Hairy Cell Leukemia Treatment Approved

The FDA has approved moxetumomab pasudotox-tdfk (Lumoxiti; AstraZeneca) to treat patients with relapsed/refractory hairy cell leukemia (HCL) who have not responded to at least two prior treatments, including a purine nucleoside analogue.

The drug, the first CD22-directed recombinant immunotoxin to be greenlighted for HCL, consists of a portion of the anti-CD22 antibody connected to a cytotoxic payload containing a fragment of Pseudomonas exotoxin-A. The FDA previously approved the CD22-directed recombinant immunotoxin inotuzumab ozogamicin (Besponsa; Pfizer) to treat some types of B-cell acute lymphoblastic leukemia.

The approval of moxetumomab pasudotox-tdfk was based on results of a single-arm, open-label trial of 80 patients treated with the drug: 41% had a complete response and 30% had a complete response lasting at least 180 days; the objective response rate was 75%.

“It's surprising and wonderful that there is an approval in such a rare disease,” says James Blachly, MD, of The Ohio State University Comprehensive Cancer Center in Columbus. “It's a disease that a lot of people consider cured or solved, but for those people who continue to relapse or have very bad disease, this approval matters a great deal.” Moxetumomab pasudotox-tdfk is the first drug in more than 20 years to receive FDA approval for HCL.

Blachly adds that HCL is one of the rarest leukemias, with only 900 to 1,200 new cases in the United States every year. Most patients experience a durable response to the purine nucleoside analogues pentostatin (Nipent; SuperGen) or cladribine. However, 30% to 40% of patients relapse 5 to 10 years after their first treatment, often due to minimal residual disease. Moreover, Blachly says that patients tend to achieve shorter and shorter remissions with each successive round of treatment, and repeated courses of purine nucleoside analogues can lead to immunosuppression or secondary cancers.

“It's unclear yet whether moxetumomab pasudotox-tdfk will be reserved only for the worst of the worst, or if we'll find that instead of repeating purine nucleoside analogues, that we can give this and be done,” Blachly says. He notes that although the new drug can cause a side effect called capillary leak syndrome, characterized by a dangerous drop in blood pressure, evidence suggests that the drug may eliminate all traces of the disease, giving it “the potential to produce a very deep and lasting remission.”

“It will be interesting to see how this approval shapes the treatment landscape of relapsed/refractory hairy cell leukemia going forward,” he says. –Catherine Caruso