Le tramétinib pourrait être une option efficace pour le traitement de la JMML en rechute ou réfractaire – Hematology Advisor

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Related News COVID-19 mRNA Vaccine May Not Improve Outcomes With ICIs as Previously Reported Pregnancy May Worsen Immune Thrombocytopenia Psychotherapy May Improve Comorbid Chronic Pain and Trauma Symptoms Top Picksfrom our Haymarket Medical Network Long-Term PARP Inhibitor Maintenance may be Unnecessary in Recurrent Ovarian Cancer Long-Term PARP Inhibitor Maintenance may be Unnecessary in Recurrent Ovarian Cancer Treatment of juvenile myelomonocytic leukemia (JMML) with trametinib demonstrated promising response rates in a small phase 2 trial conducted by the Children’s Oncology Group, according to results published in the journal Cancer Discovery. The researchers also reported that a majority of patients were alive at follow-up and the 4-year overall survival was 80%. In this phase 2 ADLV1521 trial (ClinicalTrials. gov Identifier: NCT03190915), researchers treated 10 infants and children with advanced JMML with a maximum of 12 cycles of trametinib. The median age of the patients was 23.6 months (range, 10.7-78.7 months) and 8 were male. All patients had a Ras pathway mutation, including of KRAS, CBL, PTPN11, or NRAS. There were 7 patients with refractory disease at enrollment. There were 5 patients who achieved an objective response, which included 2 patients who achieved a complete response, resulting in a rate of 50%. There were 2 patients with stable disease. At a median follow-up of 24 months, all 7 of these patients were alive. There were 3 patients who completed study treatment and continued to receive trametinib off-protocol for an additional 6 or 24 months. A total of 4 of the patients with an objective response who were previously unfit for a hematopoietic stem cell transplant (HSCT) went on to undergo an HSCT after improvement in clinical status. These 4 patients were in remission at follow-up. There were 3 patients who experienced progressive disease during trametinib treatment, all of whom underwent HSCT. However, 2 of these patients died with refractory disease. One patient underwent a second HSCT and remains alive. Trametinib treatment did not change the variant allele frequency of the initial Ras pathway mutation or DNA hypermethylation in any of the patients. However, the mutation was no longer detected in 4 patients who underwent HSCT after trametinib. Pre- and post-treatment data also demonstrated that trametinib downregulated the MAPK pathway. Seven patients developed grade 3 adverse events (AEs) that the researchers considered possibly related to trametinib, which included neutropenia, anemia, viral sepsis, and hypertension. There were no reports of cardiac dysfunction. “Although limited by the small number of patients, the long-term survival and correlative molecular analyses from this trial raise provocative questions about whether certain patients with JMML might be spared the long-term adverse risks of genotoxic HSCT conditioning regimens based on favorable molecular characteristics at diagnosis, ” the researchers concluded in their report. Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures. Stieglitz E, Lee AG, Angus SP, et al. Efficacy of the allosteric MEK inhibitor trametinib in relapsed and refractory juvenile myelomonocytic leukemia: a report from the Children’s Oncology Group. Cancer Discov. Published online June 11,2024. doi: 10.1016/ S2352-3026(24)00132-7 COVID-19 mRNA Vaccine May Not Improve Outcomes With ICIs as Previously Reported Pregnancy May Worsen Immune Thrombocytopenia Psychotherapy May Improve Comorbid Chronic Pain and Trauma Symptoms Long-Term PARP Inhibitor Maintenance may be Unnecessary in Recurrent Ovarian Cancer