Abstract
The FDA's decision to approve inotuzumab ozogamicin for patients with relapsed or refractory acute lymphoblastic leukemia could open up further uses for the drug. It is being tested as a first-line treatment in combination with chemotherapy. The decision could also stimulate research into other antibody–drug conjugates.
The FDA has approved inotuzumab ozogamicin (Besponsa; Pfizer), an anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, for patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The drug has a niche in treating this group of patients, researchers say, but they predict it will be useful in a broader range of patients and will stimulate research on its drug class, antibody–drug conjugates (ADC).
Central to the FDA's decision was the phase III INO-VATE ALL trial, which compared inotuzumab ozogamicin to standard chemotherapy in 326 patients with relapsed or refractory ALL (N Engl J Med 2016;375:740–53). The complete remission rate was 80.7% in the patients who received the ADC, versus 29.4% in the chemotherapy group. The median overall survival was 7.7 months in the ADC group and 6.7 months in the chemotherapy group.
Unlike chemotherapy, antibody–drug conjugates target cancer cells and spare healthy cells. Highly stable linkers help keep the drug from falling off in circulation, thus enabling it to reach cancer cells.
Blinatumomab (Blincyto; Amgen) is also an option for patients with relapsed or refractory B-cell precursor ALL, and the chimeric antigen receptor T-cell therapy tisagenlecleucel (Kymriah, CTL019; Novartis) was approved on August 30. However, inotuzumab ozogamicin stands out, says Daniel DeAngelo, MD, PhD, of Dana-Farber Cancer Institute in Boston, MA, given the impressive 80% remission rate in the phase III trial. “I do think this is going to mean a huge improvement in outcome for our patients,” he says.
The drug has other advantages as well, says Nakhle Saba, MD, of Tulane University School of Medicine in New Orleans, LA. In the INO-VATE ALL trial, 41% of the patients treated with inotuzumab ozogamicin were able to proceed to allogenic stem cell transplantation, whereas only 11% of the patients who received chemotherapy were.
Clinical trials are testing the drug in other patient groups. For example, a phase III trial is evaluating the combination of inotuzumab ozogamicin and chemotherapy as a first-line treatment for people between the ages of 18 and 39 years diagnosed with ALL.
Researchers say the FDA's decision might also stimulate research into ADCs. These drugs use an antibody to deliver a toxic chemical specifically to cancer cells and differ from drugs such as rituximab, in which the antibody itself is therapeutic. The first ADC approved, the anti-CD33 monoclonal antibody gemtuzumab ozogamicin (Mylotarg; Pfizer) for acute myeloid leukemia (AML), was pulled from the market in 2010 due to safety and efficacy concerns—although the FDA reapproved it on September 1 for a different group of patients with AML.
Christoph Rader, PhD, of The Scripps Research Institute in Jupiter, FL, notes that the drug's withdrawal, along with problems with other ADCs in clinical trials, dampened pharmaceutical companies' interest in the drugs. Inotuzumab ozogamicin is only the third ADC to receive FDA approval for cancer treatment since 2010, whereas 15 other antibody-based cancer treatments have reached the market during that time. The FDA's decision on inotuzumab ozogamicin “gives the field a boost,” he says. –Mitch Leslie
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