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We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months 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 3 months in 36% vs. 8% ( P = 0.02), at 12 months in 81% vs. 46% ( P = 0.02) and at 18 months 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 6 months onwards, reaching 61% vs. 21% ( P < 0.05) at 36 months. 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. [ABSTRACT FROM AUTHOR]

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‐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. Methods: Forty 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. 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‐α to DAS shows good long‐term efficacy without increased toxicity. [ABSTRACT FROM AUTHOR]

Objectives The direct oral anticoagulants ( DOACs), apixaban and rivaroxaban, are used for anticoagulation treatment. Although biochemical monitoring is not required, severe bleedings caused by DOAC have been reported. We therefore evaluated the chromogenic assay Biophen DiXaI® (Biophen) using plasma from non-bleeding patients in treatment with DOAC and on spiked plasma from patients with ongoing bleeding. Methods The Biophen method was compared with an in-house reference method; liquid chromatography-tandem mass spectrometry ( LC- MS/ MS) using plasma spiked with the compounds ranging from 20 to 1500 μg/L. Furthermore, the methods were compared using plasma from non-bleeding patients in treatment with DOAC (n = 106). In addition, plasma was collected from patients not treated with DOAC, but with ongoing bleeding and tested in spiking experiments (n = 14). Results Analysis of plasma from 106 patients receiving rivaroxaban (n = 91) or apixaban (n = 15) showed agreement and correlation between the methods. Measurement in spiked plasma from patients with active bleeding, however, revealed a 26% overestimation by the assay. Conclusions Our findings show that Biophen is suitable for measuring apixaban and rivaroxaban concentrations in plasma. However, our results in patients with active bleeding show an overestimation of 26%. This should be taken into account when assessing possible intoxication with apixaban and rivaroxaban in patients presenting with bleeding. [ABSTRACT FROM AUTHOR]

Objectives Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg- IFN-α2b) and imatinib may increase the rate of successful discontinuation. Methods In this pilot study, we prospectively stopped imatinib from patients ( n = 12) who had achieved major molecular response ( MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg- IFN-α2b. Molecular monitoring was carried out monthly for BCR- ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed. Results In the monotherapy group, 5/6 patients lost MMR within 4 months. One patient remains to date in MR4.0 61 months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4 months while still receiving Peg- IFN-α2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3 months. One patient is still in sustained MR4.0 at 58 months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells. Conclusions A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2 yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies. [ABSTRACT FROM AUTHOR]

Background: Studies have revealed an association between overweight/obesity and multiple myeloma. However, the factors linking a dysregulated energy metabolism to this disease have not been identified. Adipose tissue produces and secretes the adipokines leptin, adiponectin and resistin, involved in metabolism and cell growth. Methods: We measured the plasma concentrations of these three adipokines in newly diagnosed multiple myeloma as well as in patients with relapse. We further explored the importance of leptin in multiple myeloma by performing gene expression profiling in two myeloma cell lines. Results: At diagnosis, leptin was increased ( P < 0.05) in both female and male patients compared with controls. Adiponectin was reduced ( P < 0.05) among male patients, whereas no significant changes in resistin were noted among any patients. In patients with relapse and treated with thalidomide, no particular adipokine pattern was revealed. Leptin induced the expression of several genes important for cell signaling, growth and viability. Conclusions: The plasma concentrations of leptin and adiponectin, but not resistin, were abnormal in newly diagnosed multiple myeloma. Adipose tissue may modify the growth and metabolism of myeloma cells through adipokine-mediated effects. [ABSTRACT FROM AUTHOR]