CAR T-Cell Therapy for Relapsed Hairy Cell Leukemia

Dr. Robert J. Kreitman of the National Cancer Institute has spent more than three decades working on hairy cell leukemia (HCL). He first encountered the disease in 1983 as a medical resident under Dr. Bertha Bouroncle, who first described it. In 1989, working with Dr. Ira Pastan at the NCI, he found that HCL patients responded especially well to an experimental immunotoxin. That work led to BL22 and then to moxetumomab pasudotox (Lumoxiti), which was developed in their lab and approved by the FDA for relapsed and refractory HCL. The manufacturer later withdrew the drug, and efforts are underway to bring it back.

Today, Dr. Kreitman’s focus includes a CAR T-cell trial targeting CD22, a protein found in high amounts on hairy cells. Patients in the trial are heavily pretreated. They have received cladribine, pentostatin, rituximab and BRAF inhibitors, and in some cases splenectomy.

He describes CAR T and Lumoxiti as complementary. Lumoxiti works best when patients have many leukemia cells in the blood and enlarged spleens, while CAR T works best against solid masses of disease. In patients with very high blood counts, CAR T can cause serious toxicity, including fever and cytokine release. Neurologic side effects seen with other cancers have not been observed in HCL.

One patient had extensive prior treatment and a mass that blocked drainage from his kidney. He has now shown no trace of HCL for more than two and a half years after CAR T. Dr. Kreitman says it could be a cure, and he urges patients to consider CAR T before their disease becomes too advanced.

Asked whether HCL can be cured, he answers, “We think it can be.” One patient treated with BL22 more than 25 years ago still shows no detectable disease. The key, he says, is eliminating minimal residual disease, which otherwise leads to relapse.

He stresses that CAR T is “not as bad as people think.” Unlike a transplant, it uses the patient’s own cells, with no risk of graft-versus-host disease.

Looking ahead, Dr. Kreitman hopes these treatments will win FDA approval so doctors can offer them to more patients with HCL.

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