1.
Longitudinal Patient Reported Outcomes with CAR-T Cell Therapy vs Autologous and Allogeneic Stem Cell Transplant
Sidana, S., Dueck, A. C., Thanarajasingam, G., Griffin, J. M., Thompson, C., Durani, U., Burtis, M., Warsame, R., Paludo, J., Gertz, M. A., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND There is limited data on patient experience after chimeric antigen receptor (CAR) T cell therapy, especially in comparison to autologous and allogeneic transplant, which are more established forms of cellular therapy. OBJECTIVE We prospectively evaluated longitudinal patient-reported quality of life (QoL), symptom burden and cognition after CAR-T cell therapy and compared it with prospective cohorts of patients undergoing autologous stem cell transplant (autoSCT) and allogeneic SCT (alloSCT). STUDY DESIGN This was a single center study. The primary endpoint was change in QoL. Secondary endpoints were patient-reported adverse events (PRO-AEs) measured by PRO-CTCAE and cognitive function (NeuroQOLv2 questionnaire). Time profile of PRO-AEs was evaluated using longitudinal analysis Toxicity over Time (ToxT). Patients completed questionnaires at baseline, week 2 and monthly for 6 months. RESULTS 104 patients were evaluable (CAR-T: 34, autoSCT: 33, alloSCT: 37). Baseline QoL was similar across groups. We observed a short-term decline in QoL in all groups that gradually returned to baseline. The nadir in QoL was at week 2 and coincided with peak in symptom burden. The decline in overall QoL, physical and functional well-being was significantly less with CAR-T vs. SCT groups and returned to baseline faster. Patients in the alloSCT group experienced the greatest symptom burden, greater decrease in performance status, largest short-term decline in QoL and slowest recovery. CONCLUSION This study provides comprehensive data comparing QoL, PRO-AEs and cognition in CAR-T cell therapy vs. autoSCT and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional domains was better in the CAR-T group vs. SCT groups, although all groups experienced an initial decline coinciding with peak symptoms. These data can serve as a guide for patient education, symptom management, and future studies in CAR-T cell therapy.
2.
Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplant
Prockop, S., Doubrovina, E., Suser, S., Heller, G., Barker, J., Dahi, P., Perales, M. A., Papadopoulos, E., Sauter, C., Castro-Malaspina, H., et al
The Journal of clinical investigation. 2019
Abstract
BACKGROUND Adoptive transfer of donor-derived EBV-specific T-cells (EBV-CTLs) can eradicate EBV associated lymphomas post hematopoietic cell (HCT) or solid organ (SOT) transplants but is not available for most patients. METHODS We developed a 3rd-party, allogeneic, off-the-shelf bank of 330 GMP grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (N=33) or SOT (N=13) with established EBV associated lymphomas, who failed rituximab therapy, with 3rd-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation. RESULTS The EBV-CTLs did not induce significant toxicities or graft injury. One patient developed grade I skin GVHD requiring topical therapy. Complete and sustained partial remissions were achieved in 68% of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, overall survival was 88.9% and 81.8% respectively at 1 year. Although only 1/11 patients (9.1%) with progression of disease (POD) after cycle 1 who received additional EBV-CTLs from the same donor survived, 3 of 5 with POD subsequently treated with EBV-CTLs from a different donor achieved CR or durable PR (60%) and survive > 1 year. Maximal responses were achieved after a median of 2 cycles. CONCLUSIONS Third party EBV-CTLs of defined HLA restriction provide safe, immediately accessible treatment for EBV PTLD. Secondary treatment with EBV-CTLs restricted by a different HLA allele (switch therapy) can also induce remissions if initial EBV-CTLs are ineffective. These results suggest a promising potential therapy for patients with rituximab refractory EBV-associated lymphoma post transplant.Phase II protocols (NCT01498484 and NCT00002663) were approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center, Food and Drug Administration and National Marrow Donor Program.This work was supported through NIH grants CA23766, NIH R21CA162002, Aubrey Fund, The Claire Tow Foundation, Major Family Foundation, Max Cure Foundation, Richard "Rick" J. EIsemann Pediatric Research Fund, Banbury Foundation, Edith Robertson Foundation, Larry Smead Foundation. In June 2015 Atara Biotherapeutics licensed the EBV-CTL bank and is developing this as ATA-129.