Combination therapy effective for higher-risk MDS/AML patients

A phase two study investigating the potential of the drugs azacitidine (AZA) and lenalidomide (LEN), demonstrated that the two therapies in combination may be an effective front-line treatment for patients with higher-risk forms of myelodysplastic syndrome and acute myeloid leukemia.

Myelodysplastic syndrome (MDS) is a type of cancer in which the bone marrow does not make enough healthy blood cells, resulting in abnormal (blast) cells in the blood and/or bone marrow. Higher-risk patients experience an unusually large percentage of blasts in their blood. Patients often develop infections, anemia, or excessive bleeding. Acute myeloid leukemia (AML) is a blood cell cancer and is the most common acute leukemia affecting adults, with incidences increasing with age.

The study, led by Guillermo Garcia-Manero, M.D., professor of Leukemia at MD Anderson Cancer Center, shed new light on effective dosage schedule and amounts for the drugs, something previously unknown. The combination therapy was well tolerated in the study of 88 patients.

The study results were presented recently by Courtney Dinardo, M.D., assistant professor of Leukemia, at the 56th Annual Meeting of the American Society of Hematology (ASH) annual conference in San Francisco and were published in the journal Blood.

“Hypomethylating (HMA) agents such as AZA and LEN are currently the front line of therapeutic choice for patients with higher-risk MDS, and also frequently used in elderly AML patients not otherwise eligible for standard intensive therapy,” said DiNardo. “A number of combination strategies are under development to improve the results of HMA therapy. Given what we know about the effectiveness of AZA and LEN in patients with MDS and AML, a scientific rationale existed to explore this therapeutic combination strategy.”

DiNardo's team evaluated the administration of AZA and LEN on days 6 to 10 of a 28-day cycle of treatment. The combination therapy appeared to be effective in patients presenting with as high as 30 percent blasts or abnormal blood/bone marrow cells.

“The responses were rapid with a median of two cycles for the drugs to be effective. Treatment with this dosage and schedule was well tolerated,” said DiNardo.

Combo of cytarabine and vosaroxin benefit AML patients who face relapse

Patients who relapse in their battle with acute myeloid leukemia (AML) may benefit from a phase three study of therapies that combine an existing agent, cytarabine, with a newer compound, vosaroxin.

The study, led by Farhad Ravandi, M.D., professor of medicine, department of Leukemia at MD Anderson Cancer Center, demonstrated increased survival rates, particularly in AML patients over age 60.

Ravandi’s study results were presented recently at the 56th Annual Meeting of the American Society of Hematology (ASH) annual conference in San Francisco and were published in the ASH journal Blood.

Acute myeloid leukemia is the most common form of adult leukemia. The current accepted treatment, cytarabine, when used with other existing agents such as anthracyclines, is associated with increased toxic side effects.

The 124-site international randomized trial was among the largest of its kind. It demonstrated that combination therapy employing the agent cytarabine with others such as vosaroxin does not cause the significant toxic side effects experienced when cytarabine is used in combination with anthracyclines.

“Currently there are no standard-of-care approved treatments for relapsed or treatment-resistant AML. Effective and safe therapies are critically needed for patients with relapsed or treatment-resistant acute myeloid leukemia” said Ravandi. “These data provide encouraging support that this combination may be an effective new salvage therapy in older patients with this challenging condition.”

Toxic side effects from combining cytarabine with anthracyclines or topoisomerase inhibitors can include damage to the heart muscle. By combining cytarabine with new agents, researchers hope to develop an effective treatment for AML that does not cause significant additional toxicity. One such agent is vosaroxin, an agent that can target and evade the cancer cell’s natural defenses and help induce cancer cell death. Researchers have investigated this compound in a phase three randomized trial to evaluate its ability to overcome the limitations of current therapies without the cardiotoxicities commonly observed with other treatments.

In the trial, 711 patients with relapsed or hard-to-treat AML at 124 sites worldwide were randomized to receive cytarabine with either vosaroxin or placebo. Patients treated with vosaroxin achieved longer overall survival compared to those treated with placebo (7.5 months versus 6.1 months) and were more likely to achieve complete response or remission (30.1% experiencing complete response in the vosaroxin arm versus 16.3% in the placebo arm).

Significantly, patients age 60 or older and those experiencing early relapse had the greatest overall survival benefit from the treatment. Early mortality was similar in the two arms, and the most common adverse events were neutropenia or low white-blood-cell levels, sepsis, infections and mouth sores.