TY - JOUR
T1 - Patient-Reported Symptom and Functioning Status during the First 12 Months after Chimeric Antigen Receptor T Cell Therapy for Hematologic Malignancies
AU - Wang, Xin Shelley
AU - Srour, Samer A.
AU - Whisenant, Meagan
AU - Subbiah, Ishwaria M.
AU - Chen, Tsun Hsuan
AU - Ponce, Darcy
AU - Gonzalez, Araceli Garcia
AU - Kamal, Mona
AU - Mendoza, Tito
AU - Cleland, Charles S.
AU - Kebriaei, Partow
AU - Neelapu, Sattva S.
AU - Rezvani, Katayoun
AU - Ahmed, Sairah
AU - Shpall, Elizabeth
N1 - Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy
PY - 2021/11
Y1 - 2021/11
N2 - Chimeric antigen receptor (CAR) T cell therapy is being increasingly used to treat patients with advanced hematologic malignancies; however, the symptoms related to standard of care CAR T cell therapy during the first year after treatment have not been assessed using patient-reported outcome (PRO) measurements. This study aimed to quantify patients’ perspectives of symptom burden and functional status using PROs during the first year after CAR T cell therapy for hematologic malignancies, especially in patients who experienced grade 2-4 toxicities. Sixty patients were enrolled in this observational cross-sectional study at any time during their first 12 months post-treatment. All 60 had received CAR T cell therapy as standard of care at MD Anderson Cancer Center in 2019. PROs were measured using the MD Anderson Symptom Inventory (MDASI), the PROs Measurement Information System 29 (PROMIS-29), the global health tool EQ5D-5L, and the single-item health-related quality of life scale (HRQoL). Twenty-two additional symptoms related to CAR T cell therapy, as identified by an expert panel, were also evaluated. CAR T cell therapy-related toxicities were rated according to the ASTCT consensus grading criteria. The majority of patients (52 of 60; 87%) received axicabtagene ciloleucel (Yescarta). One-third of the patients developed grade 2-4 cytokine release syndrome or neurotoxicity. The first 90 days after infusion represented the most symptomatic period, in which >10% of patients rated 18 symptoms as severe (ie, MDASI symptom score of 7 to 10 on scale of 0 to 10), strongly indicating the need for effective symptom management. Physical functioning, measured by interference on the “general activity” item on the MDASI and this domain on the PROMIS-29, were significantly worse in patients who underwent therapy during the first 30 days compared with those who underwent therapy over 90 days (all P <.05 with the Hochberg step-up procedure), whereas the EQ5D-5L and single-item HRQoL did not detect such differences. Compared with patients who had mild cytokine release syndrome or neurotoxicity (grade 0-1), patients who developed grade 2-4 toxicities persistently reported multiple severe symptoms after 30 days following therapy (all P <.05). Furthermore, although using a different recall period, patient-reported scores on several PROMIS-29 domains were significantly correlated with the scores of corresponding MDASI symptom items. This real-world quantitative PRO symptoms study provides evidence of unique profiles of the physical, psychological, and cognitive symptom burden in patients undergoing CAR T cell therapy that varies within the first year after infusion and demonstrates differences among PRO measurement scales. These results support the need for validation of fit-for-purpose PRO measurements for routinely monitoring symptom and toxicity burdens in CAR T cell therapy care settings.
AB - Chimeric antigen receptor (CAR) T cell therapy is being increasingly used to treat patients with advanced hematologic malignancies; however, the symptoms related to standard of care CAR T cell therapy during the first year after treatment have not been assessed using patient-reported outcome (PRO) measurements. This study aimed to quantify patients’ perspectives of symptom burden and functional status using PROs during the first year after CAR T cell therapy for hematologic malignancies, especially in patients who experienced grade 2-4 toxicities. Sixty patients were enrolled in this observational cross-sectional study at any time during their first 12 months post-treatment. All 60 had received CAR T cell therapy as standard of care at MD Anderson Cancer Center in 2019. PROs were measured using the MD Anderson Symptom Inventory (MDASI), the PROs Measurement Information System 29 (PROMIS-29), the global health tool EQ5D-5L, and the single-item health-related quality of life scale (HRQoL). Twenty-two additional symptoms related to CAR T cell therapy, as identified by an expert panel, were also evaluated. CAR T cell therapy-related toxicities were rated according to the ASTCT consensus grading criteria. The majority of patients (52 of 60; 87%) received axicabtagene ciloleucel (Yescarta). One-third of the patients developed grade 2-4 cytokine release syndrome or neurotoxicity. The first 90 days after infusion represented the most symptomatic period, in which >10% of patients rated 18 symptoms as severe (ie, MDASI symptom score of 7 to 10 on scale of 0 to 10), strongly indicating the need for effective symptom management. Physical functioning, measured by interference on the “general activity” item on the MDASI and this domain on the PROMIS-29, were significantly worse in patients who underwent therapy during the first 30 days compared with those who underwent therapy over 90 days (all P <.05 with the Hochberg step-up procedure), whereas the EQ5D-5L and single-item HRQoL did not detect such differences. Compared with patients who had mild cytokine release syndrome or neurotoxicity (grade 0-1), patients who developed grade 2-4 toxicities persistently reported multiple severe symptoms after 30 days following therapy (all P <.05). Furthermore, although using a different recall period, patient-reported scores on several PROMIS-29 domains were significantly correlated with the scores of corresponding MDASI symptom items. This real-world quantitative PRO symptoms study provides evidence of unique profiles of the physical, psychological, and cognitive symptom burden in patients undergoing CAR T cell therapy that varies within the first year after infusion and demonstrates differences among PRO measurement scales. These results support the need for validation of fit-for-purpose PRO measurements for routinely monitoring symptom and toxicity burdens in CAR T cell therapy care settings.
KW - CAR T cell therapy
KW - Functioning measure
KW - Hematologic malignancies
KW - Patient-reported outcomes
KW - Symptoms
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U2 - 10.1016/j.jtct.2021.07.007
DO - 10.1016/j.jtct.2021.07.007
M3 - Article
C2 - 34265479
AN - SCOPUS:85118509599
SN - 2666-6367
VL - 27
SP - 930.e1-930.e10
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 11
ER -