FDA Approves New All-Oral Treatment for Acute Myeloid Leukemia in Older and Medically Fragile Adults

The U.S. Food and Drug Administration (FDA) has given the green light to a new all-oral treatment regimen for people newly diagnosed with acute myeloid leukemia (AML) who cannot handle strong chemotherapy. The approval, announced on Wednesday, combines two pills: decitabine-cedazuridine (brand name Inqovi) and venetoclax (Venclexta). This option is designed for adults aged 75 and older, as well as those who have other health problems that make intensive induction chemotherapy too dangerous. Together, these groups represent more than half of the 20,000-plus AML diagnoses made each year in the United States.

Understanding Acute Myeloid Leukemia and Why Some Patients Cannot Have Standard Treatment

Acute myeloid leukemia is a fast-growing cancer of the blood and bone marrow. In a healthy body, bone marrow creates normal white blood cells, red blood cells, and platelets. In AML, the marrow makes abnormal cells that multiply quickly and crowd out healthy ones. Standard treatment for younger, fit adults often involves intensive induction chemotherapy. This powerful treatment uses very high doses of medicine given through an IV over several days, usually requiring a long hospital stay. The goal is to wipe out leukemia cells and achieve a remission, meaning no signs of cancer remain.

However, many people diagnosed with AML are older. The average age at diagnosis is close to 70. Aging bodies and the presence of other medical conditions—such as heart disease, kidney problems, or lung issues—can make intense chemotherapy far too risky. Potent chemo can cause life-threatening infections, severe organ damage, or a long and difficult recovery. For these patients, doctors have historically used milder treatments, often lower doses of chemotherapy or hypomethylating agents like decitabine or azacitidine given by injection or IV. While gentler, these approaches often led to fewer complete remissions. The challenge has always been to find a balance: enough power to fight the cancer without causing serious harm to the patient.

A Shift Toward Oral Cancer Care

One recent bright spot has been the addition of a targeted pill called venetoclax. This drug blocks a protein that helps leukemia cells survive. When paired with an IV or injected hypomethylating agent, venetoclax has become a standard choice for newly diagnosed older or unfit AML patients. But that regimen still required regular trips to a clinic or hospital for the IV drug—a burden for elderly patients and their families.

The new approval changes the game by making the backbone therapy an oral pill rather than an infusion. Inqovi itself is a fixed-dose combination tablet that contains decitabine plus cedazuridine. Cedazuridine stops the body from breaking down decitabine too quickly in the gut, allowing the cancer-fighting medicine to reach the bloodstream in effective amounts despite being swallowed instead of injected. The FDA first approved Inqovi in 2020 for certain bone marrow disorders called myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Now, pairing it with oral venetoclax creates a completely all-oral, at-home option for untreated AML patients who cannot have intensive chemo.

What the Clinical Trials Revealed

The FDA based its approval of this specific combination on a clinical trial called ASCERTAIN-V. The study was open-label and single-arm, meaning everyone knew what treatment they were receiving and there was no placebo group. It included 101 adult participants who were unable to undergo intensive induction chemotherapy. After taking the decitabine-cedazuridine and venetoclax regimen, 41.6% of patients achieved a complete remission (CR). Complete remission means no detectable leukemia cells using standard testing. The duration of those complete remissions ranged from 0.5 to 16.3 months, and the median (midpoint) had not been reached at the time of analysis. The median time to a complete remission was 2 months.

Separately, another phase II study conducted in a similar patient population looked at the same all-oral combination. That trial reported a 64% overall response rate. Within that group, 57% reached either a complete remission or a complete remission with incomplete recovery of blood counts (sometimes called CRi). Among those who achieved a CR or CRi, the median duration of response was 13.2 months. These numbers offer meaningful hope to a group of patients who previously had few effective and convenient options.

Safety Information and Side Effects to Know

As with any cancer treatment, this regimen comes with important risks. The drug labeling lists side effects that occurred in 20% or more of patients during studies. These include several serious conditions that need careful monitoring and quick medical attention. Because the treatment powerfully affects the bone marrow, blood counts often drop, raising the chance of infection, bleeding, and fatigue.

Common Side Effects (Seen in 20% or More of Patients)

• Neutropenia (very low white blood cell count)
• Febrile neutropenia (low white blood cells with fever)
• Thrombocytopenia (low platelets)
• Hemorrhage (bleeding)
• Anemia (low red blood cells)
• Bacterial infections
• Viral infections
• Diarrhea
• Fatigue
• Mucositis (mouth sores)
• Constipation
• Joint pain (arthralgia)
• Decreased appetite
• Edema (swelling from fluid buildup)
• Nausea
• Shortness of breath (dyspnea)
• Decreased white blood cell counts
• Sepsis (body’s extreme response to infection)
• Pneumonia
• Rash
• Transaminitis (elevated liver enzymes)
• Muscle pain (myalgia)
• Arrhythmia (irregular heartbeat)
• Abdominal pain

Severe Lab Changes and Serious Health Events

Common grade 3 or 4 laboratory abnormalities—meaning the lab values are severe enough to need medical attention—included drops in leukocytes, lymphocytes, platelets, and hemoglobin. These are often managed with transfusions, growth factor medications, or antibiotics.

Serious adverse events affected 82% of patients in the trial. The table below shows how frequently some of these severe reactions occurred:

• Febrile neutropenia – 31%
• Sepsis – 22%
• Pneumonia – 15%
• Other infections – 10%
• Hemorrhage – 9%
• Shortness of breath (dyspnea) – 6%

Fatal adverse events, meaning deaths that were considered related to treatment, happened in 8% of patients. The prescribing information also carries strong warnings about myelosuppression (dangerously lowered bone marrow activity) and embryo-fetal toxicity, which means the drugs can harm an unborn baby. People

Source: MedPage Today