ABSTRACT
Background: The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized treatment outcomes in patients with lymphoid malignancies. However, several studies have reported a relatively high rate of infection in adult patients following CD19-targeting CAR T-cell therapy, particularly in the first 28 days. Notably, acute human herpesvirus 6 B (HHV6B) reactivation occurs in up to two-thirds of allogeneic hematopoietic stem cell transplantation patients. Case presentations: Herein, we describe a report of HHV6B encephalitis/myelitis in three patients with relapsed/refractory diffuse large B-cell lymphoma post CAR T-cell therapy. All three patients received multiple lines of prior treatment (range: 2-9 lines). All patients presented with fever that persisted for at least 2 weeks after CAR-T cell infusion (CTI). Both the onset time and duration were similar to those of the cytokine release syndrome (CRS); nevertheless, the CRS grades of the patients were low (grade 1 or 2). Delirium and memory loss after CTI were the earliest notable mental presentations. Neurological manifestations progressed rapidly, with patients experiencing varying degrees of impaired consciousness, seizures, and coma. Back pain, lumbago, lower limb weakness and uroschesis were also observed in Patient 3, indicating myelitis. High HHV6B loads were detected in all Cerebral spinal fluid (CSF) samples using metagenomic next-generation sequencing (mNGS). Only one patient required high-activity antivirals and IgG intravenous pulse treatment finally recovered, whereas the other two patients died from HHV6B encephalitis. Conclusion: Considering its fatal potential, HHV6B encephalitis/myelitis should be urgently diagnosed post CAR-T cell-based therapy. Furthermore, hematologists should differentially diagnose these conditions from CRS or other immunotherapy-related neurotoxicities as early as possible. The results of this study demonstrate the potential of mNGS in the early diagnosis of HHV6B infection, particularly when the organism is difficult to culture.
ABSTRACT
Genetically modified T-cell immunotherapies are revolutionizing the therapeutic options for hematological malignancies, especially those of B-cell origin. Impressive efficacies of CD19-directed chimeric antigen receptor (CAR)-T therapy have been reported in refractory/relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL) patients who were resistant to current standard therapies, with a complete remission (CR) rate of approximately 50%. At the same time, problems of resistance and relapse following CAR-T therapy have drawn growing attention. Recently, great efforts have been made to determine various factors that are connected to the responses and outcomes following CAR-T therapy, which may not only allow us to recognize those with a higher likelihood of responding and who could benefit most from the therapy but also identify those with a high risk of resistance and relapse and to whom further appropriate treatment should be administered following CAR-T therapy. Thus, we concentrate on the biomarkers that can predict responses and outcomes after CD19-directed CAR-T immunotherapy. Furthermore, the mechanisms that may lead to treatment failure are also discussed in this review.
