and with values 12–15 in 10% and over 15 in 3% of cases; Hgb (g/dL) 14.2 ± 1.6 with higher values in males than in females (14.8 ± 1.5 vs. 13.8 ± 1.5, p&lt;0.001), and with values over 16.5 in 8.5% of males and 2.7% of females, respectively; splenomegaly in 488 (27%), echo-documented in 324 cases (18%); history of hemorrhage and thrombosis in 90 (5%) and 325 (19%) of cases, respectively; disease-related symptoms in 41% and general thrombotic risk factors in 93% of cases, respectively. The WHO 2001 diagnostic criteria were reported for 33% of cases observed before the year 2004 and for 53 % of cases observed since the year 2004. Detailed data at diagnosis were reported as follows: bone marrow biopsy in 1087 cases (61%) with a frequency of 51% and 68% before and since the year 2004, respectively; bcr-abl study in 1045 cases (59%); cytogenetics in 828 cases (46%) with karyotype abnormalities in 27 patients (3%). The JAK2 V617F mutation, searched in 574 cases (32%), was observed in 320 of them (56%). The patient follow-up was 4.5 ± 4.5 years with a total of 5245 pt-yrs. During the follow-up the hemorrhagic events were 5.7% (1.3/100 pt-yrs), being the major events 1.9% (0.4/100 pt-yrs); the thrombotic complications were 14.9 % (3.3/100 pt-yrs), resulting the major arterial 9.4% (2.1/100 pt-yrs), the major venous 3.5% (0.8/100 pt-yrs) and the minor thrombosis 2% (0.4/100 pt-yrs). An antiplatelet treatment, almost always with low dose aspirin, was performed in 75% of the patients, without significant difference in the cases diagnosed before and since the 2004. A cytoreductive treatment was done with use of Hydroxyurea (HU, 64%), Interferon alpha (IFN, 16%), Anagrelide (ANA, 15%), Busulfan (BUS, 4%), and Pipobroman (PIPO, 2 %). In the ET patients diagnosed since the year 2004 respect those diagnosed before, it was observed a decrease in the use of all the cytoreductive drugs, particularly BUS (−62%), IFN ((−62%), and ANA ((−68%). The use of the cytoreductive drugs was related to the patient mean age (years): BUS (76), PIPO (72), HU (67), ANA (53), IFN (48). In the patients diagnosed since the 2004 as compared with those before 2004, the mean age of the treated patients increased for BUS (from 69 to 81 yrs, p&lt;0.001) and for HU (from 64 to 69 yrs, p&lt;0.001) while it decreased for IFN (from 49 to 46 yrs, p&lt;0.05). Conclusion: in the analyzed patients of the ET Italian registry the diagnosis appropriateness resulted improved in the cases observed since the year 2004 respect those observed before, with an increase of bone marrow biopsies from 51% to 68% of patients. Moreover, in accord with the ET therapy Italian guidelines, the use of the cytoreductive drugs was less frequent in the patients diagnosed since the year 2004 than before (particularly for BUS, IFN, and ANA) and the more safe molecules IFN and ANA were preferentially deserved to the younger patients.

scholarly journals Patients with Unexplained Thrombosis Require a Prompt Investigation to Search a Chronic Myeloproliferative Neoplasm (MPN), Even If Platelet Count Is <600x109/L. Analysis on 129 Patients from Registro Italiano Trombocitemie (RIT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5181-5181
Author(s):  
Giulia Benevolo ◽  
Alessandra Iurlo ◽  
Gabriele Gugliotta ◽  
Alessia Tieghi ◽  
Gianluca Gaidano ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Advisory Committees ◽  
Thrombotic Risk ◽  
Cytoreductive Treatment ◽  
Wbc Count

Abstract Background In patients with Ph-negative MPN, a prior thrombosis (PrTh) occurs in around 1/5 of cases, with variable platelet (PLT) count and variable distance from diagnosis. Objective To investigate the influence of PLT count at PrTh on diagnostic and therapeutic approach in MPN patients. Material and methods We evaluated 129 MPN patients from RIT, reclassified according to WHO 2008 criteria as ET (n70), initial-primary myelofibrosis (n29), early-PV (n10), and unclassifiable-MPN (n20). Results Patients, 60 males and 69 females, showed following PrTh: 91(71%) major arterial (37 AMI, 4 angina, 24 stroke, and 26 TIA); 12(9%) minor arterial; 22(17%) major venous (8 DVT, 7 splanchnic, 4 cerebral sinus, 3 pulmonary embolism); and 4(3%) minor venous events. PrTh occurred at a median distance of 4.1 months (range 0.1-118) from MPN diagnosis. This distance was >24 months in 21(16%) patients. At occurrence of PrTh, median age was 58 years. PLT count (x109/L) had a median value of 661 (range 150-2200), and was ≤450, 451-600, 601-700, 701-1000, and >1000 in 15(12%), 35(27%), 26(20%), 43(33%), and 10(8%) patients, respectively. Median white blood cell (WBC) count was 9.0 x 109/L and median hematocrit (HCT) value was 46% in males, and 41% in females. Median time (months) from PrTh to diagnosis of MPN was higher (p0.004) in patients with lower PLT count (x 109/L): ≤450 (50.2), 451-600 (11.7), 601-700 (2.7), 701-1000 (1.8), and >1000 (1.4). After occurrence of PrTh, all patients received conventional anti-thrombotic treatment, but in 7(5.4%) patients 9 recurrent thrombosis were reported before MPN diagnosis (11/100 pt-years). At MPN diagnosis, clonality was documented in 101(78%) patients (JAK2 V617F mutation in 96 cases, 74%). The age was >60 years in 61(47%) patients. PLT count (x109/L) had a median value of 720 (166-2440), and was ≤450 (n 7, 5%), 451-600 (n 21, 16%), 601-700 (n 28, 22%), 701-1000 (n 58, 45%), >1000 (n15, 12%). WBC count (109/L) had a median value of 8.9, and was >10 in 40 (31%) cases. Median HCT level (%) was 45.6 in males and 42.1 in females. Cardiovascular risk factors (CVRF), comorbidities and symptoms were documented in 103(80%), 97(75%), and 57(44%) cases, respectively. Thrombotic risk (IPSET-Th) was high in 97.5%, and intermediate in 2.5% of cases. All 129 patients received anti-thrombotic drugs (low dose aspirin in 95% of cases) and, immediately after the diagnosis, they started a cytoreductive treatment (hydroxycarbamide 89%, anagrelide 8%, interferon-alpha 3%). Patients with a PLT count (x109/L) at PrTh ≤600(n 50), as compared with those with a PLT count >600(n 79), showed a longer median time to the MPN diagnosis (16.7 vs 2.0 months, p<0.001). No significant difference was found in the rate of: arterial PrTh (80% vs 79.7%, p0.97); recurrence of thrombosis before the diagnosis (8% vs 4%, p0.69); JAK2 V617F mutation (80% vs 71%, p0.29); age >60 years (52% vs 44%, p0.39); CVRF (82%vs79%, p0.63); WBC >10 x109/L (23% vs 39%, p0.07); HCT high level [>47% in males, >44% in females](28% vs 36%, p0.37), and high thrombotic risk [IPSET-Th] (96%vs99%, p0.56). During follow-up (median 7.9 years) they showed a higher incidence of thrombosis recurrence (30%vs15%, p0.04; 4.5 vs 1.7/100 pt-y, p<0.01) Conclusion Time to MPN diagnosis was significantly longer in patients with PLT count (x109/L) at PrTh ≤600 vs >600, and this time to diagnosis was characterized by a not negligible thrombosis recurrence. Moreover, during follow-up they showed a higher incidence of thrombosis recurrence. This analysis strongly suggests that a PLT count <600 or even <450 x109/L, in patients with unexplained thrombosis, deserves the search of a probable MPN, in order to promptly start cytoreductive treatment in addition to a conventional anti-thrombotic therapy. Disclosures Passamonti: Novartis: Consultancy, Honoraria, Speakers Bureau. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees.

Response to Frontline Therapy with Second Generation Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: Analysis of Outcome for b3a2 Vs. b2a2 Fusion Transcripts

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3781-3781 ◽  
Author(s):  
Carlos G. Romo ◽  
Hagop M Kantarjian ◽  
Rajyalakshmi Luthra ◽  
Alfonso Quintás-Cardama ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Research Funding ◽  
Initial Therapy ◽  
Molecular Response ◽  
Exon 2 ◽  
Free Survival ◽  
Significant Difference ◽  
Frontline Therapy

Abstract Abstract 3781 Background: CML is characterized by the reciprocal translocation between chromosomes 9 and 22 [t(9;22)(q34;q11.2)], also known as the Philadelphia chromosome. This results in the formation of the BCR-ABL fusion gene, which is translated to a protein with increased tyrosine kinase activity. The breakpoint in the BCR gene can occur in different sites, most commonly between exons 13 and 15 which fuse to exon 2 of the ABL gene creating the b2a2 and b3a2 junctions. Previous studies have reported a better outcome for patients (pts) having a b2a2 transcript when treated with imatinib. To our knowledge there are no published reports analyzing the outcome of pts treated with a 2ndgeneration TKI as initial therapy for CML according to the fusion transcript. We analyzed the significance of these variations among pts with CML in chronic phase (CP) enrolled in 2 parallel trials of dasatinib and nilotinib as initial therapy. Patients and Methods: A total of 204 pts with CML in CP, treated at our institution between 2005 and 2012 with nilotinib or dasatinib as frontline therapy were included in this analysis. Among them 88 (43%) had the b2a2 transcript (median age of 47 years; range 18–80) at the start of therapy, 74 (36%) showed the b3a2 variant (median age of 47; range 17–82 years), and 42 (21%) presented both (median age 53; range 27–81). One patient had a b3a3 transcript and 2 pts showed an e1a2 transcript. Forty-two (48%) of those with b2a2 were treated with dasatinib and 46 (52%) with nilotinib; of the pts with b3a2 34 (46%) were treated with dasatinib and 40 (54%) with nilotinib, in the group of pts with both transcripts 24 (57%) received dasatinib 24, and 18 (43%) of them nilotinib (Table 1). Results: The Sokal risk group for those with the b2a2 transcript was high in 10%, intermediate in 29%, and low in 61%. For pts with b3a2 the risk classification was 5%, 25, and 70%, respectively. The group with both transcripts had 10%, 31% and 69%, respectively. Significant difference was observed in the time of molecular response and overall outcome between pts with b2a2 and those with b3a2 (CCyR 91% vs. 96%; MMR 75% vs. 91%, respectively). The 3-year probability of overall survival (OS) was 100% for both groups. The 3-year probability of event-free survival (EFS) was 93% and 99%, and the transformation-free survival (TFS) 99% and 98% for the b2a2 and the b3a2 group respectively (Table 2). On the 12 mo. follow-up one of the pts with e1a2 transcript achieved CCyR (treated with nilotinib), and the second patient (pt) major cytogenetic response (receiving dasatinib). The pt presenting with b3a3 was treated with dasatinib and achieved MMR by 3 mo. and CCyR at the 12 months follow-up. Conclusions: Although all pts whether they express b3a2 or b2a2 at diagnosis, have an excellent overall survival, those with b3a2 have a significantly higher rate of molecular responses and a trend for better EFS. These results mirror what we have previously reported for pts treated with imatinib as initial therapy. The biologic characteristics for this difference warrant further investigation. Disclosures: Kantarjian: Novartis: Research Funding; Bristol Myers Squibb: Research Funding; Ariad: Research Funding; Pfizer: Research Funding. Jabbour:Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Cortes:Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.

scholarly journals Improved Survival of Patients with Myelofibrosis in the Last Decade

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 50-51
Author(s):  
Lucia Masarova ◽  
Prithviraj Bose ◽  
Naveen Pemmaraju ◽  
Lingsha Zhou ◽  
Sherry A. Pierce ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Myeloproliferative Neoplasm ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Grant Support ◽  
Before And After

Introduction: The myeloproliferative neoplasm myelofibrosis (MF) is associated with reduced overall survival (OS) compared to the general population. In 2011, the JAK1/2 inhibitor ruxolitinib, was approved in the USA for the treatment of intermediate and high-risk MF. Long-term follow-up of patients in pivotal phase 3 studies showed survival benefit of ruxolitinib therapy. Objective: We sought to evaluate the outcome of patients with MF diagnosed before and after the year of 2010 to assess whether OS changed in the past decade in the era of ruxolitinib. Methods: We retrospectively reviewed the charts of 1346 patients with MF who presented to our institution in the last 25 years and compared clinical parameters and outcomes between those presented before and after the year of 2010 (before / after y. 2010). Newly diagnosed MF patients and patients within 12 months from diagnosis who were previously only treated with supportive therapy (danazol, growth-factors, steroids) were included. Cytogenetics (≥10 metaphases) was classified according to Gangat, JCO, 2011. Molecular analysis (≥ 28 genes) was performed only after y. 2010 by using next generation sequencing platform. Fisher exact test and χ2 were used for analysis of categorical variables. Overall survival (OS) was estimated using the Kaplan-Meier method and comparison was done by the log-rank test. Results: Among the 1346 patients, 806 (60%) patients were seen after y. 2010. Median age of all patients was 65 years (range, 20-94), 62% were males. Patient characteristics with comparison between groups are shown in Table 1. Patients after y. 2010 were older, with lower WBC and lower lactate dehydrogenase, but had more symptoms. The distribution of IPSS scores between groups were comparable at around 10% for low, 36% for intermediate-1, 20-25% for intermediate-2 and ~30% for high risk. Eighty-five and 80% of patients before and after y. 2010, respectively, received therapy for MF at our institution. Overall, 78 patients (37 after y. 2010) underwent stem cell transplantation. Among treated patients at our institution, 25% (n 117) and 37% (n 241) before and after y. 2010 received ruxolitinib during their follow-up. Ruxolitinib therapy was initiated with a median time of 2 months (range, 0.2-156) from presentation to our institution, longer in those before y. 2010 (11 vs 1 months in patients after y. 2010, respectively, p = 0.001) After a median follow-up of 30.4 months (range, 0.9-266); 659 (49%) of patients died. More deaths were noticed in those before y. 2010 (74% vs 32 %, respectively, p &lt; 0.001); but these patients had also longer follow-up (37.5 months vs 25 months, p &lt; 0.001). Eighty-five patients (10%) developed acute leukemia: 2 cases per 100 person-years per observation for both groups. Patients after y. 2010 had superior OS to those before y. 2010 with HR 0.7 (95% CI: 0.59-0.82), p &lt; 0.001, Figure 1. Superior OS was observed in all patients after y. 2010 (vs before y. 2010) when stratified by IPSS score (higher equals for combination of int -2 and high, Figure 2), or age (cutoff of 65 years, Figure 3). Patients exposed to ruxolitinib had superior OS regardless of being diagnosed before or after y. 2010, with respective medians of 98 (95% CI: 78-118) and 91 (95% CI: 73-109) months (details to be presented at the conference). Conclusion: Our results demonstrate that survival of patients with MF has improved in the last decade. Survival has improved in younger and older patients as well as in those with more advanced disease (per IPSS risks). Many factors may have contributed to the observed improvement in outcome of MF patients, including new therapies, e.g. ruxolitinib, as well as improved supportive management and disease awareness. Disclosures Bose: Blueprint Medicines Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Kartos Therapeutics: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; NS Pharma: Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; CTI BioPharma: Honoraria, Research Funding; Promedior, Inc.: Research Funding. Pemmaraju:Daiichi Sankyo: Research Funding; DAVA Oncology: Honoraria; Blueprint Medicines: Honoraria; Roche Diagnostics: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Honoraria; Incyte Corporation: Honoraria; MustangBio: Honoraria; Plexxikon: Research Funding; Samus Therapeutics: Research Funding; SagerStrong Foundation: Other: Grant Support; Novartis: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; LFB Biotechnologies: Honoraria; Stemline Therapeutics: Honoraria, Research Funding; Cellectis: Research Funding. Kantarjian:Novartis: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; Astex: Research Funding; Takeda: Honoraria; Agios: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding. Verstovsek:CTI Biopharma Corp: Research Funding; Protagonist Therapeutics: Research Funding; PharmaEssentia: Research Funding; ItalPharma: Research Funding; Gilead: Research Funding; Promedior: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Genentech: Research Funding; AstraZeneca: Research Funding.

scholarly journals Azacitidin Is Effective in the Therapy Related Myelodysplastic Syndrome.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5554-5554
Author(s):  
Hirofumi Yamauchi ◽  
Masahiro Yokoyama ◽  
Yuko Mishima ◽  
Noriko Nishimura ◽  
Kyoko Ueda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Research Funding ◽  
Poor Prognosis ◽  
De Novo ◽  
Genetic Alterations ◽  
Poor Risk ◽  
Significant Difference ◽  
One Year

Abstract Introduction: Myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms characterized by abnormal maturation of precursor cells which often translates into peripheral blood cytopenias and a high rate of transformation to acute myeloid leukemia (AML) due to accumulation of genetic alterations. The AZA-001 trial showed azacitidine (AZA) significantly prolonged median overall survival compared with conventional care regimens (24.5 vs 15.0 months; P=0.0001). AZA is standard first-line treatment for Intermediate-2 and High-risk myelodysplastic syndrome patients who are not immediate candidates for allogeneic stem cell transplantation, but this study included no cases of therapy related MDS (t-MDS). T-MDS is known to have poor prognosis, therefore it is very important to analyze the outcome of patients with t-MDS treated in the front-line with AZA. Methods: We studied newly diagnosed 29 MDS patients who were treated by AZA in our hospital from July, 2010 to April, 2016, retrospectively. AZA was given subcutaneously at 75 mg/㎡per day for 5 or 7 days every 28 days. Results: We analyzed 29 MDS patients. According to the WHO classification, there were 12 RA, 15 RCMD, 10 RAEB-1, 2 RAEB 2 and 1 MDS-U. The median age was 70 year (range 49-88), and men was 12 (41.3%). There were 12 de novoMDS cases (41.3%) and 17 t-MDS cases (58.6%). All of the t-MDS patients had previously received chemotherapy (17 patients, 100%) and 9 patients had also received radiotherapy (9 patients, 53%). Very poor risk group was 47.1% (9/17) in t-MDS group compared to 25.0% (3/12) in de novo MDS group (P=0.26). Median follow up time was 11.4 months (range 1.4-47.8). Twenty five patients (86.3%) were treated by AZA for 5 days. Four patients (13.7%) were treated by AZA for 7 days, but all 4 patients decreased the dosing period to 5 days due to unacceptable toxicity. AZA was given for a median of 4 cycles (range 1-33). In 29 MDS patients, 1-year overall survival (OS) was 60.5% (95% CI, 38.7-76.7%) and 1-year PFS was 40.1% (95% CI, 18.8-60.6%). After a median follow-up of 11.4 months, median OS was 18.7 months (95% CI, 9.4-21). One-year OS was 59.3% in t-MDS group compared to 63.6% in de novo MDS group (P=0.294). 1-year PFS was 38.4% in t-MDS group compared to 40.4% in de novo MDS group (P=0.626). One-year OS was 37.5% in very poor risk karyotype group (R-IPSS) compared to 74.6% in not very poor risk karyotype group (P=0.000748). 1-year PFS was 43.2% in very poor risk karyotype group compared to 39.0% in not very poor risk karyotype group (P=0.594). Focusing on t-MDS group, 1-year OS was 46.9% in very poor risk karyotype group (8/17 47%) compared to 74.1% in not very poor risk karyotype group (9/17 53%) (P=0.054). 1-year PFS was 48.0% in very poor risk karyotype group compared to 26.0% in not very poor risk karyotype group (P=0.339). Conclusions: In our study, 1-year OS in all MDS patients was 60.5%. It was slightly poor prognosis than 1-year OS in AZA-001 trial (about 70%). Our study include t-MDS cases (58.6%). Additionally, AZA was given for a median of 4 cycles in our study but 6 cycles in the AZA-001 trial. It showed severe patient's background of our study. These difference may cause the lower median OS and poorer prognosis. There trended to be more patients who had very poor risk karyotype in t-MDS group, but there was no significant difference between t-MDS and de novoMDS for the 1-year OS and PFS. Azacitidin is effective in the therapy related myelodysplastic syndrome. Disclosures Yokoyama: Chugai: Consultancy. Mishima:Chugai: Consultancy. Nishimura:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Kyowa Kirin: Honoraria, Research Funding; Chugai: Research Funding; Otsuka: Consultancy; Meiji-Seika: Consultancy.

Molecular and Clinical Features of the Myeloproliferative Neoplasm Associated with JAK2 Exon 12 Mutations: a European Multicenter Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3904-3904 ◽  
Author(s):  
Francesco Passamonti ◽  
Susanne Schnittger ◽  
François Girodon ◽  
Jean-Jacques Kiladjian ◽  
Mary Frances McMullin ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Clinical Features ◽  
Conflicts Of Interest ◽  
Collaborative Study ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Female Ratio ◽  
Significant Difference ◽  
Wbc Count

Abstract Abstract 3904 Poster Board III-840 While about 95% of patients with polycythemia vera carry the unique V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the minority of JAK2 (V617F)-negative subjects. The initial study [N Engl J Med 2007 Feb 1;356(5):459-68] led to the conclusion that JAK2 exon 12 mutations define a distinctive myeloproliferative syndrome that affects patients who currently receive a diagnosis of polycythemia vera or idiopathic erythrocytosis. Very recent studies suggest that the 'GGCC' haplotype of JAK2 confers susceptibility to the somatic acquisition of both JAK2 (V617F) and exon 12 mutations [Nat Genet 2009 Apr;41(4):450-4, Leukemia 2009 May 14, Epub ahead of print]. Indeed, we reported pedigrees with familial polycythemia vera in which there were both JAK2 (V617F)-positive and JAK2 exon 12 mutation-positive siblings [Blood 2008 Feb 1;111(3):1686-9]. The myeloproliferative neoplasm associated with JAK2 exon 12 mutations is a rare disorder, and only small groups of patients have been reported so far by various investigators. We therefore started a collaborative study in Europe with the aim of collecting about 100 patients with this condition in order to define the molecular and clinical features of this myeloproliferative neoplasm. An ad hoc database was developed for data collection and management. As of August 1, 2009, 77 patients with the required clinical and hematologic data at diagnosis have been recruited (median follow-up 3.2 years, range 0-27 years), while complete follow-up information was available for 57 of these patients. Various approaches were employed for the detection of JAK2 exon 12 mutations, including genomic DNA sequencing, allele-specific PCR assays, and high resolution melting. Overall, 16 different exon 12 mutations were identified. The most frequent mutation were N542-E543del (26 patients), K539L (12 patients), R541-E543delinsK (6 patients), and F537-K539delinsL (6 patients); the remaining mutations occurred less frequently. With respect to the clinical phenotype at presentation, the Kruskal-Wallis test did not reveal any significant difference between the above most frequent mutations. Median age at diagnosis was 53 years (range 15-92), and the male/female ratio was 43/34. Mean hemoglobin level was 19.3 ± 2.2 g/dL, mean WBC count 8.5 ± 3.2 × 109/L, and mean PLT count 334 ± 197 × 109/L. Overall, 48 out of 77 (62%) patients presented with isolated erythrocytosis, 12 (16%) with erythrocytosis and leukocytosis (WBC count > 10 × 109/L), 8 (10%) with erythrocytosis and thrombocytosis (PLT count > 400 × 109/L), and 8 (10%) displayed a full myeloproliferative pattern (erythrocytosis, leukocytosis and thrombocytosis). Serum erythropoietin level was below the lower normal limit in 46 out of 58 (79%) patients. Twenty-one of 25 (84%) patients had endogenous erythroid colonies. During follow-up, two patients had deep venous thrombosis, two progressed to post-polycythemia vera myelofibrosis (diagnosed according to the IWG-MRT criteria) and two developed a myelodysplastic syndrome. In conclusion, the available data indicate that the myeloproliferative neoplasm associated with JAK2 exon 12 mutations is mainly associated with isolated erythrocytosis at clinical onset, but also suggest that the subsequent clinical course may be similar to that of JAK2 (V617F)-positive polycythemia vera, at least in a portion of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Interferon in Polycythemia Vera (PV) Yields Improved Myelofibrosis-Free and Overall Survival

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2942-2942
Author(s):  
Ghaith Abu Zeinah ◽  
Spencer Krichevsky ◽  
Diana Jaber ◽  
Niamh Savage ◽  
Claudia Sosner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Research Funding ◽  
Advisory Board ◽  
Age At Diagnosis ◽  
Entire Group ◽  
Early Use ◽  
Cytoreductive Treatment ◽  
Treatment Analysis

Introduction: The progression of polycythemia vera (PV) to myelofibrosis (MF) is associated with significant morbidity and mortality. Interferon alfa (rIFNa), a disease-modifying agent, has potential to delay or prevent post-PV MF and improve overall survival but supporting data are required. We present results of the largest study demonstrating improved myelofibrosis-free and overall survival (MFS and OS) of rIFNa treated PV patients (pts) compared to other PV pts. Objectives: To estimate the MFS and OS of treated PV pts and determine the relative risk for post-PV MF and mortality of those treated with rIFNa compared to those treated with other standard therapy. Methods and Study Design: To ensure sufficient follow-up for analysis of long-term outcomes, this IRB approved study identified all adult pts treated at our center from 1974-2019 according to PVSG criteria (1974-2007), our published criteria (2008-2016) and WHO criteria (2016-2019) using a standardized query of electronic medical records. Demographic data, clinical characteristics, treatment history and outcomes were collected. The extended follow-up of this large PV cohort permitted us to evaluate the effectiveness of PV therapy using both intention-to-treat (ITT) and treatment duration (on-treatment) analyses. In the ITT analysis, pts were assigned to rIFNa or hydroxyurea (HU) arms according to the first cytoreductive treatment they received for at least one year or to phlebotomy only (PHL-O) if no cytoreductive treatment was given. On-treatment analysis was performed to account for cross-over and assess how duration of a given therapy influenced outcomes. The onset of post-PV MF was defined by IWG-MRT criteria. MFS and OS were estimated using Kaplan-Meier methods and the log-rank test compared survival between treatment arms in ITT analysis. Multivariate analysis of post-PV MF risk and mortality was performed using a Cox proportional hazards model. The model accounts for age at diagnosis and is stratified by treatment arms (ITT) or by treatment as a time-dependent covariate (on-treatment). Results: We identified 306 PV pts whose median age at diagnosis was 54 years (yr) (range 20-91) and of whom 151 (49%) were women. The median follow-up was 11 yr (range 1-45). The first line treatment was rIFNa in 75 (25%), HU in 134 (44%) or other cytoreductive regimens in 37 (12%). PHL-O was instituted in 60 pts (20%). Treatment cross-over occurred in 82 pts (27%), with the least from rIFNa arm (22%) (Table2). Treatment arms differed by age at diagnosis with a median of 50, 59 and 52 years for rIFNa, HU and PHL-O (p <0.01) (Table 3). The median MFS and OS was 19.5 and 26.3 yr for the entire group; 27 and 28 yr for rIFNa arm; 18 and 26 yr for HU arm; and 14 and 25 yr for PHL-O (log-rank p<0.01 for MFS and p=0.01 for OS) (Figure 1). In multivariate analysis that included age, rIFNa arm had a lower risk of post-PV MF or death compared to HU arm (HR 0.43, p=0.03 and HR 0.44, p=0.04 respectively) and to PHL-O arm (HR 0.22, p<0.01 and HR 0.35, p=0.03 respectively) (Figure 2). The PHL-O arm had a higher risk of post-PV MF compared to HU as well. Older age at diagnosis was a risk factor for post-PV MF and death. Accounting for cross-over, 138 pts received rIFNa at any time for a cumulative of 980 patient-years (median: 5.3, range 1-25 yr). On-treatment analysis associated rIFNa with an 8% and 7% relative risk reduction of post-PV MF and all-cause mortality respectively (age-adjusted HR of 0.92, p<0.01 and 0.93, p=0.01). Discussion: This is the largest study with the longest follow-up of rIFNa treated PV pts and the first to demonstrate that rIFNa yields superior MFS and OS compared to HU or PHL-O. This study addresses the critical issue that randomized controlled trials to date failed to answer owing to limited follow-up duration and lack of surrogate endpoints for survival. Although the median age of the entire group is younger than the reported median age at PV diagnosis, multivariate analysis showed that both the survival benefit of rIFNa and the reduced risk of fibrosis are independent of age. This study supports early use of rIFNa for PV, especially in younger patients who should not be deprived of a disease-modifying therapy for being "low risk" by consensus criteria. Conclusions: rIFNa yields improved MFS and OS of PV patients, independent of age, in this large study with extended follow up. Early use of rIFNa should be considered routinely in the management of PV. Disclosures Ritchie: agios: Other: Advisory board; Tolero: Other: Advisory board; Genentech: Other: Advisory board; Celgene, Incyte, Novartis, Pfizer: Consultancy; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Celgene: Other: Advisory board; Pfizer: Other: Advisory board, travel support. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Interim or End of Treatment FGD-PET Complete Response Does Not Have Adequate Predictive Value in Mature T/NK Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1813-1813
Author(s):  
Tatyana Feldman ◽  
Larysa Sanchez ◽  
Patrick Toth ◽  
David Panush ◽  
Lori A Leslie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Predictive Value ◽  
Research Funding ◽  
Nk Cell ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Significant Difference

Abstract Introduction: Cure rate of Mature T/NK cell lymphoma (TCL) is rather low and multiple trials are being conducted to improve frontline therapy outcomes. Consolidation with autologous stem cell transplant is becoming widely used as a mean of improving survival (SCT). Based on data from several retrospective trials, pts who achieve CR may not benefit from consolidative SCT. There is no data available on the role of PET-CR as defined by using Deauville criteria (which became standard in response assessment of NHL (The Lugano Classification 2014)). We performed retrospective analysis of 59 pts with TCL examining the correlation between PFS/OS and iPET and eotPET. Methods: 59 pts newly diagnosed pts with TCL treated between 2008-2016 for whom interim and eotPET scan were available. It was our routine practice to obtain baseline, interim (after 3 cycles of chemotherapy) and eotPET. Pathology slides of outside cases were centrally evaluated by a hematopathologist to confirm diagnosis. Baseline, interim and eotPET were centrally reviewed by a nuclear medicine radiologist blinded to clinical outcomes who assigned Deauville score (DS) to every PET. Responses were recorded according to the Lugano classification 2014. Descriptive statistics and Kaplan Meier method was used to calculate the Progression-free survival (PFS) and Overall survival (OS), two-sided Log-rank test was used to compare OS and PFS between PET groups. Results: Detailed demographic is presented in Table1. Median age at diagnosis is 59, sixty two percent males, 37% female; ALCL 34%, PTCLnos 22%, AITL 19%, and ATLL 10%; most of pts were advanced stage. Most common chemotherapy regimens used were CHOP/CHOEP, HCVAD, and CODOX, SMILE. Median follow up time for the entire cohort was 22.7mo. Forty nine percent of pts progressed and 29% of pts died during follow up. Cause of death for majority of pts was disease progression. Following Deauville scores were assigned on iPET and eotPET respectively: DS1 in 37% and 39%, DS2 in 30% and 35%, DS3 in 15% and 6%, DS4 in 9% and 4%, DS5 in 9% and 16%. We analyzed mPFS and mOS for PET-CR using DS1-2 or DS1-3 to define it. Sixty seven percent and 82% were considered in PET-CR on iPET based on DS 1-2 and DS 1-3 respectively. PET-CR went up to 77% and 83% respectively on eotPET. For final analysis, DS1-2 was used to define PET-CR as no statistically significant difference in mPFS and mOS was noted between DS1-2 and DS1-3. With median follow up of 22.7mo, two-year mPFS and mOS for the cohort were 50% and 74% respectively. Two- year mPFS for iPET-CR and eotPET-CR were 62%. Two-year mOS for iPET-CR and eotPET-CR were 86%% and 83%. Two-year mPFS for iPET-PR and eotPET-PR were 37% and 67%. Two-year mOS for iPET-PR and eotPET-PR were 70% and 100 % (not statistically significant difference with PET-CR mPFS and mOS). None of the pts with PD on iPET were alive at two year. Two-year mOS for eotPET-SD and eotPET-PD are 40%. Negative predictive value of iPET and eotPET is 61%, positive predictive value is 65% and 72% respectively. Conclusion: While PET-SD and PD is quite predictive of poor survivorship, significant number of PET-CR pts will relapse. Even though PET-CR rate to frontline therapy is high, it does not translate into durable responses for significant number of pts with TCL. Thus, PET-CR is not a sensitive enough measure to be considered as a predictor of long-term remission in TCL. It is important to develop response assessment tools which will correlate better with long term survivorship of TCL patients. Figure 1 Overall survival stratified on PET response Figure 1. Overall survival stratified on PET response Figure 2 Progression free survival stratified on PET response Figure 2. Progression free survival stratified on PET response Disclosures Feldman: Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau. Skarbnik:Pharmacyclics: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Mato:Theradex: Research Funding; TG Therapeutics: Research Funding; ProNAi: Research Funding; Gilead Sciences: Research Funding; Acerta Pharma: Research Funding; Abbvie: Research Funding; TG Therapeutics: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Abbvie: Consultancy. Chow:Seattle Genetics: Speakers Bureau. Protomastro:COTA: Employment. Leslie:Celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau. Goy:Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Writing support, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Relapsed Lenalidomide Refractory Myeloma: Long Term Follow up and Comparison of 2 Mg Vs 4 Mg Doses

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4780-4780
Author(s):  
Martha Q. Lacy ◽  
Betsy R. LaPlant ◽  
Kristina M Laumann ◽  
Shaji Kumar ◽  
Morie A Gertz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Cell Transplant ◽  
Survival Curves ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Grade 3 ◽  
Dose Levels

Abstract Background: Pomalidomide has demonstrated excellent activity in patients with relapsed, lenalidomide refractory, multiple myeloma (MM). Between November 2007 and March 2012, we enrolled 285 patients with relapsed MM on 5 sequential phase 2 trials; patients received pomalidomide at 2mg or 4 mg daily with weekly dexamethasone (Pom/dex). The approved dose of pomalidomide is 4 mg for 21 of 28 days. We wished to compare efficacy, tolerability and long-term outcomes between cohorts treated with 2 mg or 4mg daily continuously and 4mg daily for 21/28 days. Methods: After excluding two ineligible patients, 283 patients with lenalidomide refractory, relapsed MM from 5 sequential cohorts were analyzed. These patients were divided into 3 groups: Group1 received Pom 2mg for 28/28 day cycle (N= 69), Group 2 received Pom 4 mg for 28/28 day cycle (N= 95) and Group 3 received Pom 4mg for 21/28 day cycle (N= 119). All patients received oral dexamethasone given 40 mg daily on days 1, 8, 15, and 22. Response was assessed by the IMWG Uniform Response criteria. All patients received aspirin 325 mg daily for DVT prophylaxis or full dose anticoagulation. Results: The median age was 63 years (32-85); 35% were female. The median time from diagnosis was 53 months and the median number of prior regimens was 4. 127 (46%) had high-risk molecular markers. Prior therapies (% received) included lenalidomide (100%), thalidomide (46%), bortezomib (78%), autologous stem cell transplant (71%), and allogeneic transplant (4%). The median follow-up is 16.4 months (3.2-64.4). Forty eight percent are alive and 26% remain progression free; 15 patients are continuing to receive treatment. Frequency of AEs by groups are shown in Table 1. The most notable difference is grade 3+ neutropenia seen in 39% of group 1 and 56% and 57% of groups 2 and 3. Confirmed responses of PR or better were seen in 29% (group1), 35% (group2) and 24% (group3). Median duration of response (DOR) was 14.1 months (group1), 14.5 months (group2) and 10.2 months (group3). Median PFS was 5.5 months (group1), 6.9 months (group2) and 4.3 months (group3). Although the dose level cohorts were sequential rather than randomized, we compared OS between the dose levels in an exploratory manner. There was no significant difference in OS between dose levels (p=0.26). Median overall survival (OS) was 16.6 months (group1), 21.9 months (group2) and 16.0 months (group3). Conclusions: Pom/dex is active and well tolerated even in heavily pretreated patients Responses are durable. Response rates and overall toxicity are similar between the 2 mg and 4 mg doses. Neutropenia is more common in those receiving doses of 4mg daily or for 21/28 days compared to those receiving 2 mg daily. Table 1. All Grades Grade 3+ 2mg 28 Day 4mg 28 Day 4mg 21 Day 2mg 28 Day 4mg 28 Day 4mg 21 Day Anemia 68% 58% 74% 14% 15% 27% Lymphopenia 22% 51% 11% 16% 32% 8% Neutropenia 71% 82% 77% 39% 57% 56% Thrombocytopenia 51% 61% 63% 10% 9% 23% Leukopenia 59% 77% 72% 26% 38% 39% Pneumonia 7% 11% 12% 6% 7% 11% Fatigue 51% 65% 60% 9% 5% 8% Neuropathy 28% 32% 28% 0% 3% 0% Elevated Blood Glucose 10% 21% 8% 4% 6% 3% Pneumonitis 3% 2% 3% 3% 1% 1% VTE (Thrombosis) 3% 3% 3% 1% 3% 3% Secondary Malignancy 0% 2% 1% 0% 2% 1% Figure1. Kaplan Meier Overall Survival Curves Figure1. Kaplan Meier Overall Survival Curves Disclosures Lacy: Celgene: Research Funding. Fonseca:Medtronic, Otsuka, Celgene, Genzyme, BMS, Lilly, Onyx, Binding Site, Millennium, AMGEN: Consultancy, patent for the prognostication of MM based on genetic categorization of the disease. He also has sponsored research from Cylene and Onyx Other, Research Funding. Bergsagel:Novartis: Research Funding; Constellation Pharmaceutical: Research Funding; OncoEthix: Research Funding; MundiPharma: Research Funding. Stewart:Novartis: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Array BioPharma: Consultancy; Sanofi: Consultancy; Takeda Pharmaceuticals International Co.: Research Funding. Reeder:Millennium, Celgene, Novartis: Research Funding. Mikhael:Onyx: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Novartis: Research Funding.

Evaluating the Incidence of Cardiovascular and Thrombotic Events in Secondary Polycythemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3511-3511
Author(s):  
Clara Mao ◽  
Adam J Olszewski ◽  
Pamela C Egan ◽  
Peter Barth ◽  
John L Reagan
Keyword(s):  
Research Funding ◽  
Cell Mass ◽  
Myeloproliferative Neoplasm ◽  
Chronic Obstructive ◽  
Thrombotic Risk ◽  
Copd Patients ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Significant Difference ◽  
Secondary Polycythemia

Introduction: Secondary polycythemia is a disorder of increased hemoglobin or hematocrit most often resulting from states of systemic hypoxia such as chronic obstructive pulmonary disease (COPD). Many patients with secondary polycythemia are treated with phlebotomy to reduce hematocrit levels based on recommendations for polycythemia vera (PV)-a myeloproliferative neoplasm characterized by increased red blood cell mass and a greater risk for thromboembolic events-despite the lack of evidence demonstrating whether or not secondary polycythemia patients share this increased risk. While the pro-thrombotic state in PV has been associated with JAK2 allele burden, leukocytosis, and hypercoagulability, similar changes have not been reflected in secondary polycythemia. Because there is limited data on the efficacy or necessity of phlebotomy in patients with secondary polycythemia, our study aims to determine if phlebotomy affects the prevalence of arterial and venous thrombotic events in this patient population Methods: We retrospectively identified patients seen at Rhode Island Hospital/The Miriam Hospital from 1/1/2000 to 1/1/2019 with COPD and a diagnosis of secondary polycythemia via ICD9 coding. Polycythemia was defined as a hemoglobin level greater than 16.0 g/dL in women or 16.5 g/dL in men on at least 2 separate occasions. Data was collected on JAK2 allele status, phlebotomy treatment, co-morbidities, hematologic values, and thrombotic events. Arterial thrombotic events included myocardial infarction (MI), cerebrovascular accident (CVA), and transient ischemic attack (TIA). Venous thrombotic events included deep vein thrombosis (DVT) and pulmonary embolism (PE). Analysis of data was done by chi-square and Mann-Whitney U testing. Results: We identified 151 COPD patients who had a median age of 58 years and hemoglobin of 17 g/dL at time of secondary polycythemia diagnosis. Of these patients, all 58 (38.4%) that underwent testing were negative for the JAK2 V617F allele. Within the study population, 35 (23.2%) of patients were treated with phlebotomy and 116 (76.8%) were not. There was no difference in the median time of follow up for those who did and did not receive phlebotomy (5.6 vs 4.3 years, p=0.46). Phlebotomized patients had a higher hemoglobin (17.1 g/dL vs 16.9 g/dL, p=0.02) and hematocrit (52.2% vs 50%, p=0.007) compared to non-phlebotomized patients. Patients who underwent phlebotomy were more likely to be older (p=0.1) and have obstructive sleep apnea (p=0.06) (Table 1). Thrombotic events were recorded in 22.4% (26/116) of non-phlebotomized patients and 31.4% (11/35) of phlebotomized patients, with no statistically significant difference between the two groups (p=0.28) (Figure 1). Of the 42 patients who had COPD further confirmed by pulmonary function testing (PFT) with a documented post-bronchodilator FEV1/FVC &lt; 0.7, there was also no significant difference in prevalence of total thrombotic events between patients who were and were not treated by phlebotomy. In this group of patients, there were thrombotic events in 18.8% (6/32) of phlebotomized patients and 10% (1/10) of non-phlebotomized patients (p=0.66). There was no statistically significant difference in prevalence of thrombotic events in phlebotomized patients who did and did not achieve phlebotomy goals. Patients who achieved a goal of hematocrit &lt; 52% had a 25% (4/16) prevalence of thromboses compared to 36.8% (7/19) in those who did not (p=0.45). Conclusions: We found no difference between prevalence of arterial, venous, or total thromboses in COPD patients with secondary polycythemia who were phlebotomized compared to those who were not. Similarly, there was no statistically significant reduction in prevalence of thrombotic events in patients who met the phlebotomy hematocrit goal of 52%. Thus, while secondary polycythemia patients often undergo phlebotomy to reduce hematocrit levels, our results provide no clear evidence that phlebotomy is necessary for or effective at reducing thrombotic risk in secondary polycythemia patients. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech: Research Funding; TG Therapeutics: Research Funding. Reagan:Pfizer: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

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