Development of <i>BRAFV600E</i>-positive acute myeloid leukemia in a patient on long-term dabrafenib for multisystem LCH

Salek, Marta; Oak, Ninad; Hines, Melissa; Maciaszek, Jamie L.; Tatevossian, Ruth; Sharma, Akshay; Nichols, Kim E.; Campbell, Patrick

doi:10.1182/bloodadvances.2021006229

Cited by 8 publications

(16 citation statements)

References 15 publications

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“…The Rowe study [ 17 ] showed an ORR of 48.0% and a median survival time of 9.6 months, concluding that azacytidine appeared to be right WHO-AML has a good efficacy; although, IWG 2006 is not currently considered the standard form of AML efficacy assessment, but disease stabilization and HI are considered to continue to be used criteria for efficacy of azacytidine and B-cell lymphoma/leukemia-2 inhibitor therapy. In this paper, the ORR was 72.0% after 2 courses and 77.8% after 4 courses, indicating that the effective rate of patients increased with the prolongation of the treatment cycle, which is consistent with foreign related studies [ 18 ]. Azacytidine and B-cell lymphoma/leukemia-2 inhibitors' long-term chemotherapy can significantly improve patient survival outcomes.…”

Section: Discussionsupporting

confidence: 90%

“…Computational and Mathematical Methods in Medicine for efficacy of azacytidine and B-cell lymphoma/leukemia-2 inhibitor therapy. In this paper, the ORR was 72.0% after 2 courses and 77.8% after 4 courses, indicating that the effective rate of patients increased with the prolongation of the treatment cycle, which is consistent with foreign related studies [18]. Azacytidine and B-cell lymphoma/leukemia-2 inhibitors' long-term chemotherapy can significantly improve patient survival outcomes.…”

Section: Discussionsupporting

confidence: 88%

“…Subsequent studies have found that azacytidine and B-cell lymphoma/leukemia-2 inhibitors have other anticancer effects in addition to direct cytotoxicity, the most notable of which include targeting DNA hypermethylation, which is thought to help inhibit tumorigenesis and disrupt the maturation and differentiation of bone marrow cells [ 17 ]. In the pharmacokinetic study of azacytidine and B-cell lymphoma/leukemia-2 inhibitors, since the drug is only effective in proliferating cells and does not accumulate, a shorter treatment time per week is unlikely to cause azacytidine and B-cell lymphoma/leukemia-2 inhibitors to encounter at S Phase of all malignant cloned cells, which will demonstrate a higher efficacy with longer treatment per cycle [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Based on disease typing analysis, MDS-EB-1 was 4 cases, ORR was 75.0% (3/4), CR was 1 case, mCR was 2 cases, and accompaniment was HI1. In one case, the median survival time was 11.5 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) months for 1 case with disease stabilization, the MDS-EB-2 was 8 cases, the ORR was 62.5% (5/8), and the mCR was 5. In 3 cases, the disease was stable, and the median survival time was 6.5 (3 to 19) months.…”

Section: 2mentioning

confidence: 97%

“…1 case of CR, 3 cases of mCR, 1 case with HI, and 1 case of stable disease were as follows. As of February 1, 2021, the above median survival times were 13 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), 11 (8.5-22), and 13 (8.5-22) months, respectively. There were 9 cases of MDS comutation, ORR was 55.5% (5/ 9), CR was 1 case, mCR was 4 cases, with HI 1 patient, disease stable 4 patients, median survival time > AML comorbid mutation 5 patients, ORR of 60.0% (3/5), mCR 3 patients with 1 case of HI, and 2 cases of treatment failure, and the median survival time was 13 (3-14) months, see Table 3.…”

Section: Gene Mutations Of Azacytidine and B-cell Lymphoma/mentioning

confidence: 98%

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Research Progress of B-Cell Lymphoma/Leukemia-2 Inhibitor Combined with Azacytidine in the Targeted Therapy of Acute Myeloid Leukemia

Wang¹,

Huang²,

Liu³

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To investigate the efficacy and safety of azacytidine and B-cell lymphoma/leukemia-2 inhibitors in the treatment of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods. The clinical data of 31 patients with AML/MDS who were clearly diagnosed with AML/MDS were analyzed from 2018.10 to 2021.02, and the total amount of azacyclonol and B-cell lymphoma/leukemia-2 inhibitor was used for single or combined chemotherapy, with a total amount of 75 mg/m2 ∗ 7 d, divided into 7-10 days of continuous subcutaneous injection, every 28-30 days for a course of treatment. Overall response rate (ORR), median survival, poor response, and genetic mutations were observed. Results. A total of 104 courses of treatment were completed in 31 patients, the median course was 3 (1–12), and 6 patients who did not complete 2 courses of treatment were not counted in the statistics. After 2 courses, ORR was 72.0%, CRES was 2 (8.0%), mCR was 16 (64.0%), disease stable was 5 (20.0%), treatment failures were 2 (8.0%), mortality was 40.0%, and median survival time was >5 months. Single-agent and combined ORR was 64.3% and 81.8%, respectively, with median survival of 7.25 and 9 months; ORR for MDS and AML was 66.7% and 76.9%, respectively, median survival of 8 and 11 months was 66.7% and 80.0% of ORRs at 260 and V60 years, respectively, and median survival of 7 and 11.5 months; MDS-EB-1. The ORR of MDS-EB-2 was 75.0% and 62.5%, respectively, with median survival times of 11.5 and 6.5 months. During 2 courses and 4 courses, the rate of transfusion dependence was 64.0% and 55.5%, respectively. Fifteen cases were detected by second-generation sequencing, and the results were 14 cases of combined gene mutations. Conclusion. Azacytidine and B-cell lymphoma/leukemia-2 inhibitors have good efficacy and high safety in the treatment of AML and MDS, and the combined treatment is better than that of monotherapy, but the side effects of combination therapy are large.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: 2mentioning

confidence: 97%

Section: Gene Mutations Of Azacytidine and B-cell Lymphoma/mentioning

confidence: 98%

See 3 more Smart Citations

Research Progress of B-Cell Lymphoma/Leukemia-2 Inhibitor Combined with Azacytidine in the Targeted Therapy of Acute Myeloid Leukemia

Wang¹,

Huang²,

Liu³

et al. 2022

Computational and Mathematical Methods in Medicine

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Dabrafenib

2022

Reactions Weekly

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Success of Trametinib in the Treatment of Langerhans Cell Histiocytosis With Novel MAPK Pathway Mutations

Orr

Hustak

Beaudoin

et al. 2022

Journal of Pediatric Hematology/Oncology

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Approximately a third of patients with Langerhans cell histiocytosis (LCH) experience recurrence of disease. Genomic analysis has revealed that this condition is often driven by oncogenic mutations in the MAP kinase (MAPK) pathway, and agents that target components of this pathway have been explored as a second-line treatment for LCH. Here, we examine 2 pediatric patients with LCH and confirmed but rarely reported MAPK pathway mutations treated with trametinib, a MAP2K inhibitor approved to treat several cancers with a BRAF V600E mutation. Each patient achieved or maintained complete resolution of disease and remain on the drug with no adverse effects.

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Development of BRAFV600E-positive acute myeloid leukemia in a patient on long-term dabrafenib for multisystem LCH

Cited by 8 publications

References 15 publications

Research Progress of B-Cell Lymphoma/Leukemia-2 Inhibitor Combined with Azacytidine in the Targeted Therapy of Acute Myeloid Leukemia

Research Progress of B-Cell Lymphoma/Leukemia-2 Inhibitor Combined with Azacytidine in the Targeted Therapy of Acute Myeloid Leukemia

Dabrafenib

Success of Trametinib in the Treatment of Langerhans Cell Histiocytosis With Novel MAPK Pathway Mutations

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