Novel CD22 CAR-T Works After CD19 Product Failed

Nancy A. Melville

June 18, 2018

STOCKHOLM, Sweden — A novel CD22-directed chimeric antigen receptor T-cell (22-CAR-T) therapy has shown  efficacy and safety in the treatment of refractory or relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL) in pediatric patients in whom CD19 CAR T-cell therapy previously failed and who have otherwise particularly poor prognoses.

"22-CAR-T-cell immunotherapy brings hope for the patients with r/r B-ALL who failed on CD19-CAR T therapy," said first author Jing Pan, MD, associate director of the  Department of Hematology at Beijing Boren Hospital, China, in presenting the research here at the European Hematology Association (EHA) 2018 Congress.

Pan and her team had previously reported on efficacy of low-dose CD19 CAR T cell therapy in r/r B-ALL in research published last year in the journal Leukemia. However, as that study showed, disease progression within 1 year is common, and once they relapse, patients are resistant to a secondary CD19 CAR T-cell therapy because of the loss or mutation of CD19.

Thus, Pan and  colleagues turned to another target, CD22, which is highly expressed in leukemia in patients with r/r B-ALL.

For the study, 15 pediatric patients were recruited at Beijing Boren Hospital; their median age was 8 (range, 2 - 19) years, and the median disease course was 21 (range, 5 - 84) months.

All patients showed expression of CD22 leukemia cells, and 14 of the 15 patients had previously been treated with CD19 CAR T-cell therapy. Four patients had relapsed after allogeneic hematopoietic stem cell transplantation (allo-HCT) and 11 had relapsed after chemotherapy.

By using a lentiviral vector, a second-generation CAR with anti-CD22 properties was developed from a humanized CD22 antibody, and the manufacturing of the CD22 CAR T cells was completed in 7 to 8 days.

With median doses of 22-CAR-T infusions of 8.2 (range, 0.5 - 34.7) × 105/kg in patients who had not received allo-HCT and 0.9 (range, 0.7 - 5.0) × 105/kg in patients who had received allo-HCT, the peak expansion of the cells was seen at day 11.

On day 30 after infusion, 86.7% (13 of 15) of patients had a response, with 10 of 11 patients with hematologic relapse achieving a complete remission or a complete remission with incomplete count recovery.

Two of the patients showed minimal residual disease (MRD) positivity by flow cytometry.

By day 50, 11 patients who achieved a complete remission or complete remission with an incomplete count recovery achieved progression-free survival, and 1 had relapsed.

At 6 months, the progression-free survival rate among 13 patients was 91.7%.

Six patients were successfully bridged to receive allo-HCT after 22-CAR-T therapy.

Importantly, most patients had no or low-grade cytokine release syndrome, which is a common and potentially severe side effect of CAR-T therapy. Rates of cytokine release syndrome did not differ based on whether patients did or did not undergo allo-HCT. Two patients had low-grade 1 neurotoxicity.

No patients have died in the study, and no severe toxicities have been observed.

The improvements are encouraging considering the patients' poor prognoses, Pan said.

"These are all patients who would die without CD22-CAR-T," she told Medscape Medical News.

"We think CAR T-cell therapy induces remission, and bridging to allo-HCT is the key point for this excellent long-term outcome."

Pan noted that CD19 CAR T-cell therapy is nevertheless still the primary option for r/r B-ALL.

"The complete remission rate of CD19-CAR T-cell therapy in our hospital is up to 95%, so this is still the first choice," Pan said.

Findings Are "Notable"

In commenting on the new study, Anton Hagenbeek, MD, PhD, professor of hematology in the Academic Medical Center at the University of Amsterdam, the Netherlands, agreed that the findings are notable.

"I was surprised that patients were so sensitive to CD22 after relapsing on CD19, and I think it is very promising data," he told Medscape Medical News.

Hagenbeek added that "the follow-up is short —  about 200 days; however, no one is relapsing. These are high-risk patients, and if they relapse they relapse early, and  this is promising."

He underscored that the complete remission rate is highly encouraging.

"The 80% complete remission rate is amazing — these are patients who are refractory to chemotherapy, with many who are negative of MRD, so this is really breakthrough medicine," he commented.

Pan and Hagenbeek have disclosed no relevant financial relationships.

European Hematology Association (EHA) 2018 Congress. Abstract S832. Presented June 16, 2018.

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