Jichi Medical University

This study evaluated the cost-effectiveness of blinatumomab for adult Philadelphia chromosome-negative (Ph-negative) patients with B-cell acute lymphoblastic leukaemia (B-ALL) who were in measurable residual disease (MRD)-negative first remission, according to the ECOG1910 trial. A Markov model was created to compare the cost-effectiveness of four cycles of blinatumomab alternating with chemotherapy versus standard-of-care chemotherapy (SOC), in both Japan and the United States. The analysis was conducted over a lifetime horizon. Incremental cost-effectiveness ratios (ICERs) were calculated, with willingness-to-pay (WTP) thresholds set at ¥7 500 000 in Japan and $150 000 in the United States. A discount rate was set at 3%. In Japan, blinatumomab led to incremental costs of ¥27 472 739 and yielded 3.82 quality-adjusted life years (QALYs), resulting in an ICER of ¥7 193 601 per QALY. In the United States, incremental costs were $463 539 with 3.45 QALYs, yielding an ICER of $134 298 per QALY. When the 3-year progression-free survival (PFS) with blinatumomab was assumed as 80%, it was cost-effective unless the 3-year PFS for SOC exceeded 64.9% in Japan and 65.6% in the United States. Blinatumomab was less cost-effective for patients older than 51.6 years in Japan and 55.6 years in the United States. Blinatumomab is cost-effective as consolidation therapy for MRD-negative Ph-negative B-ALL patients, with sensitivity to age and PFS gains.

Elevated phosphate concentration in proximal tubular fluid promotes calcium phosphate microcrystallopathy, thereby accelerating the progression of chronic kidney disease (CKD). However, the clinical significance of proximal tubular phosphate exposure in humans remains uncertain. We aimed to determine whether estimated proximal tubular fluid phosphate concentration (ePTFp) is independently associated with age-related kidney function decline in adults with and without CKD. We conducted a 5-year prospective cohort study involving 308 adults with and without CKD. ePTFp-a novel, noninvasive index-and serum fibroblast growth factor 23 (FGF23) concentrations were derived from blood and urine measurements. Kidney function decline, expressed as estimated glomerular filtration rate (eGFR) slope, was modeled using linear mixed-effects analysis. Associations of ePTFp and serum FGF23 with eGFR slope were examined using multivariable regression analysis, adjusting for potential covariates at baseline, including age, sex, several comorbidities, current smoking status, eGFR, and urinary glomerular and tubular injury markers. Over 5 years, eGFR declined in participants with and without CKD, with a steeper decline in those with CKD. Higher baseline ePTFp and serum FGF23 were inversely correlated with eGFR slope. In multiple adjusted models, elevated ePTFp remained independently associated with faster eGFR decline, whereas the serum FGF23 association was attenuated after covariate adjustment. Elevated ePTFp was independently linked to accelerated kidney function decline, underscoring the clinical relevance of calcium phosphate microcrystallopathy. ePTFp may represent a practical biomarker with implications for prevention and treatment strategies targeting the aging kidney with proximal tubular phosphate exposure.