Pediatric and Young Adult Patients Benefit from Tisagenlecleucel Immunotherapy for Relapsed/Refractory B-ALL

Introduction

A recent industry-funded study has reported that the profile of pediatric and young adult patients who undergo tisagenlecleucel (Kymriah) has evolved significantly in the last four years. Patients with less severe relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) are increasingly receiving tisagenlecleucel, with more patients bypassing hematopoietic stem cell transplantation (HSCT). The study also found that the survival rate of patients who didn’t undergo post-infusion HSCT has increased from 18 to 27 months in two years. The aim of this article is to discuss these study findings and their implications for the treatment of pediatric and young adult patients with relapsed/refractory B-ALL, including disease burden, remission rates, and adverse effects.

Evolution of Pediatric and Young Adult Patients Profile

The study included 974 patients up to age 25 who received tisagenlecleucel in the US, Canada, Korea, and Taiwan. The study findings indicate that the percentage of patients who have a disease burden of ≥50% fell from 18% to 4%. Patients with less severe disease are increasingly receiving tisagenlecleucel, and the therapy is becoming more than “a last resort” for those with second or greater relapse or who are refractory. By offering CAR T-cell therapy to earlier-stage patients, practitioners could potentially save them from having to go on to a transplant. The findings may indicate providers are becoming more comfortable with getting their patients in the best shape before getting CAR T-cell therapy. Outcomes are improving as providers expand the use of CAR T-cell therapy to patients who are less heavily pretreated and have lower disease burden.

Remission Rates

According to Dr. Nirali N. Shah, head of the Pediatric Oncology Branch’s Hematologic Malignancies Section at the National Cancer Institute, remission rates have been around 60%-70%, although the rate is “likely higher” now due to gains in experience and improvement in disease burden before therapy. The introduction of tisagenlecleucel has changed the treatment landscape for refractory B-ALL, where the standard of care previously would be to proceed to transplant. The study suggests that “a substantial number of patients are surviving. It’s remarkable actually. Prior to tisagenlecleucel, patients had dismal outcomes from standard chemotherapy.”

Adverse Effects

The study indicates that disease burden has a pretty direct relationship with side effects and toxicities. If patients have more disease, they experience more severe side effects. Reducing disease burden may reduce side effects. Management of the toxicities associated with tisagenlecleucel therapy has improved. Eliminating some of the more toxic chemotherapy through earlier use of CAR T-cells in chemotherapy-refractory patients may well help reduce the therapy burden and improve long-term survival outcomes.

Cost

According to drugs.com, the therapy costs more than $612,000 per infusion. Dr. Shah reports that insurers are covering the treatment. There are also efforts to expand the indication so CAR T-cell therapy can be used earlier in patients who are chemotherapy-refractory. Novartis has funded the study, and Dr. Shah discloses ties with Lentigen, VOR, and CARGO, ImmunoACT, and Sobi. Dr. Rouce reports relationships with Pfizer and Novartis.

Conclusion

Overall, the study findings are promising for pediatric and young adult patients with relapsed/refractory B-ALL who undergo tisagenlecleucel therapy. More patients with less severe disease are receiving this therapy, bypassing the need for HSCT. The survival rate of patients who did not undergo post-infusion HSCT has increased. Remission rates have improved, and adverse effects have been better managed. Efforts are being made to expand the indication of tisagenlecleucel therapy to include patients who are chemotherapy-refractory. While the treatment costs are high, insurers are covering the treatment costs and may improve access for patients. Further research may reveal how to improve outcomes even more and potentially cure more patients previously thought to be incurable.

Originally Post From https://www.mdedge.com/hematology-oncology/article/269486/all/car-t-b-all-game-changer-young-patients

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