Life Science Review Europe.

Next-generation sequencing significantly predicts likelihood for recurrence in patients treated with tisagenlecleucel. 41 of 42 patients relapsed or advanced to HCT or other treatments after treatment with Kymriah, according to scientists at Utah's Huntsman Cancer Institute.

FREMONT, CA: A recent research found that detecting minimal residual illness using next-generation sequencing was significantly predictive of recurrence in adolescents and young adults with acute lymphoblastic leukemia treated with tisagenlecleucel (Kymriah). Every timepoint from 3 to 12 months following therapy had the detectable disease, with 41 of 42 patients relapsing or advancing to HCT or other treatments, according to Michael Pulsipher, MD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

A threshold of >0 cells observed is the best biomarker reported so far to predict the likelihood for recurrence following CAR T-cell treatment with tisagenlecleucel, scientists noted in Blood Cancer Discovery. First-year B-cell aplasia also defines patients with potential long-term response. HCT or other cell or immune therapy should be tried for those who lose B-cell aplasia or have NGS-MRD measurements >0 on marrow examination .

Multiparametric flow cytometry (MFC) has shown that second-generation CAR T-cell treatments result in MRD-negative remissions in 80-97% of patients. There are no reliable signs to predict recurrence in these individuals, which is one of the obstacles in treating them.

Sara Ghorashian, BM BCh, PhD, and Jack Bartram, BM BCh, of Great Ormond Street Hospital for Children in London,  said that  these results clearly show that NGS-MRD may predict relapse after tisagenlecleucel infusion, accompanying the study. Pulsipher and colleagues compared MFC-MRD with NGS-MRD in 1,771 MFC samples from 143 paediatric and young adult patients involved in the ENSIGN and ELIANA studies.

NGS-MRD was able to detect individuals at risk of recurrence far in advance of relapse in all patients, the scientists observed. The median time to relapse among patients with MRD was 52 days from the first MFC, 70 days from NGS-MRD over the threshold of 106, and 168 days from NGS-MRD below the 106 cutoffs. A combination of B-cell aplasia and bone marrow NGS-MRD measurements was shown to be relevant, since patients who lose B-cell aplasia early perform poorly.