Precision Medicine Revives Leukemia Drug

Gemtuzumab ozogamicin observed to benefit subset of patients with acute myeloid leukemia.

Gemtuzumab ozogamicin (Mylotarg) was the first immunotherapy to receive regulatory approval; however, after being on the market for 10 years, the FDA found that the drug did not add a survival benefit for patients with leukemia. Gemtuzumab ozogamicin was subsequently withdrawn from the market.

However, new research published by the Journal of Clinical Oncology suggests that the drug may actually be beneficial for a certain group of patients with acute myeloid leukemia (AML).

“Our search for one drug that cures everything is really misplaced,” said senior author Soheil Meshinchi, MD, PhD. “The drugs that failed in the past, [it] may not have been the drug’s failure but our failure to match them to the appropriate target.”

Gemtuzumab ozogamicin binds to the CD33 molecule, which is found on the surface of leukemia cells. The cancer cell then consumes the drug and is eliminated.

The authors discovered that approximately 50% of patients had a single-letter change in a particular spot in their DNA code, according to the study. While this is generally not an important finding, this change resulted in the creation of CD33 proteins that could not bind to gemtuzumab ozogamicin, thus making it ineffective.

This occurrence was found to identify gaps in patient outcomes during clinical testing. The authors found that patients without the binding site did not have a reduced risk of relapse due to treatment with gemtuzumab ozogamicin.

Of patients whose binding site was intact, those administered chemotherapy only had a 49% risk of relapse, while patients who also received gemtuzumab ozogamicin had a 26% risk of relapse, according to the study.

Similar results were observed related to disease-free survival.

“This is really amazing,” Dr Lamba said. “I think the results are pretty convincing, and we should use them to make much better calls [about treatment] for the benefit of the patients.”

The investigators believe that these findings could also have implications for other drugs that target CD33. These findings could revive the use of gemtuzumab ozogamicin for patients with AML who have certain changes in their DNA.

Additionally, the difference between the response of the patient groups was much more significant than what researchers typically find, according to the study.

“In AML, our clinical trials are designed hoping to detect a 6% to 8%difference in outcome [between patient groups],” Dr Meshinchi concluded. “If we get an 8% improvement in survival for AML that’s a home run. That tells you how difficult a disease this is to cure. So, this is as big a home run as you could possibly have in AML.”