Clinicopathologic features of relapsed CD19(−) B‐ALL in CD19‐targeted immunotherapy: Biological insights into relapse and LILRB1 as a novel B‐cell marker for CD19(−) B lymphoblasts

Abstract Introduction The mechanism of relapsed CD19(−) B‐ALL after anti‐CD19 immunotherapy (Kymriah [CART‐19] and blinatumomab) is under active investigation. Our study aims to assess LILRB1 as a novel B‐cell marker for detecting CD19(−) B‐lymphoblasts and to analyze the clinicopathologic/genetic features of such disease to provide biological insight into relapse. Methods Six patients (3 males/3 females, median age of 14 years) with relapsed CD19(−) B‐ALL were analyzed for cytogenetic/genetic profile and immunophenotype. Results CD19(−) B‐ALL emerged after an interval of 5.8 months following anti‐CD19 therapy. Five of six patients had B‐cell aplasia, indicative of a persistent effect of CART or blinatumomab at relapse. Importantly, LILRB1 was variably expressed on CD19(−) and CD19(+) B lymphoblasts, strong on CD34(+) lymphoblasts and dim/partial on CD34(−) lymphoblasts. Three of six patients with paired B‐ALL samples (pre‐ and post‐anti‐CD19 therapy) carried complex and different cytogenetic abnormalities, either as completely different or sharing a subset of cytogenetic abnormalities. Conclusion LILRB1 can be used as a novel B‐cell marker to identify CD19(−) B lymphoblasts. The emergence of CD19(−) B‐ALL appears to be associated with complex cytogenetic evolutions. The mechanism of CD19(−) B‐ALL relapse under anti‐CD19 immune pressure remains to be explored by comprehensive molecular studies.