NEJM Long-Term Data Show 10-Year Relapse-Free Survival After Single Tisagenlecleucel Infusion in B-Cell Lymphoma

{"The analysis followed 38 patients with relapsed or refractory disease who had received a median of four prior therapies. Median follow-up reached 10 years. No relapses occurred after 5.4 years. CAR T-cell persistence in peripheral blood during the first two years correlated more strongly with durable response than peak expansion. More than half of long-term responders recovered normal B-cell counts without lymphoma recurrence.","Two patients had persistent grade 2-3 neutropenia; nine developed second primary cancers, a rate consistent with prior chemotherapy and transplant exposure in lymphoma cohorts. No CAR T-related secondary lymphomas were observed. These safety signals occurred in a heavily pretreated population, limiting direct attribution to the CAR T product itself.","The durability signal supports testing CAR T earlier in the disease course, before cumulative genotoxic damage. Resource allocation questions arise: if a meaningful fraction of patients are functionally cured, the high upfront cost may be offset by avoided subsequent lines of therapy and transplant-related morbidity.","Next steps include randomized trials moving tisagenlecleucel into second-line settings and correlative studies of T-cell fitness and tumor microenvironment to raise response rates above the current one-third to one-half range."}