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Low-Dose Nivolumab in Renal Cell Carcinoma: A Real-World Experience
Joseph J Zhao1, Nesaretnam Barr Kumarakulasinghe2,3, Vaishnavi Muthu2
1Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, jzhaozw@hotmail.com.
Background:
The approved doses of the single agent nivolumab - an anti-programmed cell death protein 1 (PD-1) monoclonal antibody - for renal cell carcinoma (RCC) are 3 mg/kg and a 240-mg flat dose, despite efficacy shown at lower doses in earlier CheckMate trials. In view of financial constraints, the minimum dose of nivolumab required for efficacy remains a critical area of inquiry.
Methods:
A retrospective review of RCC patients receiving single-agent anti-PD-1 treatment was conducted. Using the median cutoff of the maximum dose per body weight received, we investigated the effect of lower dosages on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse event-free survival (irAE-FS). Survival analysis was made by Kaplan-Meier, by uni- and multivariable Cox models, and by modeling the statistical interaction between dosages and survival.
Results:
32 patients were recruited: 8 patients (25%) receiving first-line treatment and 24 (75%) receiving second-line treatment and beyond. A median split at 2.15 mg/kg yielded 16 patients in both the lower-dose (LD) and the higher-dose (HD) cohort. Hazard ratios (HRs) demonstrated no difference in OS after adjustment for gender (HR = 0.22, 95% CI 0.05-1.05, p = 0.054; favoring LD), as well as in PFS after adjustment for gender and concurrent radiation therapy (HR = 0.58, 95% CI 0.25-1.34, p = 0.210; favoring LD). No differences in ORR were observed (50.0 vs. 43.8%, p = 1.00, in the LD and the HD cohort, respectively). Immune-related phenomena were observed in the LD group, including pseudoprogression and increased all-grade immune-related toxicities (irAE-FS: HR = 1.72, 95% CI 0.48-6.14, p = 0.293; favoring HD). Iterative dichotomization of dosages showed no dose-OS or dose-irAE-FS relationship.
Conclusion:
Our study suggests no apparent reduction in efficacy when using a low-dosage nivolumab regimen.
Insights
Lower doses of nivolumab (anti-PD-1) show comparable efficacy in renal cell carcinoma (RCC) patients. This study indicates that reduced nivolumab dosages do not compromise overall survival or progression-free survival, offering potential financial benefits.
Area of Science:
- Oncology
- Immunotherapy
- Renal Cell Carcinoma Research
Background:
- Approved nivolumab (anti-PD-1) doses for RCC are 3 mg/kg or 240 mg flat, despite evidence of efficacy at lower doses.
- Financial constraints necessitate investigating the minimum effective nivolumab dose for renal cell carcinoma.
Purpose of the Study:
- To evaluate the efficacy of lower-dose nivolumab in renal cell carcinoma (RCC) patients.
- To determine if reduced nivolumab dosages impact overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
Main Methods:
- Retrospective review of 32 RCC patients receiving single-agent anti-PD-1 therapy.
- Dosage comparison using a median split at 2.15 mg/kg into lower-dose (LD) and higher-dose (HD) cohorts.
- Survival analysis via Kaplan-Meier and Cox models, assessing OS, PFS, ORR, and immune-related adverse event-free survival (irAE-FS).
Main Results:
- No significant differences in OS or PFS between LD and HD nivolumab cohorts after adjustments.
- Objective response rates were similar: 50.0% in LD vs. 43.8% in HD.
- Increased immune-related adverse events (irAEs) were noted in the LD group, though not statistically significant.
Conclusions:
- Low-dosage nivolumab regimens appear to maintain efficacy in RCC patients.
- Further research may explore optimal dosing strategies balancing efficacy and toxicity.
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