Children and young adults with relapsed or refractory ALL who receive chimeric antigen receptor (CAR) T-cell therapy targeting CD22, a protein found on the surface of leukaemic cancer cells, appear to mount a clinical response and in some cases may achieve remission.

Researchers from the Pediatric Oncology Branch of the National Cancer Institute of the National Institutes of Health genetically altered patients’ own T cells to track down and kill cancer cells expressing CD22.

The study presented at ASH 2016 — the first to evaluate this new target for immunotherapy in humans — also gives a first glimpse into how patients who already received CAR-T therapy directed at a different antigen, CD19, might fare when given a second immunotherapy.

Early findings from this Phase I clinical trial demonstrated that the first three patients treated at the second dose level attained a complete remission without any evidence of residual disease.

Based on these initial results, the researchers treated more patients (16 in total) and found that eight of the 10 patients attained complete remission when treated at the top dose levels.

“We’ve been able to show that you can give a second CAR therapy that is directed against a different antigen and have it be safe and effective,” said study author Terry J. Fry, MD, of the Center for Cancer Research, National Cancer Institute in Bethesda, Md.

Dr. Fry said this adds to the notion that a single antigen-directed CAR immunotherapy probably won’t be sufficient for long-term durable remissions in many patients and points to the potential for targeting multiple cancer-related proteins (also called bispecific targeting).

The trial included 16 patients with relapsed or treatment-resistant ALL who were either CAR naïve or previously treated with anti-CD19 CAR T cells and/or blinatumomab therapy and had relapsed with CD19 negative disease.

The patients, ranging in age from 7– 22 years old, all had CD22 ALL and had previously undergone at least one allogeneic stem cell transplant.

The majority of treated patients had relapsed after an earlier anti-CD19 CAR T cell before entering the trial.

Researchers then collected T cells from eligible patients and modified them to recognise and bind to CD22.

Patients then received an infusion of their own enhanced cells and were evaluated for response and adverse effects after an average of 28 days.

While the trial is continuing to accrue patients, these early results raise new questions about how anti-CD22 CAR therapy might best be used; for example, if it is better to wait for relapse after initial CAR therapy or preempt it by co-treating it.

Dr. Fry and team plan to investigate the combined use of anti-CD19 and CD22 CAR targeting approaches with the hypothesis that this will increase the likelihood of sustained remission.

Terry J. Fry, MD, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., will present this study during the ASH press conference. Nirali N. Shah, MD, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., will present this study during an oral presentation on Monday, December 5 at 7:15 a.m. in Room 6CF of the San Diego Convention Center.

Source: ASH 2016