Center for Outcomes Research and Economic
Evaluation for Health (C2H), National Institute of
Public Health (NIPH) | URL: http://c2h.niph.go.jp

March 31, 2021

[C2H1902] Summary of cost-effectiveness evaluation oftisagenlecleucel (Kymriah)
1. Indications
Relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL).
Relapsed or refractory CD19-positive diffuse large B-cell lymphoma (DLBCL).
2. Price of drug
Tisagenlecleucel was reimbursed from May 2019 for JPY 34,113,655 (as of March2021). The price was calculated by a cost-calculation method with a usefulness
premium of 35% (0.2 premium coefficient). This was designated as H3 costeffectiveness evaluation item.
3. Scope of cost-effectiveness evaluation
This product is used for CAR-T therapy. Continual injection is not needed. Patients
receive one dose of tisagenlecleucel. The scope of evaluation agreed upon at the firstsession of the Expert Committee of Cost-Effectiveness Evaluation (ECCEE) is
described hereafter. Inotuzumab is not indicated for patients younger than 15 yearsof age, and allogeneic hematopoietic stem cell transplantation (HSCT) is generally
not performed on elderly people. Based on these factors, the whole patient population
was categorized according to the age of the individuals.
(a) B-ALL
Patients up to 25 years of age with relapsed or refractory CD19positive B-ALL. Analyses should be performed for the following
Population

populations:(a) Patients up to 15 years of age(b) Patients from 15 to 25 years of age

Comparators(a) Blinatumomab ± allogeneic HSCT

(b) Blinatumomab ± allogeneic HSCT andInotuzumab ± allogeneic HSCT(b) DLBCL
Patients withPopulation

relapsedorrefractory CD19-positive DLBCL.

Analyses should be performed for the following populations:(a) Patients up to 70 years of age(b) Patients aged 70 years and above

Comparators(a) Salvage chemotherapy ± allogeneic HSCT(b) Salvage chemotherapy

4. Evaluation of additional benefits
According to the results of a systematic review, there are no randomized controlled
trials (RCTs) on the use of tisagenlecleucel in patients with B-ALL. Indirectcomparison was performed using pooled data from clinical trials (B2101J,ELIANA/B2202, and ENSIGN/B220). Based on these results, the ECCEE judged thattisagenlecleucel has additional benefits over the comparators for B-ALL.
Similarly, the results of systematic review revealed that there are no RCTs
on the use of tisagenlecleucel in patients with DLBCL. Indirect comparison wasperformed using the data from the single-arm JULIET trial. Based on the results ofindirect comparison, the ECCEE also agreed that tisagenlecleucel has additional
benefits over the comparators for DLBCL.
5. Result of cost-effectiveness analysis
The manufacturer calculated the cost-effectiveness using a partitioned survival modelbased on the data obtained from clinical trials. On the contrary, the academic
technology assessment group identified the following issues:
・ There were certain methodological issues with the approach that was used forextrapolating the survival curve, and it caused an overestimation of the prognosisof tisagenlecleucel.
・ During the analysis for DLBCL, the starting age in the model used by themanufacturer was decided by the age of the patients in the clinical trial. However,
the age was found to be lower than the actual age of the patient population.
・The QOL score of the patients with remission was found to be high during analyses
for DLBCL.
・ Estimating the effectiveness of tisagenlecleucel in the population (b) with DLBCLusing the very small sample data of the JULIET trial was inappropriate, as patients
less than 70 years had been excluded, and the uncertainty was high.
The

academicgroup

revisedtheeconomicmodel

based

on

theaforementioned issues, and re-calculated the results. The results were submitted
to the third session of the ECCEE and were approved. The final results obtained foreach population are provided hereafter.
Population

Comparators

ICER (JPY/QALY)

Blinatumomab ± allogeneic HSCT

2,184,285

Blinatumomab ± allogeneic HSCT

2,571,736< 25 years

Inotuzumab ± allogeneic HSCT

2,747,550

aged < 70

Salvage chemotherapy ±years

allogeneic HSCT

aged < 15years
B-ALL

aged >=15andDLBCL

aged >= 70
years

Salvage chemotherapy

USD 1 = JPY 105, and EUR 1=JPY 126 (as of March 2021)

8,084,464
12,538,653