Glofitamab with Gemcitabine and Oxaliplatin Is Cost-Effective Versus Rituximab with Gemcitabine and Oxaliplatin for US Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Who Were Not Candidates for Autologous Stem Cell Transplant

Background:

The Phase III STARGLO trial (GO41944; NCT04408638) assessed glofitamab, a CD20xCD3 T-cell engaging bispecific antibody, in combination with gemcitabine and oxaliplatin (Glofit-GemOx) versus (vs) rituximab with gemcitabine and oxaliplatin (R-GemOx) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Enrolled patients had previously received 1 line of systemic therapy and were ineligible for autologous stem cell transplant (ASCT-ineligible) or had received ≥2 lines of systemic therapy. Fixed-duration Glofit-GemOx demonstrated a statistically significant and clinically meaningful benefit over R-GemOx in overall survival (OS; median: 25.5 vs 12.9 months; hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.43-0.88; descriptive p-value of 0.006) and progression-free survival (PFS) (median: 13.8 vs 3.6 months; HR: 0.40, 95% CI: 0.28-0.57; descriptive p-value of <0.001) (Abramson et al. EHA 2024). The aim of this analysis was to investigate the cost-effectiveness of Glofit-GemOx vs R-GemOx in patients with ASCT-ineligible R/R DLBCL, from a United States (US) payer perspective.

Methods:

A partition survival model was used to estimate lifetime quality adjusted life years (QALYs) gained, life years (LYs) gained, direct healthcare costs, and incremental cost-effectiveness ratios (ICERs) for Glofit-GemOx vs R-GemOx. Data from the STARGLO trial (Abramson et al. EHA 2024) were used to extrapolate clinical outcomes (OS, PFS, and duration of treatment) and to calculate dosing based on average patient characteristics. Direct healthcare costs included drug and administration costs, adverse event management, subsequent treatment, routine care and terminal care, and cytokine release syndrome monitoring costs. Drug costs were based on Medicare Average Sales Price (Q2 2024). Costs were calculated using publicly available unit cost data sourced from published literature and adjusted to 2024 US dollars. Future costs and benefits were discounted at an annual rate of 3%. A willingness to pay (WTP) threshold of $150,000 per QALY gained was applied as the threshold for demonstrating cost-effectiveness. Treatment effect on OS was assumed to be maintained throughout the patient's lifetime. However, if patients remained progression-free at 2 years, patient mortality in the model was matched to that of the general population, while quality of life (QoL) was reduced by 10% to account for additional comorbidities. The EuroQol 5-dimension 5-level questionnaire for QoL from the STARGLO trial was converted to utilities using US tariffs. Sensitivity analyses were conducted to assess the robustness of the results. A probabilistic sensitivity analysis (PSA) utilized 10,000 Monte Carlo simulations, and a one-way sensitivity analysis (OWSA) varied model inputs by ±20%.

Results:

When compared with R-GemOx, Glofit-GemOx was associated with an incremental cost of $197,848 and an improvement of 1.89 QALYs and 2.62 LYs, leading to an ICER of $104,756/QALY. The incremental cost was driven by increased treatment costs ($215,523), administration costs ($17,907), adverse event costs ($10,360) and supportive care costs ($6,299), and decreased progression-related costs (−$50,709) and terminal care costs (-$1,531). The OWSA found that the model was most sensitive to post-progression costs with R-GemOx, QoL in patients who progressed, and post-progression costs with Glofit-GemOx. When each input was varied in the OWSA, Glofit-GemOx remained cost-effective with ICERs ranging from $94,153 to $116,815/QALY. The PSA found that Glofit-GemOx was cost-effective in 80% of scenarios at a WTP threshold of $150,000/QALY.

Conclusions:

At a WTP threshold of $150,000/QALY gained, Glofit-GemOx was cost-effective compared with R-GemOx in patients with ASCT-ineligible R/R DLBCL, from a US payer perspective. Compared with R-GemOx, Glofit-GemOx was associated with increased LYs and QALYs and lower progression-related costs.

Fox:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. El Moustaid:F. Hoffmann-La Roche Ltd: Current holder of stock options in a privately-held company; Genentech/Roche: Current Employment. Masaquel:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current holder of stock options in a privately-held company. Rosettie:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; IQVIA, Inc.: Ended employment in the past 24 months; Genentech, Inc.: Current Employment. Celik:F. Hoffmann-La Roche Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Cassoli:Genentech, Inc.: Current equity holder in private company; Genentech, Inc.: Current Employment. Flowers:Guardant: Research Funding; Adaptimmune: Research Funding; Gilead: Consultancy, Research Funding; Acerta: Research Funding; Sanofi: Research Funding; Ziopharm National Cancer Institute: Research Funding; Xencor: Research Funding; Kite: Research Funding; AstraZeneca: Consultancy; BeiGene: Consultancy; Takeda: Research Funding; 4D: Research Funding; Bayer: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Pharmacyclics / Janssen: Consultancy; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Allogene: Research Funding; Genmab: Consultancy; Morphosys: Research Funding; Seagen: Consultancy; Eastern Cooperative Oncology Group: Research Funding; EMD Serono: Research Funding; Burroughs Wellcome Fund: Research Funding; Cellectis: Research Funding; Amgen: Research Funding; Nektar: Research Funding; Bio Ascend: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Research Funding; Pfizer: Research Funding; Celgene: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; BostonGene: Research Funding; Bristol Myers Squibb: Consultancy; Genentech/Roche: Consultancy, Research Funding; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; Novartis: Research Funding; Iovance: Research Funding; Spectrum: Consultancy; TG Therapeutics: Research Funding; Janssen Pharmaceuticals: Research Funding; AbbVie: Consultancy, Research Funding.