TA872 · STA

Axicabtagene ciloleucel for treating diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma after 2 or more systemic therapies

Recommended for Cancer Drugs FundNovember 2018

Source documents

Final Appraisal DocumentAppraisal Consultation DocumentCommittee PapersScopeScope Consultation Comments

Intervention

axicabtagene ciloleucel (not stated)
genetically modified autologous T cell immunotherapy · chimeric antigen receptor T-cell therapy · intravenous

Conditions

diffuse large b-cell lymphomahaematology · relapsed_refractory
primary mediastinal b-cell lymphomahaematology · relapsed_refractory
transformed follicular lymphoma to diffuse large b-cell lymphomahaematology · relapsed_refractory

Clinical trials

TrialDesignPhasePivotal
ZUMA-1not statednot statedYes

Methodological decisions (3)

cost assumption

Uncertainty regarding intravenous immunoglobulin use; data from ZUMA-1 showed 8.3% of patients received IVIG, but committee believes real-world need remains uncertain. Data collection to determine proportion of patients requiring IVIG treatment in ZUMA-1 and through CDF access, and duration of treatment required.

ICER impact: uncertain_direction

survival extrapolation

Overall survival extrapolation methodology for axicabtagene ciloleucel; median OS not reached in ZUMA-1, requiring long-term extrapolation. Committee expects two-year and potentially five-year follow-up data to validate company's extrapolation choice and give more certainty to ICER estimates.

ICER impact: uncertain_direction

treatment sequencing

Uncertainty regarding convergence of progression-free survival and overall survival curves; two-year and three-year follow-up data anticipated to inform appropriate convergence assumption in cost-effectiveness modelling.

ICER impact: uncertain_direction

Evidence gaps

immature overall survival—Median overall survival had not been reached in ZUMA-1 at time of appraisal; long-term overall survival requires extrapolation. Five-year follow-up data anticipated in Q1 2022.
short follow up—Convergence of progression-free survival and overall survival curves uncertain; two-year and three-year follow-up data from ZUMA-1 anticipated to help inform timeline of convergence.
other—IVIG use in real-world setting uncertain; ZUMA-1 data showed only 8.3% patients received IVIG, but committee believes need for IVIG remains uncertain and should be resolved through further data collection.
immature overall survival—Median overall survival had not been reached in ZUMA-1 at the date of NICE appraisal; long-term overall survival had to be extrapolated over the time horizon of the cost-effectiveness model. Two-year follow-up data presented at ASH 2018, three-year follow-up potentially available in Q1 2020, and five-year follow-up data anticipated in Q1 2022.
other—Uncertainty regarding convergence of progression-free survival and overall survival curves; available two-year and three-year follow-up data from ZUMA-1 anticipated to help inform timeline of convergence.
other—Uncertainty regarding intravenous immunoglobulin (IVIG) use in real-world setting; while only 8.3% of patients in ZUMA-1 received IVIG, the committee believes need in real-world setting remains uncertain.

Commercial arrangement

managed access agreement · confidential · critical for recommendation

Special considerations

Cancer Drugs Fund eligible