How Does Tamibarotene Help RARA-Overexpressed MDS & AML?

During the 27th Annual Acute Leukemia Forum (April 4-5th, 2024, San Diego), Dr. Amy DeZern shared how the medicine tamibarotene is helping high-risk MDS and AML patients with an overexpressed RARA gene in their cancer cells. 

What is the Retinoic Acid Receptor Alpha Gene (RARA) in MDS and AML? 

The retinoic acid receptor alpha gene, or RARA, plays a significant role in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The RARA gene codes for a receptor that helps cells, like myeloblasts, develop into their mature forms, becoming basophils, neutrophils, eosinophils, or monocytes. Myeloblasts are the cells affected by MDS and AML. 

When the RARA gene is overexpressed, it produces too many receptors and can disrupt the cell differentiation process. This disruption can lead to improper blood cell development, contributing to the symptoms and progression of MDS and AML. 

About 50% of high-risk MDS and 30% of AML patients test positive for RARA gene overexpression. 

How is RARA Gene Overexpression Tested for MDS and AML? 

A blood test evaluates whether a patient has an overexpressed RARA gene in their MDS or AML cells. The test involves drawing a blood sample and sending it to a lab, where it is processed and evaluated for RARA gene overexpression. The test results come back within 2-3 days. RARA+ means that the patient has an overexpressed RARA gene. RARA- means the patient does not have an overexpressed RARA gene. 

What is Tamibarotene? 

Tamibarotene, a pill taken by mouth, is a synthetic form of retinoid derived from vitamin A. Doctors found that after treating RARA-overexpressed MDS and AML patients with tamibarotene, myeloblasts in the bone marrow were reduced, and normal cell differentiation levels were restored. 

Tamibarotene was also reported to be more potent at reducing cancer cells when combined with the hypomethylating agent azacitidine (Vidaza). 

Is Tamibarotene FDA-Approved for MDS & AML? 

The treatment combination of tamibarotene, azacitidine, and venetoclax for RARA-overexpressed AML was granted FDA fast-track designation in April 2024. FDA fast-track designation is a program that accelerates developing and reviewing medicines intended to treat serious conditions and address unmet medical needs. 

Tamibarotene was granted FDA fast-track designation in 2023 for treating higher-risk, RARA-overexpressed MDS. 

Tamibarotene in combination with azacitidine is being reviewed in a clinical trial for higher-risk, RARA-overexpressed MDS patients. Click here to learn more about the trial. If you need help signing up for the study, click “Begin Now” for HealthTree Patient Navigators to assist you. 

In conclusion, tamibarotene effectively reduces myeloblasts and restores cell differentiation in RARA-overexpressed MDS and AML. This treatment may provide further hope to patients with RARA-overexpression in their cancer cells. 

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Sources 

• Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist 
• RARA Pathway Activation Biomarkers in Study SY-1425-201 Define a New Subset of AML and MDS Patients and Correlate with Myeloid Differentiation Following Ex Vivo SY-1425 Treatment
• A randomized, double-blind, placebo-controlled study of tamibarotene/azacitidine versus placebo/azacitidine in newly diagnosed adult patients selected for RARA+ HR-MDS (SELECT-MDS-1)
• Early Results from a Biomarker-Directed Phase 2 Trial of Sy-1425 in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Demonstrate DHRS3 Induction and Myeloid Differentiation Following Sy-1425 Treatment 
• Syros Receives Fast Track Designation from the FDA for Tamibarotene for the Treatment of Newly Diagnosed Unfit AML with RARA Gene Overexpression
• Syros Receives Fast Track Designation from the FDA for Tamibarotene for the Treatment of Higher-Risk Myelodysplastic Syndrome