scholarly journals Baseline Characteristics of CML Patients Accross Europe - Comparing Real-World Patients with Patient Collectives Included in Clinical Trials

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3160-3160 ◽  
Author(s):  
Michele Baccarani ◽  
Verena Sophia Hoffmann ◽  
Gianantonio Rosti ◽  
Fausto Castagnetti ◽  
Susanne Saussele ◽  
...  
Keyword(s):  
Real World ◽  
Clinical Studies ◽  
Research Funding ◽  
Chronic Phase ◽  
Population Based ◽  
Costal Margin ◽  
Spleen Size ◽  
Newly Diagnosed ◽  
Baseline Characteristics ◽  
Population Based Registry

Abstract Introduction: Most of the knowledge about treatments and outcome of CML patients originates from clinical studies. To get new and unbiased insights in the epidemiology, treatment and outcome of CML, the EUTOS population-based registry of newly diagnosed CML patients was established, - as part of the European Treatment and Outcome Study (EUTOS) for CML. The aim was to collect the data of all adults with newly diagnosed CML, irrespective of treatment and of enrolment in studies. Patients and Methods: The EUTOS population-based registry collected data of newly diagnosed CML patients, 18 years or older, over a specified period of time from 2008 till 2012 living in defined regions. The data were collected by 22 study groups in 20 European countries. Data were gathered via a web-based CRF-system. For comparison we used the already published data from five Company-sponsored registration studies IRIS (O’Brien et.all, NEJM, 2003), TOPS (Cortes et al, JCO, 2009) ENESTnd (Saglio et al, NEJM, 2010), DASISION (Kantarjian et al, NEJM, 2010) and BELA (Cortes et al, JCO, 2012), from three Investigator-sponsored studies GIMEMA (Castagnetti et al, JCO, 2010 and Gugliotta et al, Blood, 2011), French SPIRIT (Preudhomme et al, NEJM, 2010) and German CML IV (Hehlmann et al, JCO, 2011) and from two single referral centers HAMMERSMITH (De Lavallade et al, JCO, 2008) and MDA (Jain et al, Blood, 2013). Results: Till 15.05.2014 2978 patients were registered in the EUTOS Population-based registry. 94.3% of the patients were diagnosed in chronic phase (CP), 3.6% in accelerated phase (AP), and 2.2% in blastic phase (BP). For the calculation of the prognostic scores 361 patients had to be excluded because they were pretreated. For the comparison we used 2350 patients in Chronic Phase with laboratory values before any treatment. 54% of the patients in the EUTOS Population-based registry were male, less than in all studies (56.6 - 60.6%). The median age at diagnosis was 56 years, higher than in all studies (46 - 55). In EUTOS the proportion of patients more than 60 years and more than 65 years old was 40.4 % and 21.9 % respectively. Similar data were rarely reported in all other studies. Median value of the spleen size below costal margin was 0. 46.1% of the patients had a palpable spleen and 15.2% had a spleen size ≥ 10 (spleen size is always reported in cm under costal margin in this abstract). The % of palpable spleen is only reported by IRIS, 25.0% and by the FRENCH Spirit group, 49.8%. The median spleen is only reported by GIMEMA, 2.0. Spleen size ≥ 10 is reported by IRIS, 6.0%, ENESTnd, 12.4% and HAMMERSMITH 25.5%. While the median values for Platelets and Hemoglobin show no big differences, the median WBC in EUTOS is 83.9 x109/l and in the Company-sponsored registration studies: IRIS 18-20 x109/l , in ENESTnd 23-26 x109/l, in DASISION 23-25 x109/l , and in BELA 22-23 x109/l, in the Investigator-sponsored studies: GIMEMA 55 x109/l , in the FRENCH SPIRIT 83-104 x109/l , in the GERMAN CML IV 75-91 x109/l , and in the single referral center study HAMMERSMITH 140 x109/l, clearly indicating that in company-sponsored, registration studies, the reported values of the WBC were not recorded prior to any treatment. The median values for Blasts, Basophils and Eosinophils show also not so big differences. The % of Sokal low risk patients is in EUTOS with 34.5% lower than in all studies (35.2 - 60%) with the exception of HAMMERSMITH 28.9%. Discussion: The EUTOS Population-based registry provides the first European wide real-world series of patients with newly diagnosed Ph+, BCR-ABL+ CML. The age and sex distribution and some baseline characteristics such as Sokal Score as well as median WBC count in the EUTOS population-based registry are different from many prospective studies. This should be taken in due consideration before extrapolating the results of treatment studies to real life. Spleen size, which is known as an important value for prediction, is only very rarely reported in clinical studies. With further follow-up, this registry will provide a population-based insight on treatment, survival, and causes of death. Disclosures Baccarani: Novartis, BMS, Pfizer, Ariad: Consultancy, Honoraria, Speakers Bureau. Hoffmann:Novartis: Research Funding. Rosti:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Castagnetti:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy. Saussele:Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Steegmann:Novartis, BMS, Pfizer: Honoraria, Research Funding. Mayer:Ariad: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Turkina:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Zaritskey:Novartis: Consultancy. Clark:Novartis Pharmaceuticals Corporation: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Porkka:BMS: Honoraria; BMS: Research Funding; Novartis: Honoraria; Novartis: Research Funding; Pfizer: Research Funding. Hehlmann:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding. Hasford:Novartis: Research Funding. Lindoerfer:Novartis: Research Funding.

scholarly journals Demographic and Comorbidity Characteristics of Newly Diagnosed Multiple Myeloma Patients in the United States: A Real World Data Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1301-1301 ◽  
Author(s):  
Yaozhu J Chen ◽  
Ajita P De ◽  
Ze Cong ◽  
Sanjay K Aggarwal ◽  
Rolin L Wade
Keyword(s):  
Real World ◽  
Research Funding ◽  
Index Date ◽  
The United States ◽  
Newly Diagnosed ◽  
Real World Evidence ◽  
The Us ◽  
Skeletal Related Events ◽  
Baseline Characteristics ◽  
Baseline Demographic

Abstract Background Multiple myeloma (MM) remains an incurable plasma cell neoplasm with >20,000 new cases diagnosed annually in the United States (US). The presentation of MM is diverse and the management is guided by disease- and patient- related factors. Real world evidence regarding disease presentation is sparse for newly diagnosed MM (NDMM) patients. The goal of this study was to describe the baseline demographic and clinical characteristics of NDMM patients by linking multiple large claims databases in the US. Methods A retrospective cohort study was conducted by linking the records between 01/01/2006-12/31/2013 from three longitudinal IMS databases (Medical Claims, Pharmacy Prescriptions, and Hospital Charge Master), to reflect a complete treatment continuum for patients in all ages and by all payer types across healthcare settings. Included patients met the following criteria: ≥2 claims with a diagnosis of MM (ICD-9-CM 203.0x) at least 30 days apart between 01/01/2007-12/31/2012 (first MM diagnosis date = index date); provider stability for at least 6 months before and 3 months after index date; aged 18+ as of index date. NDMM patients were identified as those with no MM diagnosis in the 6 months pre-index. Patient baseline characteristics were assessed using data at index for age, gender, geographic region and payer type; 6-month pre-index plus index day data for Charlson Comorbidity Index (CCI); 6-month pre-index data for 32 comorbidities (e.g., cardiac arrhythmia, cerebrovascular disease, chronic kidney disease, diabetes, hypertension, among others); and 5 comorbidity categories (cardiovascular, renal, metabolic, skeletal-related events, and other). Autologous stem cell transplant (ASCT) status was also assessed based on the available follow-up data after initial diagnosis. Patient baseline characteristics were compared between the patients with versus without ASCT after MM diagnosis. Chi-square tests for categorical variables and t-tests for continuous variables (alpha=0.05) were conducted. Results The study cohort of 8,239 NDMM patients had a mean (SD) age of 66.2 (11.3) years at diagnosis, with 56.7% aged 65+; 51.8% were female; and the majority were with commercial (43.3%) or Medicare (42.8%) as payer. Patients with post-index ASCT (n=1,429; 17.3%) were distinctly different from those without (n=6,810; 82.7%): they were younger with a mean (SD) age of 58.1 (8.7) vs. 67.9 (11.1) years, fewer aged 65+, 24.1% vs. 63.5%; fewer female, 47.6% vs. 52.6% (all p<0.001); and the majority (67.5%) of patients who later had ASCT were covered by commercial plans, compared to Medicare as the biggest payer (48.2%) for those who did not have post-index ASCT. NDMM patients had an overall mean (SD) CCI score of 3.1 (1.6). Patients who later received ASCT were healthier than those who did not, with mean (SD) CCI scores of 2.7 (1.4) vs. 3.2 (1.6) (p<0.001). Close to half (47.9%) of all NDMM patients had >1 type of comorbidities at baseline. Figure 1 depicts the baseline comorbidity categories among all NDMM patients as well as the two subsets (with versus without post-index ASCT). Comorbidities were prevalent even before MM diagnosis: 43.9% of patients presented with metabolic comorbidities, 21.4% with cardiovascular diseases, 11.5% with renal conditions, 5.9% with skeletal-related events, and 45.0% with other comorbidities. The patient subset with post-index ASCT had lower comorbidity occurrences compared to those without: 10.5% vs. 23.6% in cardiovascular diseases, 5.9% vs. 12.7% in renal conditions, 32.7% vs. 46.3% in metabolic diseases (all p<0.001), consistent with literature showing that ASCT candidates tend to be younger and have less severe comorbidities. Conclusions This study provided baseline demographic and comorbidity profiles of NDMM patients and showed that the NDMM patient population presented with various comorbidities prior to the first MM diagnosis, suggesting the needs for efficacious, tolerable and safe treatment options for a heterogeneous patient population with complex disease profiles. As expected, patients who had ASCT after initial diagnosis were younger and healthier than those who did not have ASCT. The study findings portray a clearer picture of NDMM patients in the US, and provide clinicians with valuable real world evidence to identify appropriate treatment strategies for these patients. Figure 1 Figure 1. Disclosures Chen: Onyx Pharmaceuticals: Research Funding. De:Onyx Pharmaceuticals: Research Funding. Cong:Onyz Pharmaceuticals: Employment. Aggarwal:Onyx Pharmaceuticals: Employment. Wade:Onyx Pharmaceuticals: Research Funding.

scholarly journals Sequence of Second Generation Tyrosine Kinase Inhibitors (TKIs) in the Treatment of Patients with Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukaemia - Real World Experience in the UK

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3434-3434
Author(s):  
Jenny Byrne ◽  
Joanne Ewing ◽  
Adam J. Mead ◽  
Heather Oakervee ◽  
Gavin Campbell ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Educational Support ◽  
Third Line ◽  
The Uk ◽  
Observation Period

Background: The prognosis of patients with chronic-phase myeloid leukaemia (CML) has drastically improved with the introduction of tyrosine kinase inhibitors (TKIs). During the period of this study, availability of treatment options in the UK were limited and determined by the date reimbursement was granted and when restrictions on the use of individual licensed TKIs were removed. Currently, imatinib, nilotinib and dasatinib are reimbursed for 1st line treatment (1L) with bosutinib and ponatinib reimbursed for 2nd line or subsequent lines of treatment. Aims: The primary aim was to determine the sequence of 2nd generation (2G) TKIs (nilotinib, dasatinib, bosutinib) in patients with chronic-phase Philadelphia chromosome-positive (Ph+) CML who had received their 3rd and subsequent lines of TKIs in a real world UK setting. Methods: A multi-centre, retrospective, chart review was undertaken in the UK from November 2018 to July 2019. To be included, patients had to be aged ≥18 with chronic phase Ph+ CML who had started a third line of TKI treatment between June 2013 and February 2018. Patients were excluded if they had &gt;3-month gap in treatment before progression or relapse, or were treated with a 2G TKI within an interventional clinical study during third line treatment. At each line, molecular responses, cytogenetic responses, duration of therapy and reasons for stopping were recorded until the date of last hospital follow-up or death. Overall survival was determined from date of initiation of 3rd or 4th line TKI therapy until death by any cause. Results: An interim analysis was undertaken for 65 patients from 11 sites. Median age at diagnosis was 53.0 years. 50.8% were male and 49.2% were female. Of these 65 patients, 48 patients were still being treated at the end of observation (29 patients in 3rd, 18 in 4th and 1 in 5th line). Patient demographics are typical of CML populations. Throughout the study, imatinib was 1L treatment of choice for the majority of patients (57/65; 88%) and this held true (21/22; 95%) even when nilotinib and dasatinib were reimbursed for use 1L. Nilotinib was most commonly prescribed in 2L (42/65; 56%), reflecting the greater availability of this drug during the study period. Dasatinib and bosutinib constituted 22% and 4% respectively of 2L treatments. The most frequent sequencing pathway observed was I1-N2-D3 (Table 1, Fig. 1). 19 other pathways at low frequencies were observed across 39 patients. 97% of patients (63/65) achieved an optimal response at any time as defined by the 2013 ELN guidelines (Table 2) during the observation period. Of the 31 (48%) patients who were resistant to 1L, 24 (37%) achieved a response in 2L and of the 7 (10.7%) patients who were resistant to 1L and 2L, 5 (7.7%) achieved a response in 3L. At the end of the observation period, only 2 (3%) patients never achieved a response. In 3L: 29 (45%) patients are still ongoing, 4 died, 3 were lost to follow up and 3 underwent transplantation. In 4L: 18 (69%) are still ongoing, 3 died, and 3 underwent transplantation. Median overall survival for L3 was 21 months and 12 months in L4. In all lines of treatment, the main cause of switching away from imatinib was lack of efficacy (61%), and for all 2G TKIs the main cause was intolerance (66%). During the period when only imatinib was available in 1L, median duration of 1L treatment was longer at 26 months for patients failing to respond vs 9 months when nilotinib and dasatinib were also available. Conclusions: In this UK real-world study, for patients requiring 3 or more lines of treatment, sequencing of TKIs may have been determined by drug reimbursement. As availability of TKIs increased, time to switch therapy decreased for all patients, suggesting that clinicians were following guidelines and switching treatments more readily. However, initial 1L prescribing behaviour has not changed in this observation period despite better access to 2G TKI, and there appears to be a trend of physicians preferring to repeat 2G TKIs treatment sequences that yield a favourable outcome. Disclosures Byrne: Ariad/Incyte: Honoraria, Speakers Bureau. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . Mead:Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; Bristol Myers-Squibb: Consultancy; CTI: Honoraria, Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding. Oakervee:Novartis: Honoraria; Pfizer: Honoraria; Bristol Myers-Squibb: Honoraria. Campbell:Novartis: Consultancy, Other: Educational support; Takeda: Consultancy, Other: Educational support; Bristol Myers-Squibb: Other: Educational support; Roche: Other: Educational support; Celgene: Other: Educational support. Amott:Celgene: Other: Meeting attendance sponsorship . Goringe:Novartis: Consultancy, Other: Speaker. Heartin:Celgene: Other: Speaker's fees; Janssen: Other: Speaker's fees; Takeda: Other: Speaker's fees; Alexion: Other: Speaker's fees; Novartis: Other: Speaker's fees. Dimitriadou:Celgene: Other: Meeting attendance sponsorship . Arami:Takeda: Other: Meeting attendance sponsorship ; Gilead: Other: Meeting attendance sponsorship ; Roche: Other: Meeting attendance sponsorship ; Celgene: Other: Meeting attendance sponsorship . Neelakantan:Novartis: Honoraria; Celgene: Honoraria. Frewin:Novartis: Consultancy, Other: Meeting attendance sponsorship ; AbbVie: Other: Meeting attendance sponsorship . Pillai:Celgene: Honoraria. De Lavallade:BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Incyte biosciences: Honoraria, Research Funding, Speakers Bureau. Cross:Novartis: Consultancy, Research Funding; Incyte: Consultancy. Thompson:Incyte: Employment.

Sa1159 Infection-Related HospitalIzations in Patients Newly Diagnosed With Inflammatory Bowel Disease: Results From a Population-Based Registry

2015 ◽  
Vol 148 (4) ◽  
pp. S-243-S-244
Author(s):  
Wai K. Leung ◽  
Lung-Yi Mak ◽  
Wai Pan To ◽  
Kwan-Lung Michael Ko ◽  
Hai Yun Shi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Population Based ◽  
Newly Diagnosed ◽  
Inflammatory Bowel ◽  
Population Based Registry

Chromosome 1q Amplification Is Associated with a History of Prior Malignancies Among Patients Newly Diagnosed with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2193-2193
Author(s):  
Elizabeth B Lamont ◽  
Andrew J. Yee ◽  
Stuart L. Goldberg ◽  
Andrew D Norden
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Usual Care ◽  
Real World ◽  
Research Funding ◽  
Newly Diagnosed ◽  
History Of ◽  
Equity Ownership ◽  
Prior Malignancy

Background: Over the past 20 years, observational data from usual care clinical oncology settings has been leveraged to inform estimates of cancer treatment-associated benefits and risks among patients not treated on clinical trials. Increasing genomic testing to inform treatment decisions in usual care settings now meaningfully augments traditional observational data, positioning it to provide insights beyond clinical care into tumor biology. We studied patients with newly diagnosed multiple myeloma (MM), comparing cytogenetic test patterns according to history of prior malignancy. Methods: In this retrospective cohort study, we identified 2,380 patients from the COTA real-world database (RWD) who were newly diagnosed with MM in the years 2010-2018. The COTA RWD is a de-identified composite of both abstracted electronic health record and administrative data pertaining to patients receiving their cancer care at one of COTA's clinical oncology practice partners. Among these patients, 1769 (74%) had evidence of MM-associated cytogenetic testing with fluorescent in-situ hybridization (FISH) within the 120 days surrounding their date of diagnosis. The 1,769 patients form the analytic cohort. We compared patients' FISH results for t(4;14), deletion(17p), t(14;16), deletion(13), t(14;20), t(6;14), t(11;14), deletion (1p), and amplification(1q) according to their history of prior malignancy. Results: Within the cohort, 263 prior malignancies were identified in 241 patients (14%, 241/1,769). Two-hundred and twenty-one patients (92%) had one prior malignancy, 28 (7.9%) had two prior malignancies, and one (<1%) had four prior malignancies. The most common prior malignancies were prostate (n=50), breast (n=19), melanoma (n=14), skin (n=13), and cervix (n=6). Amplification of the long arm of chromosome one (amp(1q)) was noted in 31% of patients (75/241) with a prior malignancy vs. 24% of patients (370/1,528) without (chi2 test p=0.02). Overall 25% of patients had amp(1q). No other translocations, amplifications, deletions were associated with prior cancers. A non-parametric test for trend revealed a strong positive association between patients' malignancy count (range 0-4) and amp1q (p<0.01). MM patients with prior lymphomas and prior melanomas also had high rates of amp(1q), though these were not significantly different from patients without these prior malignancies. In a multivariable logistic regression model that adjusted for patient demographic attributes, other known potentially collinear MM poor prognostic factors (i.e., revised ISS stage, IgA sub-type, lambda light chains) and adjusted standard errors for clustering of patients within treatment settings, a history of prostate cancer remained clinically and statistically significantly positively associated with amp(1q) (OR 2.1, 95% CI: 1.9-2.2) as did history of two or more prior malignancies (OR 2.8, 95% CI: 2.3-3.3). Of note, amp(1q) was positively associated with IgA subtype (OR 1.5, 95% CI: 1.3-1.6) and the presence of lambda subtype (OR 1.3, 95%CI: 1.3-1.4). Conclusions: Using RWD, we found that newly diagnosed MM patients with histories of prostate cancer and those with two or more prior malignancies were more likely to have amp(1q), a poor prognostic marker in MM. Gains in 1q have previously been identified among patients with prostate and lymphoid cancers, but to our knowledge this is the first study to identify an association with a prior history of cancer, especially prostate cancer, and amp(1q) in MM. This relationship is worth further exploration of whether there is a common pathway associated with for example risk of prostate cancer and amp(1q) in MM. Clinical trials are less likely to answer this question as patients with prior malignancies are often excluded from enrollment. Overall, the results reported suggest that RWD is an efficient and comparatively inexpensive tool to support research in cancer biology through hypothesis generating and testing analyses of linked real-world phenotypic and genotypic data. Disclosures Lamont: COTA: Employment. Yee:Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy; Adaptive: Consultancy; Amgen: Consultancy, Honoraria. Goldberg:Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership; COTA: Equity Ownership; Bristol-Myers Squibb: Consultancy. Norden:COTA: Employment, Equity Ownership.

The Population-Based ‘real world’ of Low Risk Myelodysplastic Syndromes; Second Interim Analysis of the European LeukemiaNet MDS Registry at 800 Registered New Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1867-1867
Author(s):  
David Bowen ◽  
Alex Smith ◽  
Jackie Droste ◽  
Pierre Fenaux ◽  
Argyris Symeonidis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Creatinine Clearance ◽  
Board Of Directors ◽  
Neutrophil Count ◽  
Real World ◽  
Research Funding ◽  
Population Based ◽  
Low Risk ◽  
Advisory Committees

Abstract Abstract 1867 Background: The European LeukemiaNet MDS Registry programme is the largest and most comprehensive prospective population-based registry of ‘low-risk’ MDS patients followed from diagnosis. Objective: The primary objective of this study is to describe the demographics and the disease-management of newly diagnosed MDS patients within IPSS low and intermediate-1 categories. Methods: The project recruits patients from 107 sites in 11 countries, ranging from 2–25 sites per country and including a high proportion of non-University centres in small cities. Consecutive eligible adult patients are registered within 3 months of diagnosis. Local diagnosis is accepted and a large dataset is collected including laboratory data, clinical information (including co-morbidity and concomitant medication) plus health utility (EQ-5D). Data are entered via a web portal and are source verified by study monitoring visits to sites. Results: As of July 2010, 828 patients are registered; data are presented for the first 800 patients. Recruitment is highest from France (n=237) then UK (104), Greece (99), Spain (92), and Sweden (73). Median age is 74.2 yrs (range 18.7–95.3) and from the four largest recruiting countries is 74.6–77.1 yrs. Sixty one percent of patients are male. Twenty patients are non-Caucasian (n=763). Body mass index is overweight (WHO definition) in 43.4% pts and obese in 18.3%, comparable to WHO data for the general adult population (http://apps.who.int/bmi/index.jsp). RCMD is the largest WHO subgroup (34%), followed by RARS (19%), RA (18.4%), RAEB-1 (12.5%), del5q (5.4%), MDS-U (3.5%) and RAEB-2 (0.5%). All WHO subgroups have male predominance except del5q with a striking female excess (79%). IPSS score (n=743) is 0 (52.3%), 0.5 (33.2%), and 1 (14.4%). 84.5% patients have IPSS ‘good’ cytogenetics. 19% patients have 0 cytopenias, 53% 1 cytopenia, 20% 2 cytopenias and 8% 3 cytopenias. WPSS category (with transfusion dependence assessed at time of registration, n=727) is Very Low (35.5%), Low (39.5%), Intermediate (21%), High (4%). Bone marrow features: mean no. of dysplastic lineages = 1.9, bone marrow ring sideroblasts percent = 0 (60% pts), <15 (11.5%), ≥15<50 (19.2%), ≥50 (9.6%). Median haemoglobin (Hb) concentration at presentation is 10.1 g/dl; 36% values were < 10 g/dl and 10% < 8 g/dl. Hb decreased with age (categorical variable Hb. <13>11.5, <11.5>10, <10; Χ2 test, P<.0001). Mean neutrophil count was 2.8 × 109/l with 27% values <1.5 × 109/l, 16% < 1 × 109/l, and 5% < 0.5 × 109/l. Median platelet count was 184 × 109/l; 5% patients had values < 50 × 109/l and 3% < 20 × 109/l. Platelet count and neutrophil count did not change with age. Median serum erythropoietin (EPO) concentration (n=418) was 49 IU/l, 81% values were <200 IU/l and 7% > 500 IU/l. Mean creatinine clearance was 71 mls/min with a marked reduction with age (P<.0001). Baseline serum EPO correlated with Hb. (r=.37, P<.0001), creatinine clearance (r=.22, P<.0001) and age (r=.1, P<.0001). The relationship between creatinine clearance, baseline EPO and response to EPO therapy will be explored. Discussion: This registry records data from the ‘real world’, namely what the hematopathologists in 100 sites diagnose locally as low-risk MDS and will as such be managed as MDS. Median age is consistent with other population-based data (US Medicare, Yorkshire Haematological Malignancy Research Network [www.hmrn.org]). In comparison with registries from specialist MDS centres, median age is higher and a lower proportion have del(5q) WHO subtype. Conclusion: The ELN registry clearly maps the diagnosis and management of low-risk MDS in routine clinical practice in hospitals large and small, specialist and non-specialist and is a unique resource. Acknowledgments: The Steering Committee (SC) acknowledges the commitment and enthusiasm from all 107 sites contributing high quality data to the project. The SC is also grateful for the funding commitment of Novartis Oncology Europe through the University of Nijmegen. Disclosures: Bowen: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AMGEN: Honoraria; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding. Fenaux:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding. Hellstrom-Lindberg:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Occurrence, Management, and Outcomes In Patients with Pleural Effusion During Dasatinib Treatment for Chronic-Phase Chronic Myeloid Leukemia (CML-CP) In the First-Line Setting: Analysis of the DASISION Trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2282-2282 ◽  
Author(s):  
Kimmo Porkka ◽  
Michele Baccarani ◽  
Andreas Hochhaus ◽  
Hagop Kantarjian ◽  
Satu Mustjoki ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Research Funding ◽  
Chronic Phase ◽  
Risk Scores ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Once Daily ◽  
Management Interventions ◽  
Grade 3

Abstract Abstract 2282 Background: The Phase 3 DASISION trial comparing dasatinib 100 mg once daily with imatinib 400 mg once daily as initial treatment in patients (pts) with newly diagnosed CML-CP has demonstrated superior efficacy and favorable safety of dasatinib after a minimum of 12 months of follow-up (Kantarjian, H, et al. N Engl J Med 2010;362:2260). While fluid retention was more frequent with imatinib than with dasatinib, pleural effusion was seen only with dasatinib. Here, we provide a detailed analysis of pts experiencing pleural effusion, a clinically relevant adverse drug reaction. Methods: 519 pts with newly diagnosed, treatment-naive CML-CP (median disease duration of 1 month) were randomly assigned to either dasatinib 100 mg once daily (259 pts) or imatinib 400 mg one daily (260 pts). Key endpoints included complete cytogenetic response (CCyR), major molecular response (MMR) and safety. All pts were assessed by chest x-ray at baseline and at 6 months after randomization, or more frequently, if indicated clinically. Pts with pleural effusion at baseline were excluded. Pleural effusion was graded according to CTCAE version 3 (grade 1, asymptomatic; grade 2, symptomatic, up to 2 therapeutic thoracenteses; grade 3, symptomatic requiring supplemental oxygen, < 2 therapeutic thoracenteses; grade 4, life-threatening, hemodynamic instability). Results: After a minimum follow-up of 12 months with median treatment duration of 14.3 months (range, 0.3–25.8), 26 (10%, median age, 60 years) of the 258 dasatinib-treated pts (median age, 46 years) experienced pleural effusion. Of the pts with pleural effusion, 6 (23%) had low, 17 (65%) had intermediate and 3 (12%) had high Hasford risk scores. There were no grade 3 or 4 pleural effusion events. All events were grade 1(2%) or grade 2 (8%). Most events (n = 22, 85%) occurred more than 8 weeks after the start of study drug. In pts who had a pleural effusion, the median time to the event was 28 weeks (range, 4–88). Lymphocytosis (defined as peripheral blood lymphocyte count > 3.6 × 109/L) was noted in 11 (42%) of the 26 pts with pleural effusion, as compared to 46 (20%) of 232 pts with no pleural effusion. Pleural effusion was managed by dose modification and/or medical intervention. Therapy was interrupted in 19 pts, and the dose of dasatinib was reduced in 8 pts (4 pts, to 80 mg; 1 pt, to 70 mg; 3 pts, to 50 mg). Twelve pts received diuretics, 7 received corticosteroids, and only 1 pt underwent therapeutic thoracentesis. Only 3 pts (1.2%) discontinued therapy due to pleural effusion (grade 2). Eleven pts who continued dasatinib had resolution of their pleural effusion. Five pts had recurrent effusions. Of the 26 pts with pleural effusion, 24 (92%) achieved a CCyR and 17 (65%) achieved a MMR by 12 months of treatment; the corresponding CCyR and MMR rates in the total pt population were 83% and 46%, respectively Seven of the 8 pts with pleural effusion who reduced their dose achieved CCyR and MMR. Conclusion: In pts with newly diagnosed CML-CP treated with dasatinib as initial therapy, pleural effusion was mild to moderate in severity, and was manageable with dose interruption and/reduction and/or a short course of diuretics and/or corticosteroids. The occurrence of pleural effusion and management interventions did not negatively affect the achievement of CCyR or MMR. These findings are in line with data reported previously for second-line dasatinib in CML pts resistant or intolerant to imatinib (Porkka, K, et al. Cancer 2010;116:377). Furthermore, pleural effusion and peripheral lymphocytosis may be indicative of immune-mediated antitumor activity of dasatinib. Disclosures: Porkka: BMS, Novartis: Consultancy, Honoraria, Research Funding. Baccarani: Novartis, Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hochhaus: Brostol-Myers Squibb, Novartis: Consultancy, Research Funding. Kantarjian: BMS, Pfizer and Novartis: Research Funding; Novartis: Consultancy. Mustjoki: BMS, Novartis: Honoraria. Bradley-Garelik: Bristol-Myers Squibb: Employment, Equity Ownership. Zhu: Bristol-Myers Squibb: Employment. Cortes: Brostol-Myers Squibb, Novartis and Wyeth: Consultancy, Honoraria.

Prognostic Factors in the Blastic and Accelerated Phase of Patients with Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3786-3786
Author(s):  
Young Kwang Chae ◽  
Hagop M. Kantarjian ◽  
Carlos G. Romo ◽  
Clay Whitaker ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Ace Inhibitors ◽  
Research Funding ◽  
Chronic Phase ◽  
Initial Diagnosis ◽  
Favorable Outcome ◽  
Spleen Size ◽  
Platelet Counts ◽  
Concurrent Use

Abstract Abstract 3786 With the advent of TKIs, significant improvement has been made in the survival outcome of CML patients. Many prognostic factors have in identified in chronic phase CML patients. However, prognostic factors in blastic phase (BP) and accelerated phase (AP) of CML patients have not been previously investigated, especially in the era of TKIs. We have analyzed CML patients either been diagnosed in or progressed into BP or AP from 2000 to 2010 enrolled into the clinical trials with different TKIs such as imatinib, nilotinib, dasatinib, and bosutinib at MD Anderson Cancer Center. All demographic, clinicopathologic variables and medication data including TKIs and other medication were collected at the time of the diagnosis of BP or AP. Primary outcomes; progression free survival (PFS) and overall survival (OS) were defined as time from diagnosis of either BP or AP to treatment failure and death, respectively. Among a total of 260 CML patients, mean age was 51.4 (SD 14.1). Males were 59%. Caucasians were 72%; African-Americans, 12%; and Hispanics, 14%. Only 17% reached complete hematologic remission and 62% eventually died during the follow up (mean 4.1 yrs, SD 4.0 yrs). 26% were in BP and 74% in AP. 38 patients were in BP (n=9) or AP (n=29) at initial diagnosis. Mean time from initial diagnosis in chronic phase to BP or AP was 4.1 yrs (0 to 23 yrs). Among BP, 17% had lymphoid BP and 84% myeloid BP. Cytogenetic analysis at diagnosis demonstrated 38% had only Philadelphia chromosome (Ph) present while 62% had other chromosomal abnormalities besides Ph. 30% had received one or more prior TKI by the time of transformation. 64% started on monotherapy imatinib (no prior TKI), 15% nilotinib (86% prior TKI), 14% dasatinib (93% prior TKI), and 3% bosutinib (100% prior TKI); 3.5% received imatinib combined with other agents (57% prior monotherapy with imatinib). Median PFS was 0.7 yr and median OS, 2.4 yrs. Factors linked with worse PFS were higher bone marrow (BM) blast % (HR=1.01, p<0.001), higher peripheral blood (PB) blast % (HR=1.01, p<0.001), higher PB basophil % (HR=1.01, p=0.02), lower PB polymononuclear cells (HR=0.98, p<0.001), lower hemoglobin (HR=0.91, p=0.02), lower platelet counts (HR=0.99, p=0.045), and higher number of prior TKI treatments (HR=1.52, p<0.001). In AP, compared to other TKIs, imatinib was associated with superior PFS (HR=0.63, p=0.03) while nilotinib was linked with inferior PFS (HR=1.81, p=0.04). Dasatinib (HR=1.17, p=0.57) and bosutinib (HR=1.85, p=0.18) did not show difference in PFS. In BP, there was no difference in OS by TKIs. Concurrent use of ACE inhibitors, ARBs, statins, aspirin, or metformin with TKIs was not associated with change in PFS. In multivariate analysis adjusting for the above variables, only prior TKI use was associated with worse PFS (adjusted HR [AHR]=1.57, p=0.001). Imatinib (AHR=0.70, p=0.36) nor dasatinib (AHR=0.67, p=0.11) were no longer associated with favorable or unfavorable PFS. Factors associated with inferior OS were old age (HR=1.02, p<0.001), bigger spleen size (HR=1.03, p=0.001), higher BM blast % (HR=1.02, p<0.001), higher PB blast % (HR=1.02, p<0.001), lower PB polymononuclear cells (HR=0.98, p<0.001), lower hemoglobin (HR=0.80, p<0.001), lower platelet counts (HR=0.99, p=0.008), higher LDH (HR=1.0002, p<0.001), presence of other cytogenetic abnormality besides Ph (HR=1.45, p=0.03),and higher number of prior TKI treatments (HR=1.64, p<0.001). In AP, imatinib was associated with more favorable OS (HR=0.65, p=0.07) compared to others (nilotinib: HR=1.28, p=0.47; dasatinib: HR=1.70, p=0.077; bosutinib: HR=1.09, p=0.88). In BP, there was no difference in OS by TKIs. Concurrent use of ACE inhibitors, ARBs, statins, aspirin, or metformin with TKIs was not associated with change in OS. In multivariate analysis adjusting for the above variables, only age (AHR=1.01, p=0.002) and BM blast% (AHR=1.02, p=0.005) were associated with worse OS. Imatinib was no longer associated with favorable outcome (AHR=1.27, p=0.57). In conclusion, we identified spleen size, blast counts, and number of prior TKI use as major prognostic factors in CML patients in BC or AP. Imatinib was associated with favorable outcome. This is likely due to the fact that patients treated with imatinib had received no prior TKIs while most patients treated with 2nd generation TKI had. Further studies are required to validate our findings in a larger and prospective cohort. 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:Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.

Efficacy and Tolerability of Bosutinib and Imatinib in Older Versus Younger Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia–BELA Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4442-4442 ◽  
Author(s):  
Carlo Gambacorti-Passerini ◽  
Tim H Brümmendorf ◽  
Dong-Wook Kim ◽  
Irina Dyagil ◽  
Hagop M Kantarjian ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Age Groups ◽  
Chronic Phase ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Kaplan Meier ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 4442 Bosutinib (BOS) is an orally active, dual Src/Abl kinase inhibitor with activity and manageable toxicity in the phase 3 BELA trial of patients (pts) with newly diagnosed (≤6 mo) chronic phase (CP) chronic myeloid leukemia (CML). The current analysis of the BELA trial summarizes the activity and tolerability of BOS 500 mg/d and imatinib (IM) 400 mg/d among older (≥65 y; BOS n = 30; IM n = 27) versus younger pts (<65 y; BOS n = 220; IM n = 225). Sokal risk scores were balanced between treatment arms but, as expected, higher among older pts (4% low; 72% intermediate; 25% high) versus younger pts (39% low; 44% intermediate; 17% high). Minimum follow-up duration was 24 mo. BOS was discontinued by 37% of pts (57% older vs 35% younger; P = 0.023); difference between age groups was primarily due to adverse events (AEs; 39% vs 22%; most commonly increased alanine aminotransferase [ALT]). IM was discontinued by 27% of pts (35% older vs 28% younger; P= 0.496); disease progression was the primary reason. In the intent-to-treat population, cumulative rate of complete cytogenetic response (CCyR) by 24 mo in older/younger pts was 70%/80% on BOS and 78%/80% on IM. Median time to CCyR was 24.0 wk for older versus 12.7 wk for younger pts on BOS and 24.4 wk versus 24.7 wk on IM; in younger pts CCyR was achieved significantly faster on BOS versus IM (P<0.001). Among older/younger pts with a CCyR, 57%/79% on BOS and 76%/85% on IM were still on treatment and retained their CCyR as of the data cutoff. Cumulative rates of major molecular response (MMR) by 24 mo in older/younger pts were 53%/60% on BOS and 48%/49% on IM. Median time to MMR was 48.1 wk for older versus 48.0 wk for younger pts on BOS and 60.6 wk versus 84.1 wks on IM; for younger pts MMR was achieved significantly faster on BOS versus IM (P<0.001). Among older/younger pts with a MMR, 63%/84% on BOS and 92%/89% on IM were still on treatment and retained their MMR as of the data cutoff. Kaplan-Meier event-free survival in older/younger pts at 2 y was 100%/91% on BOS and 81%/88% on IM. Kaplan-Meier on-treatment transformation to accelerated/blast phase CML by 2 y was 0% for older and 2% (4 transformations) for younger pts on BOS (4 total), and 9% (2 transformations) for older and 5% (11 transformations) for younger pts on IM (13 total). Kaplan-Meier overall survival in older/younger pts at 2 y was 100%/97% on BOS and 92%/95% on IM. The majority of deaths were due to disease progression (BOS, n = 6; IM, n = 10); few deaths due to AEs on BOS (n = 1) or IM (n = 2) were reported, none treatment related. BOS was associated with higher rates of gastrointestinal TEAEs, elevated ALT and aspartate aminotransferase (AST), and pyrexia; IM was associated with higher rates of musculoskeletal TEAEs and edema (Table). Rates of common TEAEs were generally similar or higher among older pts. Pleural/pericardial effusion occurred in 6 (21%) older pts (3/6 with treatment-related events; median event duration, 36.5 d) versus 5 (2%) younger pts (all with treatment-related events) on BOS, and in no IM pts. Overall grade 3/4 TEAEs were more frequent among older pts on both BOS and IM, as was dose modification (Table). Grade 3/4 lab abnormalities of elevated ALT (BOS, 18% older/24% younger; IM, 4% each) and AST (BOS, 7%/12%; IM, 4% each) were more frequent with BOS versus IM, but similar between age groups. Grade 3/4 lab abnormalities of neutropenia were more frequent with IM (23% older/22% younger) versus BOS (11% each) regardless of age; grade 3/4 anemia (6%-14%) and thrombocytopenia (14%-23%) were generally similar regardless of age or treatment arm. In conclusion, BOS demonstrated activity in both older and younger pts with newly diagnosed CP CML. Although the frequency of certain toxicities as well as treatment discontinuations due to TEAEs was higher among older pts, the toxicity profile of BOS remained manageable and distinct from that of IM regardless of age. Event, % BOS IM ≥65 y (n = 28) <65 y (n = 220) ≥65 y (n = 26) <65 y (n = 225) Non-hematologic TEAEsa     Diarrhea 86 68 46 22     Rash 36 22 27 18     Nausea 36 32 31 37     Vomiting 32 32 19 15     Dyspnea 32 5 12 3     Pyrexia 29 17 4 13     Elevated ALT 29 32 15 8     Elevated AST 25 27 15 8     Elevated lipase 25 12 19 10     Headache 21 12 8 12     Asthenia 21 5 4 7     Dyspepsia 14 6 23 5     Muscle spasms 14 3 35 21     Periorbital edema 7 <1 35 12 Any grade 3/4 TEAE 89 65 73 56 Dose reduction due to AE 64 40 42 18 Dose interruption due to AE 89 63 69 42 Treatment discontinuation due to AE 39 22 8 9 All treated pts were included in the safety analyses. a Includes TEAEs reported for ≥20% of older or younger pts. Disclosures: Gambacorti-Passerini: Pfizer Inc: Consultancy, Research Funding; Novartis, Bristol Myer Squibb: Consultancy. Brümmendorf:Bristol Myer Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; Patent on the use of imatinib and hypusination: Patents & Royalties. Kim:BMS, Novartis, Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Pfizer Inc: Research Funding. Pavlov:Pfizer Inc: Employment, Equity Ownership. Gogat:Pfizer Inc: Employment, Equity Ownership. Duvillie:Pfizer Inc: Employment. Shapiro:Pfizer Inc: Employment, Equity Ownership. Cortes:Novartis, Bristol Myers Squibb, Pfizer, Ariad, Chemgenex: Consultancy, Research Funding.

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