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Is revumenib a boon for acute myeloid leukemia patients??

The most prevalent form of leukemia in adults is acute myeloid leukemia (AML), which makes up around 80% of all the cases. The significant features of this condition are the appearance of immature blast cells in the peripheral blood and bone marrow caused by ineffective erythropoiesis and bone marrow failure. The cure rates have increased by up to 15% in patients over 60 years of age and by about 40% in individuals under 60 years, as a result of recent improvements in management guidelines [1].


What is the prognosis for Aml?


  • The majority of patients are still diagnosed at an advanced stage despite advances in diagnostics and therapies, and the prognosis has still not improved much, especially in the older population.

  • Moreover, the first-line medications that are now available for the advanced stage of the disease remain ineffective in terms of efficacy.

  • Chemotherapy is the first line therapy for AML patients. Drugs like cytarabine, daunorubicin, fludarabine, mitoxantrone, etoposide, and 6-thioguanine are commonly used. But they are associated with several side effects like vomiting, diarrhea, reduced blood cell counts, and recurrent infections.

  • Radiotherapy alone before chemotherapy or combination of chemo and radiotherapy can be used to increase the effectiveness of chemotherapy in refractory or relapsed cases.

  • Immunotherapy and targeted therapy have recently become promising therapeutic options for AML. They can be given in relapsed or refractory cases where conventional treatment fails. Commonly used immunotherapeutic drugs are monalizumab, monoclonal antibodies ,CAR T-cell therapy, and targeted therapy drugs are ivosidenib, enasidenib, olutasidenib, midostaurin, gilteritinib, and gemtuzumab [1].


What is revumenib?


  • AML, one of the most challenging leukemia to treat, may benefit from a novel type of targeted therapeutic drug called revumenib, that was recently introduced. Revumenib(SNDX-5613) belongs to the group of menin inhibitors and is a type of oral precision cancer medication [2].

  • The FDA (Food and Drug administration) and the European Commission designated revumenib as an orphan drug for the treatment of AML patients.

  • Also, it has been given fast track designation by the FDA, for the treatment of adult and pediatric patients with advanced acute leukemia with mutation.

  • When administered to patients with advanced acute myeloid or lymphoid leukemia, revumenib is hypothesized to impede the interaction between menin and (mixed lineage leukemia) protein.

  • Both of these proteins interact with each other in a way resulting in the formation of a complex that activates particular genes necessary for the growth of leukemia cells [3].


What is the clinical efficacy of revumenib in aml?


Because preliminary clinical studies have demonstrated that revumenib is beneficial in treating AML, it has been examined in greater depth in clinical settings. Clinical studies are now being conducted to see whether it can enhance AML's prognosis particularly in refractory cases. The clinical studies being conducted for revumenib include the ones listed below:


  • Revumenib (SNDX-5613) showed persistent effectiveness in a phase III randomized controlled trial called AUGMENT-101 (ClinicalTrials.gov identifier -NCT04065399). Revumenib shows acceptable safety in patients with refractory or relapsed AML cases with MLL gene rearrangement [4].

  • Another phase III trial was conducted to evaluate the effectiveness of revumenib, when combined with chemotherapy in refractory or relapsed leukemia cases (ClinicalTrials.gov identifier - NCT05761171). This trial helps us to know if the combination of revumenib along with chemotherapy may help to treat the cancer cells better than either treatment alone [5].


Future directions!


According to the literature, revumenib holds tremendous potential as a revolutionizing treatment for AML patients. However, additional investigation is required to confirm its effectiveness and safety in clinical settings. To determine whether these menin inhibitors can enhance the clinical outcomes for individuals with refractory acute leukemia or not, the outcomes of ongoing clinical trials examining revumenib are eagerly anticipated.


References


1. A. Vakiti and P. Mewawalla, Acute Myeloid Leukemia,” in StatPearls, Treasure Island (FL): StatPearls Publishing, 2023. Accessed: Jun. 26, 2023. [Online]. Available: http://www.ncbi.nlm.nih.gov/books/NBK507875/

2. A. Fareed, N. Inam, and F. Faraz, Breakthrough treatment choice for Acute Myeloid Leukemia in pediatric and adult patients: Revumenib, an oral selective inhibitor of KMTA2Ar,Rare Tumors, vol. 15, p. 20363613231183784, Jun. 2023, doi: 10.1177/20363613231183785.

3. Revumenib Shows Promise for Advanced Acute Myeloid Leukemia - NCI,” Apr. 18, 2023. https://www.cancer.gov/news-events/cancer-currents-blog/2023/revumenib-menin-inhibitor-advanced-aml (accessed Jun. 20, 2023).

4. A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation - Full Text View - ClinicalTrials.gov.” https://clinicaltrials.gov/ct2/show/NCT04065399 (accessed Jun. 26, 2023).

5. “A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia - Full Text View - ClinicalTrials.gov.” https://clinicaltrials.gov/ct2/show/NCT05761171 (accessed Jun. 26, 2023).

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