| 1. |
- Flygt, Hjalmar, et al.
(författare)
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Long-term tolerability and efficacy after initial PegIFN-alpha addition to dasatinib in CML-CP : Five-year follow-up of the NordCML007 study
- 2021
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Ingår i: European Journal of Haematology. - : Wiley-Blackwell. - 0902-4441 .- 1600-0609. ; 107:6, s. 617-623
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Treatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-alpha in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-alpha (PegIFN-alpha) in combination with dasatinib (DAS) in CML-CP. Methods Forty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 mu g/wk of PegIFN-alpha was added and increased to 25 mu g/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data. Results After 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study. Conclusion Initial addition of PegIFN-alpha to DAS shows good long-term efficacy without increased toxicity.
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| 2. |
- Flygt, Hjalmar, et al.
(författare)
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Long-term tolerability and efficacy after initial PegIFN-α addition to dasatinib in CML-CP : Five-year follow-up of the NordCML007 study
- 2021
-
Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 107:6, s. 617-623
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTreatment-free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML-CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon-α in addition to TKI has shown promising efficacy but with dose-dependent toxicity and discontinuations. NordCML007 was initiated to study the efficacy and safety of low dose pegylated IFN-α (PegIFN-α) in combination with dasatinib (DAS) in CML-CP.MethodsForty patients with newly diagnosed CML-CP were given DAS upfront. After month 3 (M3) 15 μg/wk of PegIFN-α was added and increased to 25 μg/wk from M7 until M15. DAS treatment was continued and adverse events and BCR-ABL1 qRT-PCR values were reported yearly after M24. Results from M1 to M18 have previously been published, and here we present long-term data.ResultsAfter 5 years of follow-up, there were no suspected unexpected serious adverse reactions, no increase in serosal effusions, no disease progressions and no CML-related deaths. Rates of MR3.0 (MMR), MR4.0 and MR4.5 were 84.6%, 64.1% and 51.3% respectively at M60, and 95% of patients reached MMR at some point during the study.ConclusionInitial addition of PegIFN-α to DAS shows good long-term efficacy without increased toxicity.
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| 3. |
- Gunnarsson, Niklas, et al.
(författare)
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Population-based assessment of chronic myeloid leukemia in Sweden : striking increase in survival and prevalence
- 2016
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 97:4, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- The clinical outcome for patients with chronic myeloid leukemia (CML) has improved dramatically following the introduction of tyrosine kinase inhibitors. An improved survival, combined with a constant incidence, is expected to increase the prevalence of CML. However, data on the prevalence of CML remain scarce. We examined the overall and relative (age and gender matched) survival and assessed the past, present, and projected future prevalence of CML in Sweden. Data on all patients diagnosed with CML between 1970 and 2012 were retrieved from the Swedish Cancer Register and the Swedish Cause of Death Register. The 5-year overall survival increased from 0.18 to 0.82, during the observed time period. Between 2006 and 2012, the 5-year relative survival was close to normal for 40-year-old, but considerably lower for 80-year-old CML patients. The observed prevalence tripled from 1985 to 2012, from 3.9 to 11.9 per 100 000 inhabitants. Assuming no further improvements in relative survival, the prevalence is projected to further increase by 2060 to 22.0 per 100 000 inhabitants (2587 persons in Sweden). The projected dramatic increase in CML prevalence has major medical and health economic implications and needs to be considered in planning how to organize future care of CML patients.
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| 4. |
- Hjorth-Hansen, Henrik, et al.
(författare)
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Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)
- 2015
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 94:3, s. 243-250
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Tidskriftsartikel (refereegranskat)abstract
- We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100mg QD or imatinib 400mg QD and report outcome as an intention-to-treat analysis with 36months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3months in 36% vs. 8% (P=0.02), at 12months in 81% vs. 46% (P=0.02) and at 18months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6months onwards, reaching 61% vs. 21% (P<0.05) at 36months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.
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| 5. |
- Larfors, Gunnar, et al.
(författare)
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Despite warnings, co-medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but XS004, a novel oral dasatinib formulation, provides reduced pH-dependence, minimizing undesirable drug-drug interactions.
- 2023
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Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dasatinib and other tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, as a lipophilic weak base, crystalline monohydrate, dasatinib (Sprycel®) is poorly soluble, rendering a pH-dependent absorption and a highly variable bioavailability. Thus, co-medication with proton pump inhibitors (PPI) profoundly impairs dasatinib uptake and is clearly recommended against. XS004 is a novel oral immediate release and amorphous solid dispersion (ASD) formulation of dasatinib and is bioequivalent to the original crystalline dasatinib at 30% lower dosages. XS004 is designed to mitigate gastric pH dependency, thus optimizing absorption and bioavailability.METHODS: We investigated the prevalence of dasatinib and PPI co-medication among chronic-phase CML patients in a real-world setting and assessed the plasma pharmacokinetics (PK) of XS004 with and without PPI co-medication (omeprazole) in healthy volunteers.RESULTS: Using the Swedish CML and Prescribed Drug Registers, we identified 676 TKI-treated CML patients; 320 (47%) had been prescribed PPI at some point after CML diagnosis. Among dasatinib-treated patients, the 2-year cumulative PPI co-medication was 24%. Interestingly, the 5-year overall survival was significantly lower for TKI-treated CML patients with versus without PPI co-medication (79% vs. 94%; hazard ratio 3.5; 95% confidence interval, 2.1-5.3; p < .0001). When assessing PK of XS004, neither Cmax nor area under the plasma concentration curve levels in plasma were significantly altered by the PPI co-medication.CONCLUSION: In conclusion, despite warnings, PPI co-medication is common among dasatinib-treated CML patients in a real-world setting. The new XS004 ASD formulation of dasatinib provided, in contrast to original crystalline dasatinib, superior pH independence with stable bioavailability, thereby minimizing drug-drug interactions. This may improve the long-term efficacy and tolerability of dasatinib in CML.
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| 6. |
- Larfors, Gunnar, et al.
(författare)
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The impact of socio-economic factors on treatment choice and mortality in chronic myeloid leukaemia
- 2017
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 98:4, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the influence of socio-economic variables on treatment selection and survival of patients with chronic myeloid leukaemia (CML).METHODS: Using information available in population-based Swedish registries, we evaluated indices of health, education and economy from the 980 patients in the Swedish CML register diagnosed between 2002 and 2012. Apart from internal comparisons, five age-, gender- and region-matched control subjects per patient served as control cohort. Median follow-up time from CML diagnosis was 4.8 years.RESULTS: Among patients with CML, low personal or household income, short education, living alone, poor performance status and high age (>60 years) were significantly associated with an inferior survival (in univariate analyses). However, similar findings were noted also in the matched control group, and in comparisons adjusted for calendar year, age and performance status, socio-economic variables were not significantly associated with CML survival. Meanwhile, both education and income were independently linked to TKI treatment overall and to upfront treatment with second-generation TKIs.CONCLUSIONS: In conclusion, socio-economic conditions were associated with survival in the studied CML cohort but these associations could be explained by differences at baseline. Meanwhile, socio-economic conditions appeared to influence treatment choice.
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| 7. |
- Söderlund, Stina, et al.
(författare)
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Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era : a report from the Swedish CML register
- 2017
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 98:1, s. 57-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment.METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment.RESULTS: The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively.CONCLUSION: In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression.
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