scholarly journals Potential to Improve Therapy of Chronic Myeloid Leukemia (CML), Especially for Patients with Older Age: Incidence, Mortality, and Survival Rates of Patients with CML in Switzerland from 1995 to 2017

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6269
Author(s):  
Michael Daskalakis ◽  
Anita Feller ◽  
Jasmine Noetzli ◽  
Nicolas Bonadies ◽  
Volker Arndt ◽  
...  

Background: Tyrosine kinase inhibitors (TKI) substantially improved chronic myeloid leukemia (CML) prognosis. We aimed to describe time period- and age-dependent outcomes by reporting real-world data of CML patients from Switzerland. Methods: Population-based incidence, mortality, and survival were assessed for four different study periods and age groups on the basis of aggregated data from Swiss Cantonal Cancer Registries. Results: A total of 1552 new CML cases were reported from 1995 to 2017. The age-standardized rate (ASR) for the incidence remained stable, while the ASR for mortality decreased by 50–80%, resulting in a five-year RS from 36% to 74% over all four age groups. Importantly, for patients <60 years (yrs), the five-year RS increased only in earlier time periods up to 92%, whereas for older patients (+80 yrs), the five-year RS continued to increase later, however, reaching only 53% until 2017. Conclusions: This is the first population-based study of CML patients in Switzerland confirming similar data compared to other population-based registries in Europe. The RS increased significantly in all age groups over the last decades after the establishment of TKI therapy. Interestingly, we found a more prominent increase in RS of patients with older age at later observation periods (45%) compared to patients at younger age (10%), implicating a greater benefit from TKI treatment for elderly occurring with delay since the establishment of TKI therapy. Our findings suggest more potential to improve CML therapy, especially for older patients.

2011 ◽  
Vol 29 (18) ◽  
pp. 2514-2520 ◽  
Author(s):  
Magnus Björkholm ◽  
Lotta Ohm ◽  
Sandra Eloranta ◽  
Åsa Derolf ◽  
Malin Hultcrantz ◽  
...  

Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% Cls) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.


Blood ◽  
2011 ◽  
Vol 117 (21) ◽  
pp. 5591-5599 ◽  
Author(s):  
Gabriele Gugliotta ◽  
Fausto Castagnetti ◽  
Francesca Palandri ◽  
Massimo Breccia ◽  
Tamara Intermesoli ◽  
...  

AbstractThe median age of chronic myeloid leukemia (CML) patients is ∼ 60 years, and age is still considered an important prognostic factor, included in Sokal and EURO risk scores. However, few data are available about the long-term outcome of older patients treated with imatinib (IM) frontline. We analyzed the relationship between age and outcome in 559 early chronic-phase CML patients enrolled in 3 prospective clinical trials of Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party, treated frontline with IM, with a median follow-up of 60 months. There were 115 older patients (≥ 65 years; 21%). The complete cytogenetic and major molecular response rates were similar in the 2 age groups. In older patients, event-free survival (55% vs 67%), failure-free survival (78% vs 92%), progression-free survival (62% vs 78%), and overall survival (75% vs 89%) were significantly inferior (all P < .01) because of a higher proportion of deaths that occurred in complete hematologic response, therefore unrelated to CML progression (15% vs 3%, P < .0001). The outcome was similar once those deaths were censored. These data show that response to IM was not affected by age and that the mortality rate linked to CML is similar in both age groups. This trial was registered at www.clinicaltrials.gov as #NCT00514488 and #NCT00510926.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4432-4432
Author(s):  
Kudrat Abdulkadyrov ◽  
Elza Lomaia ◽  
Natalia Lazorko ◽  
Vasiliy Shuvaev ◽  
Alla Abdulkadyrova ◽  
...  

Abstract Abstract 4432 Background: The incidence of chronic myeloid leukemia (CML), reported from some population based registries, varies significantly. CML is known as age-dependent disease, so population age structure may strongly influent on the data. For international comparisons several systems for age-standardization are using in epidemiological studies. We conducted our retrospective study to reveal differences in CML incidence rates on the basis of calculation – crude or age-adjusted according to different population standards in St. Petersburg and Leningrad region. Methods: In 2005 the database of Ph- and/or bcr-abl- positive CML patients (pts) was conducted in St. Petersburg and Leningrad region. Since then the data from all newly diagnosed CML patients were included prospectively on population basis. The database was updated at least bi-annually. The data were obtained from hematologists, as general practitioners and private physicians are not licensed to treat oncohematological disorders. The data were double checked from the list of Imatinib distribution (the only drug reimbursed for first line treatment). To calculate crude CML incidence rate we use the data of the general census of the population in Russia in 2010 (the whole population of our region is 6596434 with population in age 15 and above 5821133). For age-adjusted CML incidence rate we use three of currently existing standards: The Segi (“World”), The Scandinavian (“European”) and the WHO standard (based on world average population between 2000–2025). Results: There are 258 (242 in chronic, 9 in accelerated and 7 in blastic phases) CML adult (15 years and above) pts, registered during 2006–2011. The median age is 53 years (48,5 and 55,5 years for men and women respectively). Sokal score was evaluable in 209 pts. It is low in 37%, intermediate in 35% and high in 28% pts. The crude CML incidence rate is slightly higher in men than in women with ratio 1,2:1. Mean annual crude CML incidence rate was 0,65 per 100 000 whole population of Saint Petersburg and Leningrad region, but it was 0,74 in adult population (15 years old and above). Mean annual CML incidence rates in the same age groups were slightly higher in all three standardized systems: 0,94 in Segi, 0,84 in Scandinavian and 0,88 in WHO standard populations. CML incidence rates in all age groups are presented in the table 1. CML incidence rate was lowest in young pts. It was unexpectedly very low in senior pts. CML incidence rates nearly for all age groups were slightly higher in St. Petersburg than in the Leningrad region. The majority of pts (98%) were treated with Imatinib (93% first or second line) or other tyrosine kinase inhibitors (5% first line-in international clinical trials, 18% after Imatinib failure or intolerance). Stem cell transplantation was performed only in 8/258 (3%) pts. Only 25235 (7,5%) evaluable pts progressed from chronic to advanced phases. Only 29/258 (11%) pts dead mostly due to CML (21 CML related deaths were reported). Estimated 5 years overall survival is 91,5%. Mean annual overall CML pts death rate was 1,9% (mean annual death rate between 2006–2010 in whole population of our region was 1,6%). Mean pts accumulated very fast - annual CML prevalence increasing rate between 2005–2011 was more than 14% (Picture 1). Conclusions: CML incidence both crude and age-adjusted in our population based registry is nearly the same in young and middle age, but much lower in senior (65 years and above) pts groups in comparison with published data from other registries which probably represents peculiarities of health system rather than real incidence. In the tyrosine kinase inhibitors era CML patients death rate is very low (nearly the same as in whole population) and CML pts is accumulated very fast in our region. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2955-2955 ◽  
Author(s):  
M. Rohrbacher ◽  
U. Berger ◽  
A. Hochhaus ◽  
G. Metzgeroth ◽  
K. Adam ◽  
...  

Abstract Epidemiological information on chronic myeloproliferative disorders (CMPD), notably Philadelphia (Ph) and/or bcr/abl positive chronic myeloid leukemia (CML), is rare. National cancer registries and clinical trials differ with regard to median age of CML patients by 10 to 20 years (Table). Therefore, an evaluation was conducted in a defined area in Germany between 1998 and 2000 to determine incidences and compare clinical characteristics of Ph and/or bcr/abl positive CML patients participating and not participating in trials. 68 (37.4%) hospitals and 241 specialty practices (16.4%) reported 893 newly diagnosed CMPD patients. CML patients represented 24.9% of all cases with CMPD. The crude incidence of CML cases (n=218) was 0.79, that of the 172 Ph and/or bcr/abl positive CML cases 0.62 and that of CMML (n=61) 0.22. The incidence of CML and CMML cases combined was 1.01. 110 (64.0%) of the 172 Ph and/or bcr/abl positive CML patients participated in clinical studies, mainly CML Studies III and IIIA of the German CML Study Group. Median age was significantly different between patients participating and not participating in clinical trials: (54.1 vs. 64.8 years, p=0.0001). The chance for a Ph and/or bcr/abl positive CML patient < 65 years to be enrolled in a clinical study was 3.8 times higher than for a CML patient ≥ 65 years (OR=3.8, CI: 1.9–7.3). Male patients had a slightly higher probability to be enrolled in a study than females (OR=1.5 (CI: 0.8–2.8)). Our data indicate that 36% of the Ph and/or bcr/abl positive CML patients registered in a defined area of Germany are not treated in clinical trials, that elderly patients have a lower probability to be included in trials than younger patients and that patients participating in trials are 10.7 years younger than those who do not. Age of CML Patients in Population based Registries and in Clinical Trials A) Registries Age mean (years ± S.D.) / Thames Cancer Registry, U.K. 65 (20–98) SEER Cancer Statistics Review, 1975–2004 68 (range not available) SEER cancer statistics review, 1973–1998 64 (range not available) B) Trials The Italian Cooperative Study Group on Chronic Myeloid Leukemia. N Engl J Med 1994 48 ± 14 Hehlmann et al., Blood 1994 48 (17–85) Guilhot et al., N Engl J Med 1997 50 (7–70) Hasford et al., JNCI 1998 49 (10–85) The Benelux CML Study Group. Blood 1998 56 (20–83) Baccarani et al., Blood 2002 45 ± 13 Hehlmann et al., Leukemia 2003 48 (10–83) O’Brien et al., N Engl J Med 2003 50 (18–70) Hehlmann et al., Blood 2007 49 (11–90)


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 205-205
Author(s):  
Magnus Bjorkholm ◽  
Lotta Ohm ◽  
Sandra Eloranta ◽  
Åsa Rangert Derolf ◽  
Malin Hultcrantz ◽  
...  

Abstract Abstract 205 Background: Little progress in terms of improving survival in patients with chronic myeloid leukemia (CML) was made until the introduction of interferon alpha and allogeneic stem cell transplantation for selected patients in the 1980s. The management changed dramatically with the development of imatinib mesylate, the first tyrosine kinase inhibitor (TKI) that targets the BCR-ABL1 oncoprotein. In Sweden clinical trials started in December 2000 and the drug was approved for clinical use in November 2001. This study evaluates the impact of treatment developments in CML by studying temporal trends in short-term and long-term excess mortality in a population-based setting. Materials and Methods: Using data from the nationwide, population-based Swedish Cancer Registry and Swedish population life-tables stratified by age, sex, and calendar time we characterized trends in relative survival for all patients diagnosed with CML in Sweden 1973–2008 (n=3,173; 1,796 men and 1,377 women; median age 62 years). Patients were categorized into five age groups (<50, 50–59, 60–69, 70–79 and >79 years) and five calendar periods (1973-1979, 1980–1986, 1987–1993, 1994–2000 and 2001–2008). Six hundred and nine stem cell transplants (539 allogeneic and 70 autologous) were reported to the EBMT registry during the study period. Results: Incidence remained stable over time with a consistent male predominance. Relative survival improved with calendar period with the greatest improvement in the last two calendar periods (figure). Five-year cumulative relative survival ratios (RSRs; 95% confidence intervals) were 0.21 (0.17-0.24), 0.23 (0.20-0.27), 0.37 (0.33-0.41), 0.54 (0.50-0.58) and 0.80 (0.75-0.83) in the five calendar periods, respectively. Ten-year RSRs were 0.06 (0.04-0.08) and 0.78 (0.73-0.83) in the first and last calendar periods, respectively. This improvement was confined to age groups up to 79 years of age but most pronounced in patients below 60 years. The 5-year RSRs for patients diagnosed 2001–2008 were 0.91 (0.85-0.94), 0.87 (0.78-0.92), 0.82 (0.72-0.90), 0.75 (0.61-0.86), and 0.25 (0.10-0.47) for the five age groups, respectively. Older age at diagnosis and male sex were associated with significantly higher excess mortality rates in models adjusted for potential confounding factors. Conclusion: In this large population-based study including > 3,000 CML patients survival increased significantly after 2001 (when imatinib mesylate was approved for clinical use in Sweden) for patients up to 79 years of age. Future studies are needed to assess if very old (>79 years) CML patients may benefit from an increased use of TKIs. Also newly introduced, targeted treatment options for CML need to be evaluated in future population-based studies. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16084-e16084
Author(s):  
Vinay Mathew Thomas ◽  
Basil Baby ◽  
Kevin Wang ◽  
Feitong Lei ◽  
Quan Chen ◽  
...  

e16084 Background: Colorectal cancer (CRC) accounts for 10% of global cancer deaths yearly. It is postulated that the incidence rates are rising in developing countries like India. We present a comprehensive overview of colorectal cancer incidence in India from various regions from 2004 to 2014. Methods: We obtained data on CRC incidence from the Population Based Cancer Registries (PBCR) of the National Cancer Registry Program. We calculated age-standardized incidence rates (to WHO World Standard Population 2000) for five-year age groups for period of diagnosis (2004-05, 2006-08, 2009-11, and 2012-14). Results: From 2004 to 2014, CRC incidence rates in India increased by 20%. During 2004-2005, the incidence rate of CRC was 5.8 per 100,000 persons. It increased to 6.9 during 2012-2014. Conclusions: CRC rates are rising in India. Even though the absolute rates are low in the Indian population, the rising rates pose a problem in rising cancer morbidity in India. The rising rates can be attributed to changing lifestyles that include consumption of calorie-rich and low fibre diet, excessive use of red meat and processed foods, and physical inactivity. There is a need for cost-effective strategies to enable early diagnosis for colorectal cancer in India. Affordable and equitable treatment will help increase the 5-year survival rates of colorectal cancers. [Table: see text]


2015 ◽  
Vol 56 (6) ◽  
pp. 1771-1777 ◽  
Author(s):  
Amélie Penot ◽  
Pierre-Marie Preux ◽  
Sandra Le Guyader ◽  
Albert Collignon ◽  
Aurélie Herry ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2099-2099
Author(s):  
John L. Villano ◽  
Stephen Todd Anderson ◽  
Therese A. Dolecek

2099 Background: Although meningioma is the most common tumor in the central nervous system (CNS), the incidence, epidemiology, and clinical outcomes have historically been poorly defined. Our analysis follows the implementation of Public Law 107–260, the Benign Brain Tumor Cancer Registries Act mandating collection of non-malignant meningiomas. Methods: Surveillance Epidemiology End Results Program (SEER) 18 registries research data on cases diagnosed during 2004-2009 with meningioma (ICD-O-3 histology codes 9530-9534 & 9537-9539) in brain or CNS primary site (C70.0-72.9, 75.1-75.3 ) were analyzed. Population-based statistics were generated using SEER*Stat 8.0.1 software. Results: A total of 35,302 cases (34,718 non-malignant; 584 malignant) were available providing a rate of 7.18/100,000, with meningioma, NOS (9530/0) the most common histology. Rates increased with age (0.13/100,000, 0-19 years; 37.78/100,000, 75+ years). The annual percentage change in incidence rates showed a statistically significant increase of 2.57% over 2004-2009. Significant increases were also observed for males, females, whites, blacks, non-Hispanics, and older age groups. The gender ratio M:F was 0.35 in the 0-49 age group and 0.48 in the 50+ age. Primary site location included cerebral meninges (83%) with almost 5% in the spinal meninges. 51% of cases were diagnosed pathologically versus imaging. However, diagnosis among 85% of spinal cases was surgically based. Older age and females were less likely to have a surgical diagnosis. 3.4% received radiation therapy (RT) with 97% receiving RT following surgery. For grade III or malignant cases, 22% received RT, and in grade 1 and 2 nearly 97% of cases did not receive RT, with older age groups less likely to receive RT. Overall survival was high, except for grade 3 or malignant cases where 5 year relative survival was 61.7%. Conclusions: Our analysis following Public Law 107–260 demonstrates an increasing incidence of meningiomas and provides new information, including a decrease in the gender difference with age. Clinical diagnosis is common and higher in women and older adults. Use of RT is low, even in malignant meningiomas, and employed following surgery. These observations were similar for white and black cases.


Leukemia ◽  
2021 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Timothy P. Hughes ◽  
Richard A. Larson ◽  
Dong-Wook Kim ◽  
Surapol Issaragrisil ◽  
...  

AbstractIn the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.


Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Andreas Hochhaus

Abstract Elucidation of the pathogenesis of chronic myeloid leukemia (CML) and the introduction of tyrosine kinase inhibitors (TKIs) has transformed this disease from being invariably fatal to being the type of leukemia with the best prognosis. Median survival associated with CML is estimated at > 20 years. Nevertheless, blast crisis occurs at an incidence of 1%-2% per year, and once this has occurred, treatment options are limited and survival is short. Due to the overall therapeutic success, the prevalence of CML is gradually increasing. The optimal management of this disease includes access to modern therapies and standardized surveillance methods for all patients, which will certainly create challenges. Furthermore, all available TKIs show mild but frequent side effects that may require symptomatic therapy. Adherence to therapy is the key prerequisite for efficacy of the drugs and for long-term success. Comprehensive information on the nature of the disease and the need for the continuous treatment using the appropriate dosages and timely information on efficacy data are key factors for optimal compliance. Standardized laboratory methods are required to provide optimal surveillance according to current recommendations. CML occurs in all age groups. Despite a median age of 55-60 years, particular challenges are the management of the disease in children, young women with the wish to get pregnant, and older patients. The main challenges in the long-term management of CML patients are discussed in this review.


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