Cost-effectiveness of combination therapy of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone for previously untreated diffuse large B-cell lymphoma in Japan

Figures & data

Figure 1. Structure of the PartSA model. A partitioned survival analysis (PartSA) model was constructed with three health states: PFS, progressive disease (PD), and death. The model incorporated OS and PFS survival curves, and the proportion of patients in the PD state was calculated from the difference between the OS survival curve and the PFS survival curve. Abbreviations. PD, progressive disease; PFS, progression-free survival.

Table 1. Model inputs.

Variable	Base value	Range	Lower value	Upper value	Distribution	References
Patient characteristics
Age (years)	64	±4	60	68	Gamma	^14–16
Male proportion	57%	95% CI	55%	58%	Beta	^16
BSA (m^2)	1.60	±20%	1.28	1.92	Gamma	^16
Weight (kg)	56.9	±20%	45.5	68.3	Gamma	^16
Clinical outcomes
OS
Pola + R-CHP	Generalized gamma model (µ = 5.800, σ = 2.969, Q = −0.173)	—	—	—	—	POLARIX trial (June 2022 cut-off)
R-CHOP	Generalized gamma model (µ = 1.046, σ = 0.249, Q = −0.640)	—	—	—	—	POLARIX trial (June 2022 cut-off)
PFS
Pola + R-CHP	Generalized gamma model (µ = 2.087, σ = 1.100, Q = −0.365)	—	—	—	—	POLARIX trial (June 2022 cut-off)
R-CHOP	Generalized gamma model (µ = 0.459, σ = 0.285, Q = −0.905)	—	—	—	—	POLARIX trial (June 2022 cut-off)
SMR
Achieving PFS of 24 months	1.22	95% CI	1.09	1.37	Log-normal	^12
Progression within 24 months	2.42	95% CI	2.30	2.55	Log-normal	^12
General mortality	Japanese life-table	—	—	—	—	^13
Adverse events
Pola + R-CHP
Peripheral neuropathy
Grade 1 or 2	0.51	±20%	0.41	0.62	Beta	^6
Grade 3 or 4	0.02	±20%	0.01	0.02	Beta	^6
Diarrhea
Grade 1 or 2	0.27	±20%	0.22	0.32	Beta	^6
Grade 3 or 4	0.04	±20%	0.03	0.05	Beta	^6
Nausea
Grade 1 or 2	0.40	±20%	0.32	0.49	Beta	^6
Grade 3 or 4	0.01	±20%	0.01	0.01	Beta	^6
Febrile neutropenia
Grade 1 or 2	0.00	±20%	0.00	0.01	Beta	^6
Grade 3 or 4	0.14	±20%	0.11	0.17	Beta	^6
R-CHOP
Peripheral neuropathy
Grade 1 or 2	0.53	±20%	0.42	0.63	Beta	^6
Grade 3 or 4	0.01	±20%	0.01	0.01	Beta	^6
Diarrhea
Grade 1 or 2	0.18	±20%	0.15	0.22	Beta	^6
Grade 3 or 4	0.02	±20%	0.01	0.02	Beta	^6
Nausea
Grade 1 or 2	0.36	±20%	0.29	0.44	Beta	^6
Grade 3 or 4	0.00	±20%	0.00	0.01	Beta	^6
Febrile neutropenia
Grade 1 or 2	0	—	—	—	—	^6
Grade 3 or 4	0.08	±20%	0.06	0.10	Beta	^6
Costs (JPY)
Pola + R-CHP
Regimen cost/treatment cycle
Polatuzumab vedotin*	1,195,300	−15%	1,016,005	1,195,300	—	^23
Rituximab	142,930	—	—	—	—	^23
Doxorubicin	10,130	—	—	—	—	^23
Cyclophosphamide	3,030	—	—	—	—	^23
Prednisolone	1,000	—	—	—	—	^23
R-CHOP
Regimen cost/treatment cycle
Rituximab	142,930	—	—	—	—	^23
Vincristine	6,740	—	—	—	—	^23
Doxorubicin	10,130	—	—	—	—	^23
Cyclophosphamide	3,030	—	—	—	—	^23
Prednisolone	1,000	—	—	—	—	^23
Administration costs
Pola + R-CHP
First cycle	484,030	±20%	387,224	580,836	Gamma	^24
Subsequent cycles	148,575	±20%	118,860	178,290	Gamma	^24
R-CHOP
First cycle	478,810	±20%	383,048	574,572	Gamma	^24
Subsequent cycles	143,355	±20%	114,684	172,026	Gamma	^24
Follow-up
Month 1–3	1,414	±20%	1,131	1,696	Gamma	^24
After month 4	646	±20%	517	775	Gamma	^24
Treatment for adverse events
Peripheral neuropathy
Grade 1 or 2	0	—	—	—	—	—
Grade 3 or 4	3,241	±20%	2,593	3,890	Gamma	^23^,^24
Diarrhea
Grade 1 or 2	6,350	±20%	5,080	7,620	Gamma	^23^,^24
Grade 3 or 4	155,597	±20%	124,478	186,716	Gamma	^23^,^24
Nausea
Grade 1 or 2	12,085	±20%	9,668	14,502	Gamma	^23^,^24
Grade 3 or 4	236,085	±20%	188,868	283,302	Gamma	^23^,^24
Febrile neutropenia
Grade 1 or 2	0	—	—	—	—	—
Grade 3 or 4	267,172	±20%	213,738	320,606	Gamma	^23^,^24
Subsequent therapy after progression
Salvage chemotherapy
Average cost/regimen	2,944,421	±20%	2,355,537	3,533,305	Gamma	^23^,^24
Period (median PFS month)/regimen	5.2	Min to Max	3.7	6.7	Gamma	^5^,^25
ASCT
Average cost/patient	1,987,260	±20%	1,589,808	2,384,712	Gamma	^23^,^24
Intervention rate	0.25	±20%	0.20	0.30	Beta	^2
CAR-T therapy
Average cost/patient	35,342,023	±20%	28,273,618	42,410,427	Gamma	^23^,^24
Intervention rate	0.06	±20%	0.05	0.08	Beta	Expert opinion
End-of-life care cost/patient	2,900,000	±20%	2,320,000	3,480,000	Gamma	^26
Health-related utilities
PFS	0.82	95% CI	0.80	0.83	Beta	^17
PD	0.73	95% CI	0.69	0.77	Beta	^17
Decrement due to adverse events
Peripheral neuropathy
Grade 1 or 2	−0.39	±20%	−0.47	−0.31	Normal	^21
Grade 3 or 4	−0.64	±20%	−0.77	−0.51	Normal	^21
Diarrhea
Grade 1 or 2	−0.22	±20%	−0.26	−0.18	Normal	^22
Grade 3 or 4	−0.22	±20%	−0.26	−0.18	Normal	^22
Nausea
Grade 1 or 2	−0.20	±20%	−0.24	−0.16	Normal	^22
Grade 3 or 4	−0.20	±20%	−0.24	−0.16	Normal	^22
Febrile neutropenia
Grade 1 or 2	0	—	—	—	—	—
Grade 3 or 4	−0.47	±20%	−0.56	−0.38	Normal	^22
Discount rate	0.02	±0.02	0	0.04	—	^9

Abbreviations. ASCT, autologous stem cell transplantation; BSA, body surface area; CAR-T, chimeric antigen receptor T-cell; JPY, Japanese yen; OS, overall survival; PFS, progression-free survival; SMR, standardized mortality ratio.

*We estimated the drug cost of polatuzumab vedotin using a 30 mg vial without vial sharing.

Figure 2. Survival curves of base-case analysis. Parametric survival functions were fitted to the latest cutoff data of the POLARIX trial (as of June 2022) to predict long-term OS and PFS. Abbreviations. OS, overall survival; PFS, progression-free survival.

Table 2. Result of base-case analysis.

Costs and effectiveness	Discounted (2% per year)			Undiscounted
	Pola + R-CHP	R-CHOP	Difference	Pola + R-CHP	R-CHOP	Difference
Cost (JPY)
1st-line	10,045,328	2,997,594	7,047,734	10,160,533	3,080,795	7,079,737
Adverse events	53,738	30,921	22,817	53,738	30,921	22,817
Salvage chemotherapy	20,639,557	26,573,893	−5,934,336	26,498,207	33,782,925	−7,284,718
ASCT	383,524	399,267	−15,743	492,274	495,760	−3,486
CAR-T therapy	1,705,178	1,775,172	−69,993	2,188,688	2,204,188	−15,500
End-of-life care	2,090,560	2,112,467	−21,907	2,899,999	2,900,000	−1
Total	34,917,885	33,889,314	1,028,571	42,293,439	42,494,590	−201,151
Effectiveness (QALY)
PFS	9.05	8.03	1.02	11.17	9.85	1.32
PD	2.22	2.86	−0.64	2.85	3.63	−0.78
Adverse events	−0.02	−0.01	0.00	−0.02	−0.01	0.00
Total	11.25	10.87	0.38	14.00	13.46	0.53
Life years	14.11	13.73	0.38	17.57	17.02	0.55
ICER (JPY/QALY)			2,710,238			Dominant

Abbreviations. ASCT, autologous stem cell transplantation; CAR-T, chimeric antigen receptor T-cell; ICER, incremental cost-effectiveness ratio; JPY, Japanese yen; PD, progressive disease; PFS, progression-free survival; QALY, quality-adjusted life year.

Figure 3. Tornado diagram. The central vertical line in this tornado diagram represents the base-case value. An orange bar shows the result when the parameter uses an upper value, and a blue bar shows the result when the parameter uses a lower value. Abbreviations. BSA, body surface area; CAR-T, chimeric antigen receptor T-cell; INMB, incremental net monetary benefit; JPY, Japanese yen; PD, progressive disease; SMR, standardized mortality ratio.

Figure 4. Probabilistic sensitivity analysis results are plotted on a cost-effectiveness plane. The blue dot shows the ICER in the base-case analysis. The orange dots show the ICERs in 1,000 iterations of the probabilistic sensitivity analysis. The probability of Pola + R-CHP combination therapy being cost-effective was 99.2% (ICER < JPY7.5 million per QALY). Abbreviations. JPY, Japanese yen; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year.

Figure 5. Cost-effectiveness–acceptability curve. The blue line shows the probability of Pola + R-CHP combination therapy being cost-effective at the ICER value on the x-axis. The probability of Pola + R-CHP combination therapy being cost-effective was 99.2% when the reference value was JPY7.5 million per QALY. Abbreviations. JPY, Japanese yen; QALY, quality-adjusted life year.

Table 3. Results of scenario analyses.

Arm	Cost (JPY)	Difference	Effectiveness (QALY)	Difference	ICER (JPY/QALY)
Scenario 1: OS of Pola + R-CHP is equivalent to that of R-CHOP
Pola + R-CHP	32,341,878	−1,547,436	10.97	0.10	Dominant
R-CHOP	33,889,314		10.87
Scenario 2: SMR is adjusted by percentages of patients in the states of PFS and PD at 5 years
Pola + R-CHP	34,393,180	1,126,235	11.08	0.38	2,953,567
R-CHOP	33,266,944		10.70
Scenario 3: Utility values of the POLARIX trial are used
Pola + R-CHP	34,917,885	1,028,571	12.23	0.35	2,902,727
R-CHOP	33,889,314		11.87
Scenario 4: SMR in patients who progressed within 24 months is 5
Pola + R-CHP	33,091,456	2,073,978	10.67	0.59	3,518,953
R-CHOP	31,017,477		10.08
Scenario 5: Generic pricing is used
Pola + R-CHP	31,972,224	1,705,750	11.25	0.38	4,494,573
R-CHOP	30,266,474		10.87

ICER: incremental cost-effectiveness ratio; JPY: Japanese yen; OS: overall survival; PD: progressive disease; PFS: progression-free survival; QALY: quality-adjusted life year; SMR: standardized mortality ratio.

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