TA895 · STA
Recommended for use within the Cancer Drugs Fund only. Limited to adults with DLBCL when an autologous stem cell transplant is suitable, if disease has relapsed within 12 months after first-line chemoimmunotherapy or is refractory to first-line chemoimmunotherapy. Conditions of managed access agreement must be followed.
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| salvage chemotherapy (50% r-ice and 50% r-gdp) followed by high-dose chemotherapy and autologous stem cell transplant | standard of care | Yes | — |
| standard care | standard of care | — | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| ZUMA-7 | RCT | III | Yes |
| ZUMA-1 | single_arm | — | — |
| JULIET | single_arm | — | — |
| SCHOLAR-1 | observational | — | — |
| ORCHARRD | RCT | — | — |
Economic model
ICER
Methodological decisions (14)
CAR T-cell therapy delivery costs in NHS
Company: bottom-up costing approach yielding £41,101 for first 100 days; concerns that NHS tariff not appropriate for HTA
ERG: concerned company approach likely underestimated true delivery costs; also concerned about transparency of NHS tariff
Committee: £41,101 delivery cost was acceptable; committee satisfied it captured reasonable projection of NHS costs
ICER impact: decreases
Autologous stem cell transplant costs
Company: £37,736 based on NICE NHL guideline inflated to 2020-21
ERG: preferred HRG-based cost of £17,181 as more transparent
Committee: company's estimate of £37,736 more appropriate and consistent with NHS practice
ICER impact: increases
Inclusion of retreatment costs for axicabtagene ciloleucel
Company: excluded retreatment costs as not part of marketing authorisation and unlikely to occur in practice
ERG: preferred to include retreatment costs to align modelled costs and benefits
Committee: agreed with ERG that costs and benefits should be aligned; concluded retreatment costs should be included
ICER impact: increases
Method to adjust standard care overall survival for treatment switching to CAR T-cell therapy
Company: used RPSFT model with full re-censoring; explored alternative censoring types and IPCW method
ERG: agreed RPSFT with full re-censoring was most appropriate but cautioned about remaining uncertainty
Committee: RPSFT model with full re-censoring was acceptable
ICER impact: decreases
Crossover adjustment needed to account for the use of third-line CAR T-cell therapy in ZUMA-7
ICER impact: uncertain_direction
Generalisability of ZUMA-7 results to NHS practice due to absence of chemotherapy bridging
Company: Not explicitly stated
ERG: Not explicitly stated in this chunk
Committee: Acknowledged the issues of generalisability to NHS practice (bridging chemotherapy used in 75% of NHS patients but not in ZUMA-7), which increases uncertainty. Concluded that collecting Cancer Drugs Fund data could reduce uncertainty
ICER impact: uncertain_direction
Generalisability of ZUMA-7 results to NHS practice regarding chemotherapy bridging
Company: not explicitly stated but trial design did not include chemotherapy bridging
ERG: noted lack of chemotherapy bridging in trial
Committee: acknowledged generalisability concern but noted Cancer Drugs Fund data collection could help resolve this
ICER impact: uncertain_direction
ZUMA-7 did not use chemotherapy bridging, which raised concerns about generalisability to NHS practice
ICER impact: increases
Concern about applying hazard ratio to mixture cure model; whether standard care should be disadvantaged after 5-year cure point
Company: applied proportional hazards assumption throughout extrapolation
Committee: concluded company's approach was acceptable but noted remaining uncertainty favourable to axicabtagene ciloleucel
ICER impact: uncertain_direction
Choice of parametric curve for extrapolating axicabtagene ciloleucel overall survival beyond trial follow-up
Company: Preferred generalised gamma distribution as it had good statistical fit and was validated by clinical experts
ERG: Preferred log-logistic curve as it had marginally better statistical fit and was more conservative given immature trial data
Committee: Concluded that both generalised gamma and log-logistic curves appeared plausible and agreed that the log-logistic model was appropriate given the uncertainty
ICER impact: decreases
Choice of parametric curve for axicabtagene ciloleucel overall survival extrapolation
Company: preferred generalised gamma distribution based on good statistical fit and clinical expert validation
ERG: preferred log-logistic curve due to marginally better statistical fit and more conservative extrapolation given immature trial data
Committee: log-logistic model agreed as appropriate given uncertainty about long-term survival
ICER impact: decreases
The distribution used to extrapolate overall survival for axicabtagene ciloleucel in ZUMA-7 was uncertain due to immature trial data
ICER impact: increases
Handling of subsequent third-line CAR T-cell therapy in standard care arm (56% of patients received this)
Company: Explored adjusting standard care overall survival to remove the benefit of subsequent CAR T-cell therapy using RPSFT model with full re-censoring
ERG: Not explicitly stated in this chunk
Committee: Agreed that adjustment was necessary because axicabtagene ciloleucel at 2+ lines had only been provisionally recommended and was not yet established practice
ICER impact: increases
Source of post-event utility values
Company: used ZUMA-1 (axicabtagene ciloleucel single-arm study) for pre-progression values
ERG: not explicitly stated but alternative would have been JULIET (tisagenlecleucel single-arm study)
Committee: accepted use of ZUMA-1 post-event utility values
ICER impact: negligible
Evidence gaps
Commercial arrangement
Special considerations
Cross-references