Weathering the storm when the end of the road is near: A qualitative analysis of supportive care needs during CAR T-cell therapy in pediatrics.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy provides promising outcomes in relapsed/refractory B acute lymphoblastic leukemia (ALL), yet still carries high toxicity rates and relatively poor long-term survival. Efficacy has yet to be demonstrated in other diagnoses while toxicity and risk profiles remain formidable. To date, treatment-related symptom burden is gleaned from clinical trial toxicity reports; the patient perspective remains understudied. METHODS: English- or Spanish-speaking patients (ages 8-25 years) undergoing CAR T-cell therapy for any malignancy and their primary caregivers were recruited from Seattle Children's Hospital (SCH), St. Jude Children's Research Hospital (SJCRH), and the Pediatric Oncology Branch of the National Cancer Institute (NCI). Both patient and caregiver completed semi-structured dyadic interviews 3 months post treatment. We used directed content analysis for codebook development and thematic network analysis for inductive qualitative analysis. RESULTS: Twenty families completed interviews (13 patients, 15 parents). Patients were a median age 16.5 years, predominantly female (65%), White (75%), and diagnosed with ALL (75%). Global themes included "A clear decision," "Coping with symptoms," and "Unforeseen psychosocial challenges." When families were asked to describe the "most challenging part of treatment," most described "the unknown." Most reported "the symptoms really weren't that bad," even among patients hospitalized for severe toxicity events. Fatigue, pain, and nausea were the most prevalent symptoms. Importantly, only one family would have chosen a different therapy, if given another opportunity. CONCLUSIONS: Although physical symptoms were largely tolerable, recognizing supportive care opportunities remains imperative, particularly psychosocial concerns.

A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials.

The tremendous success of chimeric antigen receptor (CAR) T cells in children and young adults (CAYAs) with relapsed/refractory B-cell acute lymphoblastic leukemia is tempered by toxicities such as cytokine release syndrome (CRS). Despite expansive information about CRS, profiling of specific end-organ toxicities secondary to CAR T-cell therapy in CAYAs is limited. This retrospective, single-center study sought to characterize end-organ specific adverse events (AEs) experienced by CAYAs during the first 30 days after CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events were retrospectively analyzed for 134 patients enrolled in 1 of 3 phase 1 CAR T-cell trials (NCT01593696, NCT02315612, and NCT03448393), targeting CD19 and/or CD22. A total of 133 patients (99.3%) experienced at least 1 grade ≥3 (≥Gr3) AE across 17 organ systems, of which 75 (4.4%) were considered dose- or treatment-limiting toxicities. Excluding cytopenias, 109 patients (81.3%) experienced a median of 3 ≥Gr3 noncytopenia (NC) AEs. The incidence of ≥Gr3 NC AEs was associated with the development and severity of CRS as well as preinfusion disease burden (≥ 25% marrow blasts). Although those with complete remission trended toward experiencing more ≥Gr3 NC AEs than nonresponders (median, 4 vs 3), nonresponders experiencing CRS (n = 17; 37.8%) had the highest degree of NC AEs across all patients (median, 7 vs 4 in responders experiencing CRS). Greater understanding of these toxicities and the ability to predict which patients may experience more toxicities is critical as the array of CAR T-cell therapies expand. This retrospective study was registered at www.clinicaltrials.gov as NCT03827343.

Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion.

Chimeric antigen receptor (CAR) T cells have emerged as a potent therapeutic approach for patients with certain haematological cancers, with multiple CAR T cell products currently approved by the FDA for those with relapsed and/or refractory B cell malignancies. However, in order to derive the desired level of effectiveness, patients need to successfully receive the CAR T cell infusion in a timely fashion. This process entails apheresis of the patient's T cells, followed by CAR T cell manufacture. While awaiting infusion at an authorized treatment centre, patients may receive interim disease-directed therapy. Most patients will also receive a course of pre-CAR T cell lymphodepletion, which has emerged as an important factor in enabling durable responses. The time between apheresis and CAR T cell infusion is often not a simple journey, with each milestone being a critical step that can have important downstream consequences for the ability to receive the infusion and the strength of clinical responses. In this Review, we provide a summary of the many considerations for preparing patients with B cell non-Hodgkin lymphoma or acute lymphoblastic leukaemia for CAR T cell therapy, and outline current limitations and areas for future research.