FDA Approves 2 Treatments in Older Adults With Newly Diagnosed AML

Older patients diagnosed with acute myeloid leukemia (AML) who may not be able to be treated with intensive chemotherapy will now have 2 new treatment options. The FDA approved Daurismo (glasdegib from Pfizer), a once-daily oral tablet used in combination with low-dose cytarabine (LDAC), a nonintensive chemotherapy, and also approved Venclexta (venetoclax from Abbvie and Genentech) in combination with azacitidine or decitabine or LDAC.

Glasdegib and venetoclax were both approved to treat adults age 75 or older who are newly diagnosed with AML and have other chronic health conditions or diseases that may mean they cannot use intensive chemotherapy. Venetoclax was approved under accelerated approval and continued approval for this indication may be contingent upon the results of clinical benefit in confirmatory trials.

“Intensive chemotherapy is usually used to control AML, but many adults with AML are unable to have intensive chemotherapy because of its toxicities,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.

Glasdegib is a Hedgehog pathway inhibitor; studies have shown that disrupting the pathway can impair the development and survival of cancer stem cells. The treatment was approved based on the pivotal, randomized phase 2 BRIGHT 1003 trial.

The trial included 115 patients with newly diagnosed AML who were randomized 2:1 to receive glasdegib plus LDAC (n = 77) or LDAC alone (n= 38). More than half (51%, 39 patients) of the patients in the glasdegib arm had secondary AML.

According to the study findings, the median survival for patients treated with glasdegib plus LDAC was 8.3 months compared with 4.3 months for patients treated with LDAC alone. The most common (≥20% of patients) side effects for patients treated with glasdegib were anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.

“The ongoing phase 3 BRIGHT trials are evaluating Daurismo in combination with other agents commonly used to treat patients with acute myeloid leukemia, in an effort to understand the full potential of this medicine against this aggressive leukemia,” Mace Rothenberg, MD, chief development officer, oncology, Pfizer Global Product Development, said in a statement.

Venetoclax is an oral B-cell lymphoma-2 (BCL-2) inhibitor and by targeting BCL-2, the treatment restores natural death or self-destruction of cancer cells. Study M14-358 included 67 patients who received venetoclax with azacitidine and 13 patients who received venetoclax with decitabine.

The complete remission (CR) rate was 37% for the azacitidine arm and 54% for the decitabine arm. Patients who achieved CR with azacitidine had a median time in remission of 5.5 months and patients who achieved CR with decitabine had a median remission of 4.7 months.

Separately, 61 patients were enrolled in Study M14-387 to receive venetoclax with LDAC. These patients had a CR rate of 21% and the median time in remission for patients who achieved CR was 6 months.

“AML is an extremely aggressive and debilitating blood cancer, and outcomes for patients ineligible for intensive chemotherapy are very poor," Michael Severino, MD, executive vice president, research and development, and chief scientific officer, AbbVie, said in a statement. "This new approval for Venclexta marks a significant milestone for AbbVie and, more importantly, for patients diagnosed with this deadly disease.”