Rare Sequences Make Sense of CAR T-cell Therapy Outcomes

Abstract

In this issue, Pulsipher and colleagues used next-generation sequencing to detect leukemia-specific sequences following tisagenlecleucel therapy of acute lymphoblastic leukemia. A challenge for the field currently is to identify which patients will have therapy failure and to do so early enough to allow planning for further treatment, for example, stem cell transplantation. Detection of disease below the standard detection level for this technique (less than one per million cells) at day 28 was associated with poorer outcomes and potentially therefore could be used to identify those that might benefit from adjunctive therapies.See related article by Pulsipher et al., p. 66.

Figure 1.

Comparison of relative sensitivities of MRD assessment methods and corresponding levels of disease. The left column refers to the estimated total leukemic cells (leukemic burden) in the body at a given MRD level. The median interval to relapse from detection of a positive MRD result, the “detection window” adapted from Pulsipher and colleagues (9), is shown in the far-right column for MFC-MRD, for NGS-MRD at a level of sensitivity cutoff at 10⁻⁶, and for NGS-MRD at any detectable level. QA, quality assurance.