TA874 · STA
Recommended for untreated DLBCL with an IPI score of 2 to 5, only if the company provides it according to the commercial arrangement
Source documents
Intervention
Condition
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| r-chop | active drug | Yes | Yes |
| r-chp | active drug | Yes | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| POLARIX | RCT | phase 3 | Yes |
| GOYA | RCT | phase 3 | — |
Economic model
ICER
Methodological decisions (16)
Patient weight distribution to use for vial costing. Trial population mean weight 75.92 kg lower than NHS Health Survey (78.75 kg).
Company: Weight from full POLARIX population (75.92 kg) appropriate; supported by O'Brien et al. showing 5% weight loss in DLBCL patients at diagnosis
ERG: O'Brien et al. population not generalisable to NHS DLBCL patients
Committee: Weight from Western subgroup of POLARIX (80.1 kg) more generalisable to UK population than full trial; unconvinced by weight loss assumption
ICER impact: increases
Progressed disease supportive care costs estimation
Company: Updated approach based on survey of 3 clinicians about second-line treatment resource use; applied same costs every weekly cycle
ERG: Company's approach assumes indefinite supportive care costs; should account for response to subsequent treatments and periods of lower intensity follow-up; estimated 50% reduction in company costs was appropriate based on time to progression estimates
Committee: Company costs likely overestimated; appropriate reduction is between 25% to 50%, with 30% used in final base case
Company's progressed disease supportive care costs likely overestimated; ERG assumed 50% reduction which was likely underestimate
Company: Original progressed disease costs
ERG: 50% reduction in progressed disease costs
Committee: Reduction in progressed disease costs by between 25% to 50% (updated base case used 30%)
ICER impact: decreases
Technical error in progression-free survival modelling where PFS capped to OS extrapolation. Company made correction but appropriateness unclear.
Company: Correction ensures PFS does not exceed OS by capping at OS extrapolation
ERG: Correction provides counter-intuitive results and inflexible model; unable to adequately scrutinise validity
Committee: Unclear if correction appropriate; issue remained uncertain despite company clarification
ICER impact: uncertain_direction
Economic model structure for cost-effectiveness analysis
Company: Used 3-state partitioned survival model with health states: progression-free, progressed disease, and death
Committee: Partitioned survival model is standard for cancer drugs and appropriate
Whether to include IPI 0-1 population. Company provided evidence only for IPI 2-5, excluding IPI 0-1.
Company: Restrict to IPI 2-5 as trial excluded IPI 0-1
Committee: Exclude IPI 0-1 as appropriate in line with trial evidence; IPI 0-1 has good outcomes and small proportion of DLBCL population
ICER impact: uncertain_direction
Patient weight distribution from trial vs NHS population
Company: Initially used full POLARIX population weight (75.92 kg); later argued Western subgroup weight (80.1 kg) and applied 5% weight loss assumption based on O'Brian et al. study suggesting generalisability to full population
ERG: Noted O'Brian et al. was done in a non-generalizable population to NHS DLBCL patients
Committee: Western subgroup weight distribution (80.1 kg) is most likely generalizable to NHS DLBCL population; rejected the 5% weight loss assumption based on single non-generalizable study
Committee preferred to consider full POLARIX population rather than IPI 3-5 subgroup scenario analysis
Company: Provided scenario analysis for IPI 3 to 5 subgroup
Committee: Full POLARIX population
ICER impact: uncertain_direction
Use of mixture-cure model to extrapolate progression-free and overall survival. Overall survival informed by progression-free survival due to immature overall survival data.
Company: Use mixture-cure model with overall survival informed by PFS; assume continued OS benefit and no waning
ERG: Overall survival extrapolations highly uncertain; applied treatment waning to account for uncertainty and subsequent treatments
Committee: Mixture-cure model is reasonable; company approach more clinically plausible than applying waning to cured population
ICER impact: decreases
Uncertainty about the appropriateness of the company's correction to progression-free survival modelling where PFS is capped to match/not exceed OS extrapolation
Company: Corrected the model to cap PFS extrapolation at the point it would meet or exceed OS extrapolation
ERG: Raised concerns that the correction provides counter-intuitive results and the mixture-cure model is inflexible to such changes; unable to adequately scrutinise the correction
Committee: Unclear if the company's correction was appropriate; acknowledged the correction lowered the ICER
Company included progression-free survival curve correction after consultation; unclear if appropriate and lowered ICER
Company: Included PFS curve correction
Committee: Removal of the progression-free survival curve correction in updated base case
ICER impact: increases
Whether treatment effect for overall survival diminishes over time. Company argues no waning appropriate for curative intent disease; ERG applied waning to account for uncertainty and subsequent treatments.
Company: No waning effect; DLBCL is curable in first line
ERG: Applied waning equal OS in each arm after 60 months to account for uncertainty and subsequent treatments
Committee: No treatment effect waning; company approach more clinically plausible despite uncertainty
ICER impact: decreases
Whether treatment effect wanes over time
Committee: No treatment effect waning assumed
Inclusion of CAR-T therapies as subsequent treatments
Company: Initially included CAR-T therapies (axicabtagene ciloleucel and tisagenlecleucel) as subsequent treatments; agreed to remove them after technical engagement
ERG: CAR-T therapies are not routinely commissioned; should not be included; when removed, did not redistribute CAR-T use to other treatments (resulting in 97% subsequent treatment use)
Committee: CAR-T therapies should not be included; redistribution of CAR-T therapy use to other subsequent treatments is acceptable and appropriate
Source of utility values for progressed disease state
Company: Used GOYA trial utility values because of longer follow-up than POLARIX; noted some POLARIX progressed disease patients did not report HRQoL and those who did had better outcomes; timing of GOYA data collection not disclosed
ERG: Agreed with GOYA utility values as similar to TA649; applied age adjustment using UK general population utilities from Ara and Brazier 2010
Committee: GOYA utilities acceptable for decision making but uncertain; would have preferred data collected after second-line treatment; noted toxicity of later line treatments would affect quality of life
Utility values for progressed disease were uncertain but approach in base case was acceptable
Committee: Base case approach acceptable for decision making
ICER impact: negligible
Evidence gaps
Commercial arrangement
Special considerations
Cross-references