Contributions
Abstract: PB1735
Type: Publication Only
Session title: Quality of life, palliative care, ethics and health economics
Background
Refractory/relapsed B-cell precursor acute lymphoblastic leukemia (r/r ALL) is an acute disease with poor prognosis with standard of care. The value of chimeric antigen receptor (CAR) T-cell therapies on not only overall survival but also health-related quality of life in r/r ALL warrants further study. The ZUMA-3 open-label, phase 1/2 multicenter trial (NCT02614066) was designed to evaluate the safety and efficacy of KTE-X19 in adult subjects with r/r ALL.
Aims
This analysis aimed to evaluate health-related quality of life as measured by the EQ-5D within the ZUMA-3 trial and how scores changed after treatment with KTE-X19 as compared to before treatment.
Methods
The EQ-5D 5 level version (EQ-5D-5L) was used to assess quality of life among patients in the Phase 2 portion of the ZUMA-3 trial at Screening, Day 28, Month 3, and every 3 months during long-term follow-up (up to 12 months). The EQ-5D visual analog scale (VAS) and Index scores (calculated using the US value set, with sensitivity analyses using crosswalk of UK, German, and French value sets) were described at screening, Day 28 and Months 3, 6, 9, and 12 with changes in scores from screening compared to thresholds for meaningful change (7 for VAS, 0.05 for EQ-5D indices). To handle missing survey response data, mixed-effects models with repeated measures (MMRMs) using a categorical variable for visit were applied under the missing-at-random assumption to estimate changes in scores in the full study population.
Results
Among 55 treated subjects in the Phase 2 modified intent to treat (mITT) study population, 51 patients completed the EQ-5D-5L survey at screening, 42 (41 for Index) at Day 28, 26 (25 for Index) at Month 3, 25 at Month 6, 10 at Month 9 and 14 at Month 12. Mean (SD) VAS scores at Screening, Day 28, Month 3, Month 6, Month 9, and Month 12 were 68.2 (21.8), 74.7 (17.9), 79.7 (12.2), 81.0 (17.6), 81.7 (23.1), and 86.9 (10.0) respectively. Most patients (min 70.0%, max 92.9%) had stable or improved VAS scores after treatment with KTE-X19.
Mean (SD) EQ-5D Index scores (US value set) were 0.82 (0.19) at screening with the highest score at Month 12 (0.91 [0.13]). Most patients had stable or improved EQ-5D Index scores after treatment with KTE-X19 (min: 57.5% [Day 28] max: 80.0% [Month 9]). Results were similar using UK, German, and French EQ-5D-5L index value sets. Based on MMRMs, estimated mean change in VAS exceeded clinically meaningful thresholds at Month 3 (mean [95% CI]: 9.6 [2.6, 16.5]), Month 6 (9.4 [2.5, 16.3]), and Month 12 (14.8 [7.0, 22.6]). Estimated mean change in EQ-5D-5L indices exceeded clinically meaningful thresholds at Month 12 (0.078 [-0.009, 0.164]) but confidence intervals overlapped 0. Similar to other patient outcome survey studies, results should be interpreted with caution due to missing follow-up data for some patients and small sample size.
Conclusion
Results showed that among R/R ALL patients participating in ZUMA-3, the majority of patients experienced improved or stable health-related quality of life as assessed by the EQ-5D scores, and this was more pronounced with the VAS score.
Keyword(s): B cell acute lymphoblastic leukemia, CAR-T, Quality of life, Relapsed acute lymphoblastic leukemia
Abstract: PB1735
Type: Publication Only
Session title: Quality of life, palliative care, ethics and health economics
Background
Refractory/relapsed B-cell precursor acute lymphoblastic leukemia (r/r ALL) is an acute disease with poor prognosis with standard of care. The value of chimeric antigen receptor (CAR) T-cell therapies on not only overall survival but also health-related quality of life in r/r ALL warrants further study. The ZUMA-3 open-label, phase 1/2 multicenter trial (NCT02614066) was designed to evaluate the safety and efficacy of KTE-X19 in adult subjects with r/r ALL.
Aims
This analysis aimed to evaluate health-related quality of life as measured by the EQ-5D within the ZUMA-3 trial and how scores changed after treatment with KTE-X19 as compared to before treatment.
Methods
The EQ-5D 5 level version (EQ-5D-5L) was used to assess quality of life among patients in the Phase 2 portion of the ZUMA-3 trial at Screening, Day 28, Month 3, and every 3 months during long-term follow-up (up to 12 months). The EQ-5D visual analog scale (VAS) and Index scores (calculated using the US value set, with sensitivity analyses using crosswalk of UK, German, and French value sets) were described at screening, Day 28 and Months 3, 6, 9, and 12 with changes in scores from screening compared to thresholds for meaningful change (7 for VAS, 0.05 for EQ-5D indices). To handle missing survey response data, mixed-effects models with repeated measures (MMRMs) using a categorical variable for visit were applied under the missing-at-random assumption to estimate changes in scores in the full study population.
Results
Among 55 treated subjects in the Phase 2 modified intent to treat (mITT) study population, 51 patients completed the EQ-5D-5L survey at screening, 42 (41 for Index) at Day 28, 26 (25 for Index) at Month 3, 25 at Month 6, 10 at Month 9 and 14 at Month 12. Mean (SD) VAS scores at Screening, Day 28, Month 3, Month 6, Month 9, and Month 12 were 68.2 (21.8), 74.7 (17.9), 79.7 (12.2), 81.0 (17.6), 81.7 (23.1), and 86.9 (10.0) respectively. Most patients (min 70.0%, max 92.9%) had stable or improved VAS scores after treatment with KTE-X19.
Mean (SD) EQ-5D Index scores (US value set) were 0.82 (0.19) at screening with the highest score at Month 12 (0.91 [0.13]). Most patients had stable or improved EQ-5D Index scores after treatment with KTE-X19 (min: 57.5% [Day 28] max: 80.0% [Month 9]). Results were similar using UK, German, and French EQ-5D-5L index value sets. Based on MMRMs, estimated mean change in VAS exceeded clinically meaningful thresholds at Month 3 (mean [95% CI]: 9.6 [2.6, 16.5]), Month 6 (9.4 [2.5, 16.3]), and Month 12 (14.8 [7.0, 22.6]). Estimated mean change in EQ-5D-5L indices exceeded clinically meaningful thresholds at Month 12 (0.078 [-0.009, 0.164]) but confidence intervals overlapped 0. Similar to other patient outcome survey studies, results should be interpreted with caution due to missing follow-up data for some patients and small sample size.
Conclusion
Results showed that among R/R ALL patients participating in ZUMA-3, the majority of patients experienced improved or stable health-related quality of life as assessed by the EQ-5D scores, and this was more pronounced with the VAS score.
Keyword(s): B cell acute lymphoblastic leukemia, CAR-T, Quality of life, Relapsed acute lymphoblastic leukemia