What Is the Cost-Effectiveness of Obinutuzumab Plus Bendamustine Followed By Obinutuzumab Monotherapy for the Treatment of Follicular Lymphoma Patients Who Relapse after or Are Refractory to a Rituximab-Containing Regimen in the US?

Background. Obinutuzumab (G) was recently approved for the treatment of follicular lymphoma (FL) in patients who relapsed after or are refractory to a rituximab (R)-containing regimen. In the phase III open label GADOLIN study of patients with rituximab-refractory iNHL, patients received either bendamustine (B, 120 mg/m2, d1+2, c1-6) alone, or obinutuzumab (G 1000 mg (d1, 8, 15 c1, d1 c2-6) for up to six 28d cycles) plus B (90 mg/m2, d1+2, c1-6) followed by G monotherapy (100 mg every 2 mo for up to 2 years). The net clinical benefit and economic value of G+B vs. B in R-refractory patients and the larger relapse patient population have not been formally evaluated. The objective of this study was to estimate the cost-effectiveness of G plus B followed by G monotherapy vs. B monotherapy based on results of the phase III GADOLIN trial in rituximab-refractory FL patients as well as model results for a refractory/relapse population. Methods. We developed a Markov model that utilized the GADOLIN trial's progression-free (PFS), and pooled G+B and B post-progression survival (PPS) through 4.5 years to model long-term patient PFS, progression, and death. We fit parametric curves to trial PFS and PPS data; PPS was used in lieu of immature overall survival (OS) data to model transitions to death from the progressed state. We used a U.S. registry of FL patients to inform the PFS and OS curves beyond the trial follow-up time to reflect a refractory/relapse patient population. The National LymphoCare Study is a disease-specific, prospective registry that enrolled more than 2,700 patients with newly diagnosed FL from 2004 to 2007 from more than 200 practice sites in the U.S. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from the literature. Sensitivity analyses were conducted to assess uncertainty in the results. Results. Treatment with G+B followed by G monotherapy led to an increase in quality-adjusted life years (QALYs) relative to B-mono (1.23, 95% CR: -0.01, 2.38). The total cost of G+B was $114,815 and B-mono was $62,034, resulting in an incremental cost of $52,781. The average total cost was greater for G+B due primarily to increased drug and administration costs ($106,053 for G+B vs. $50,104 for B-mono), however this was offset by cost-savings for disease progression of -$4268 ($5,558 for G+B vs. $9,826 for B-mono). Adverse event costs were higher for G+B ($3,204) vs. B-mono ($2,103). The incremental cost-effectiveness ratio was $43,000 per QALY gained. In probabilistic sensitivity analyses, there was a 89% probability that G+B followed by G monotherapy was cost-effective versus B-mono at the $100,000 per QALY threshold. Conclusions. Our US-based analysis suggests that treatment with G+B followed by G monotherapy compared to B-mono is cost-effective in patients with FL who relapsed/refractory to a rituximab containing regimen. These findings are driven by the improvement in PFS with G+B treatment that lead to a projected increase in survival and decreased cost of treating disease progression. There was a high probability G+B was cost effective even when all parameters in the model were varied. In conclusion, G+B vs. B monotherapy in follicular lymphoma patients who relapse after or are refractory to a R-containing regimen is very likely cost effective in the US.