CAR T Cells Drive CLL Remissions

Chimeric antigen receptor (CAR) T cells are on the verge of receiving FDA approval to treat some patients with acute lymphocytic leukemia (ALL). A phase I/II trial now suggests they are also effective in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

CAR T cells have shown promise against several blood malignancies. Last month, an FDA advisory panel recommended approval of the CAR T-cell therapy CTL019 (Novartis) for children and young adults with B-cell ALL. Earlier this year, a similar treatment from Kite Pharma, KTE-C19, produced positive results in non-Hodgkin lymphoma. Although a few trials have tested CAR T-cell therapy for CLL, they were small and didn't evaluate whether the treatment is useful for patients with relapsed or refractory disease. “We have great drugs for CLL, but when patients fail these treatments they have very few options,” says study co-author David Maloney, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, WA.

In the study, 24 patients with CLL underwent CAR T-cell therapy after their disease progressed despite receiving ibrutinib (Imbruvica; Johnson & Johnson), a standard therapy for the disease, or because they were unable to tolerate the drug. The researchers used CAR T cells developed at Fred Hutchinson Cancer Research Center that, like the Novartis and Kite products, target CD19 on cancer cells.

Most patients developed adverse effects from the treatment. Twenty developed cytokine release syndrome, characterized by symptoms such as fever and low blood pressure; six required treatment. Neurologic symptoms occurred in eight patients, one of whom died as a result.

However, most patients also benefitted from the therapy. The objective response rate (ORR), which the team gauged 4 weeks after infusion of the CAR T cells, was 71%. The median progression-free survival was 8.5 months; median overall survival hadn't been reached. The treatment seemed to be better at eliminating disease from the bone marrow than from the lymph nodes. Maloney and colleagues determined that cancer cells were undetectable in the bone marrow in 81% of the patients they tested who had bone marrow involvement before therapy. PET scans showed complete responses in the lymph nodes in 64% of the tested patients.

The trial suggests that “these cells could be effective in clearing the disease, even in patients with a poor prognosis,” says Maloney. He notes that the cells' lower effectiveness against lymph node disease may require physicians to select patients for therapy earlier, before they've developed large lymph node masses.

Researchers not connected to the trial are enthusiastic about the results. “A 71% ORR is definitely promising,” says Nathan Singh, MD, of the University of Pennsylvania in Philadelphia. Other scientists say the findings could alter clinical practice. “This could be a paradigm-changing therapy for CLL,” says Elizabeth Shpall, MD, of The University of Texas MD Anderson Cancer Center in Houston.

The researchers tracked the therapy's recipients for only a median of 6.6 months, cautions Chadi Nabhan, MD, of Cardinal Health in Dublin, OH, so “the next step is to continue following up on these patients.” So far, however, “I would say that the results are very impressive, given the difficult and refractory patient population being studied.”

Maloney says that he and his colleagues continue to track the patients from the study and are planning a phase II, multicenter trial with other researchers to confirm the results. –Mitch Leslie