Fachthema

Acute lymphocytic leukemia

A first stem cell transplant after CAR-T-cell therapy reduces relapses

Jatros Digital, 01.12.2018
Onkologie | Hämatologie

In a new study, patients with acute lymphocytic leukemia (ALL) who received a first stem cell transplant after CD19 CAR-T-cell therapy were less likely to experience a relapse when compared to similar patients who didn’t undergo transplantation.

In this phase I/II trial 64 ALL-patients were analyzed who had received an infusion of their own T-cells that had been reprogrammed to recognize and target CD19. Patients had previously relapsed or had not responded to other treatment. Follow-up monitoring occurred for at least one year.
14 patients relapsed, died, or did not respond to the CAR-T-cell therapy. Of the 50 patients who achieved a sustained remission after CAR-T-cell therapy, 34 had a history of previous stem cell transplant.
There were several cohorts observed:

  • Of 24 patients who had a previous stem cell transplant but did not undergo a second one following CAR-T-cell therapy, 7 remain in remission.
  • Among the 10 patients who had their second stem cell transplant following CAR-T-cell therapy, 5 remain alive and in remission after at least 24 months of follow-up.
  • Among the 16 patients who had not had a previous stem cell transplant, 13 had one after receiving CAR-T-cell therapy. One of these patients relapsed following the stem cell transplant.
  • Of the 3 patients who did not have a stem cell transplant after CAR-T-cell therapy, two relapsed and the third remains in remission after 28 months of follow-up.

One of the expected effects of CAR-T-cell therapy is B-cell aplasia. Continued B-cell aplasia is regarded as an indicator that the CAR-T-cells are still actively preventing the patient’s cancer from coming back. By contrast, short B-cell aplasia indicates that the CAR-T-cells may no longer be working.
In the current analysis of patients who had been followed for at least a year, those with short B-cell aplasia who had a stem cell transplant after CAR-T-cell therapy were less likely to relapse, regardless of whether the transplant was their first or their second. In this group of 8 patients, 1 died of transplant-related complications and 2 relapsed. By contrast, all 6 patients with short B-cell aplasia who did not undergo stem cell transplant after CAR-T-cell therapy relapsed.
Among patients who had a stem cell transplant after CAR-T-cell therapy, all relapses thus far have occurred within two years, said Dr. Summers. However, among patients who did not have a stem cell transplant following CAR-T-cell therapy, relapses continue to occur two or more years after treatment.
„For pediatric patients who achieve remission after CAR-T-cell therapy, undergoing a first stem cell transplant following CD19 CAR-T-cell therapy appears to be beneficial,‟ said Dr. Summers. „For patients who achieve remission, but have a higher risk of relapse because of short B-cell aplasia, a stem cell transplant after CAR-T-cell therapy appears to be beneficial whether or not they have had one previously.‟
For patients with a previous stem cell transplant, the benefit of a second one after CAR-T-cell therapy is unclear; it may be that among this group of patients, only those with short B-cell aplasia benefit from a second transplant, according to the authors.
Longer follow-up is needed to understand the reasons for long-term relapse after CD19 CAR-T-cell therapy and whether patients with a prior stem cell transplant can benefit from receiving a second one following CAR-T-cell therapy. Phase II of the trial, now underway, is testing the anti-CD19 CAR-T-cell therapy in a larger group of patients with acute leukemia or lymphoma that has relapsed or been unresponsive to other therapy.


Reference:
Summers C et al.: long term follow-up after SCRI-CAR19v1 reveals late recurrences as well as a survival advantage to consolidation with HCT after CAR-T cell induced remission. ASH Annual Meeting 2018, abstract #967