Therapy of Early Chronic Phase Chronic Myeloid Leukemia (CML-CP) with Lower Dose Dasatinib
Dasatinib is a potent tyrosine kinase inhibitor (TKI) of BCR-ABL. Approved dose in the chronic phase is 100mg daily. This is however associated with notable side effects mainly myelosuppression and pleural effusion, leading to dose reductions/interruptions.
Identifying non-adherence in chronic myeloid leukemia (CML) remains a challenge. Tyrosine kinase inhibitor adherence was measured by electronic monitoring and BAASIS © self-report in 55 CML patients over 4 months. The BAASIS© had 67% sensitivity and 71% specificity for diagnosing non-adherence. The BAASIS© and the risk factors for non-adherence found in this study provide a basis for identifying non-adherent CML patients.
To study how ponatinib is used outside clinical trials, we identified 37 patients with CML in 7 medical centers; all failed at least one prior TKI. The median age was 43 years (range: 9 - 82) and the overall response rate was 85%. Hence, in real-life, ponatinib is reserved for exceptionally young patients. Responses are expected even in heavily pretreated patients.
CONCLUSION: In real life, ponatinib is a "niche-drug" reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates. PMID: 29773429 [PubMed - as supplied by publisher]
In the present study, we identified 37 patients with chronic myeloid leukemia in 7 medical centers to study how ponatinib is used outside of clinical trials. At least 1 previous tyrosine kinase inhibitor had failed in all 37 patients. Their median age was 43 years (range, 9-82 years), and the overall response rate was 85%. Outside of clinical trials, ponatinib has been reserved for exceptionally young patients; however, responses can be expected even in heavily pretreated patients.
Treatment-free remission after discontinuation of tyrosine kinase inhibitor therapy is now an emerging treatment goal in patients with chronic myeloid leukemia, who have achieved a deep and stable response to treatment. While guidance are now available, considering patients ’ questions on this progressive concept have yet to be addressed. The overall aim of this European Steering Group is a patient-centered approach that educates patients on their treatment options, including treatment-free remission, facilitates better patient-physician relationships, and meets pati ents’ emotional and psychological needs.
CONCLUSIONS: Our analysis provided no convincing evidence for an increased risk of death from a range of hematolymphopoietic cancers in workers exposed to high or medium levels of ELF magnetic fields. However, we observed an increased risk of acute myeloid leukaemia in workers exposed to high levels for a longer duration. Observed risks are in line with meta-analysed previous reports on ELF-MF exposure and AML risk, with a summary relative risk of 1.21 (95%CI 1.08-1.37). PMID: 29587222 [PubMed - as supplied by publisher]
Conclusion These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of at least 1 year is feasible, particularly for patients with no prior history of imatinib resistance. In addition, the NK cell count was associated with TFR. (DADI trial; UMIN000005130).
Conclusion After a median follow-up of 8 years, imatinib was found to induce long survival with manageable side effect in adult Saudi patients with CML-CP. Micro-Abstract Imatinib (Gleevec) was the first drug to target the breakpoint cluster region (BCR)-Abelson (ABL) tyrosine kinase and hence became the first line of therapy for patients with chronic myeloid leukemia. It provides a high rate of remission and survival benefits with minimal side effects.
Conclusion In this study, we investigated the effect of pharmacogenetics in the context of a CML treatment discontinuation trial. The transcript levels of the efflux transporter ABCG2 predicted TFR after TKI discontinuation. Micro-Abstract Whithin the EURO-SKI trial, 132 chronic phase CML patients discontinued imatinib treatment. RNA was isolated from peripheral blood in order to analyze the expression of MDR1, ABCG2 and OCT1. ABCG2 was predictive for treatment-free remission in Cox regression analysis. High transcript levels of the ABCG2 efflux transporter (>4.5‰) were associated with a twofold higher risk of relapse.
We describe the results of a prospective trial of the discontinuation of second-line dasatinib treatment in chronic myeloid leukemia patients who maintained a deep molecular response for> 1 year. The treatment-free remission rate at 36 months was 44.4%. High natural killer cell counts before discontinuation correlated significantly with successful therapy discontinuation.