Cost Effective Analysis of Second Line Therapies in Relapsed Refractory Multiple Myeloma in Indian Scenario@ Indian Myeloma Congress, 2018Suman Kumar, Army Hospital (Research & Referral), New Delhi10 Feb 20171 / 37

Introduction2 / 37

Background

Incurable malignancy of plasma cells
Most patients diagnosed above 55 years
Chronic disease with multiple remissions and relapses
Negative impact on patient's overall health related QoL

3 / 37

Relapsed Refractory Multiple Myeloma

Improved survival in past 20 years (5 years survival 29.2% in 1992 to 50.2% in 2012)¹
It remains incurable with multiple relapses with multiple lines of treatment
Very poor prognosis with median OS of 9 months²
Recently Novel Agents approved for RRMM
- Pomalidomide (IMId)
- Daratumumab (anti CD 38 antibody)
- Carfilzomib (Proteosome Inhibitor)
- Panobinostat (HDAc inhibitor)
Major economic burden on individuals and society

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References

CAAC:CAAC21332
After previous reference

Parent Study

Christopher G. Pelligra, Kejal Parikh, Shien Guo et al.

Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed–refractory Multiple Myeloma in the United States

Clinical Therapeutics, Volume 39, Issue 10, 2017

http://www.sciencedirect.com/science/article/pii/S0149291817308998

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Conduct of study

Compared three protocols
- Pomalidomide-dexamethasone (POMd): MM-002 trial
- Single agent Daratumumab (DARA): SIRIUS trial
- Single agent Carfilzomib (CARF): PX-171-003-A1 trial
Multiple relapsed or refractory patients (Median previous therapies: 5)
Absence of head to head comparison trial
Matching adjusted indirect comparison done to get unbiased estimate of relative efficacy
Parametric fits were made for POMd arm of MM-002 data and HR were derived for DARA and CARF from their respective trials

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State diagram for outcomes

28 days cycles

7 / 37

Distribution of second line therapies (in %)

Initial Line
POM-d
DARA
CAR
LEN-d
BORT
THAL-d
PanVD


POM-d
0
7.5
38.4
22.2
17.8
6.6
7.5

DARA
40.2
0
24.8
14.4
11.5
4.3
4.8

CARF
50.2
6.0
0
18.0
14.4
5.4
6.0

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Initial Line	POM-d	DARA	CAR	LEN-d	BORT	THAL-d	PanVD
POM-d	0	7.5	38.4	22.2	17.8	6.6	7.5
DARA	40.2	0	24.8	14.4	11.5	4.3	4.8
CARF	50.2	6.0	0	18.0	14.4	5.4	6.0

Definitions of outcome measures

Progression free survival

Time from randomisation to disease progression (IMWG criteria) or death

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Definitions of outcome measures

Progression free survival

Time from randomisation to disease progression (IMWG criteria) or death

Post progression survival

Time from disease progression till death

9 / 37

Definitions of outcome measures

Progression free survival

Time from randomisation to disease progression (IMWG criteria) or death

Post progression survival

Time from disease progression till death

Fatal progression probability

Per cycle probability that a patient in PF state would die

9 / 37

Definitions of outcome measures

Premature treatment discontinuation

Time from randomisation till discontinuation of treatment prior to disease progression due to unacceptable toxicity, patient's preference or other reasons

10 / 37

Definitions of outcome measures

Premature treatment discontinuation

Time from randomisation till discontinuation of treatment prior to disease progression due to unacceptable toxicity, patient's preference or other reasons

Adverse Events

4 adverse events included (Grade 3/4, occuring in > 5% of patients on treatment)

Anemia
Fatigue
Neutropenia
Thrombocytopenia

Percentages converted to monthly incidence rates

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Utilities

Weights assigned to each state for calculating QALM lived

PF state: 0.7 to 0.76
PP state decrement: -0.084 to -0.025
AE decrement: -0.049 to -0.009

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Present Study12 / 37

Definitions and Assumptions13 / 37

Outcome parameters

All outcome parameters taken from the Parent trial
Adverse event parameters were derived from the percentages given in the original trials and converted into per cycle incidence rates
Fatigue was not considered as AE

14 / 37

Economic parameters

All costings were done with Jan 2018, which was taken as base time
All costings were converted to per cycle unit costs
Annual inflation rate of 3.5% to 6% was assumed
Annual discount rate of 3% was used

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Subclassification of costs

Regimen associated costs (= Regimen cost + Cost of adjuncts)
Cost of prophylaxis (VTE/Herpes) (= Cost of adjunct)
Cost of AEs (= PRBC txn + Plt txn + GCSF administration + 7 days of 3rd generation cephalosporin [10% of neutropenia])
Health care resource cost stratified according to health state (= Clinical Visits + CBC + Biochemistry + SPEP/SFLC/SIFE)

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Regimen related costs (per cycle)

Regimens
Variable Cost (INR), (unit)
Fixed Cost (INR) 


POM-d
-
20080.00

DARA (cycles 1-2)
2400.00, (per kg)
4200.00

DARA (cycles 3-6)
1200.00, (per kg)
2100.00

DARA (cycles > 6)
600.00, (per kg)
1050.00

CARF (cycle 1)
24675.30, (per sq m)
-

CARF (cycles 2-12)
26973.00, (per sq m)
-

CARF (cycles > 12)
17982.00 (per sq m)
-

LEN-d
-
15788.00

BORT
-
45200.00

THAL-d
-
7568.00

PAN-V-d (cycles 1-8)
-
110280.00

PAN-V-d (cycles > 8)
-
87640.00

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Regimens	Variable Cost (INR), (unit)	Fixed Cost (INR)
POM-d	-	20080.00
DARA (cycles 1-2)	2400.00, (per kg)	4200.00
DARA (cycles 3-6)	1200.00, (per kg)	2100.00
DARA (cycles > 6)	600.00, (per kg)	1050.00
CARF (cycle 1)	24675.30, (per sq m)	-
CARF (cycles 2-12)	26973.00, (per sq m)	-
CARF (cycles > 12)	17982.00 (per sq m)	-
LEN-d	-	15788.00
BORT	-	45200.00
THAL-d	-	7568.00
PAN-V-d (cycles 1-8)	-	110280.00
PAN-V-d (cycles > 8)	-	87640.00

Cost of Prophylaxis

VTE: (90% on Aspirin and rest on Enoxaparin) INR 1459.20
Antiviral: INR 360.00

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Cost of AEs (per episode)Anemia2 units of PRBC transfusion
INR 2100.00
Neutropenia5 days of GCSF transfusion and 7 days of 3rd generation cephalosporin (10% of neutropenia)
INR 5000.00
Thrombocytopenia1 unit of SDP/6 units of PRP
INR 1800.00
19 / 37

Health care resource utilisation cost (per cycle)

Headings
Unit Cost (INR)
PFS (T+)
PFS (T-)
PPS


Hematologist clinical visit
1000.00
2000.00
1000.00
3000.00

Full Blood Count
350.00
700.00
350.00
1050.00

Biochemistry (RFT/LFT)
1400.00
2800.00
1400.00
4200.00

SPEP
700.00
233.33
116.67
233.33

SIFE
5000.00
1666.67
833.33
1666.67

SFLC
6500.00
2166.67
1083.33
2166.67

Total
-
9566.67
4783.33
12316.67

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Headings	Unit Cost (INR)	PFS (T+)	PFS (T-)	PPS
Hematologist clinical visit	1000.00	2000.00	1000.00	3000.00
Full Blood Count	350.00	700.00	350.00	1050.00
Biochemistry (RFT/LFT)	1400.00	2800.00	1400.00	4200.00
SPEP	700.00	233.33	116.67	233.33
SIFE	5000.00	1666.67	833.33	1666.67
SFLC	6500.00	2166.67	1083.33	2166.67
Total	-	9566.67	4783.33	12316.67

Conduct of Study

(Computer simulation study)

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Sample Size

Horizon of 3 years was chosen for the simulation (stable economic condition). Patients were censored after 36 months.
100 patients for each of the 3 arms
Total of 500 simulations were done

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Few examples (POM-d arm)

23 / 37

Results24 / 37

Clinical Outcomes25 / 37

Median Overall Survival (months)

init_reg	mean_median_surv	95LCL	95UCL	25centile	75centile
pomd	17.1570	13.3333	21.3575	15.8512	18.4071
dara	17.0114	13.5000	21.0000	15.6667	18.3333
carf	16.7497	13.5000	20.6667	15.5000	18.0000

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Overall Survival at 3, 6, 12, 18, 24, 36 months

27 / 37

Median Progression Free Survival (months)

init_reg	mean_median_pfs	95LCL	95UCL	25centile	75centile
pomd	17.1425	13.3333	21.3575	15.8000	18.4000
dara	17.0007	13.5000	20.8812	15.6667	18.2708
carf	16.7488	13.5000	20.6667	15.5000	18.0000

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PFS at 3, 6, 12, 18, 24, 36months

29 / 37

Progression Free Life Months (PFLM)

init_reg	med_pfm	95LCL	95UCL	25tile	75tile
carf	4	3	4	3	4.0
dara	4	3	5	4	4.0
pomd	4	3	5	4	4.5

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Quality Adjusted Life Months (QALM)

init_reg	med_qalm	95LCL	95UCL	25tile	75tile
carf	11.0293	8.8127	13.7548	10.2393	11.9131
dara	11.2297	9.0112	13.7750	10.3453	12.1640
pomd	11.3767	8.9134	14.0928	10.5132	12.2253

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No difference in clinical efficacy between all three arms32 / 37

Economic Outcomes33 / 37

Regimen associated Discounted Cost

init_reg	med_cost_month	95LCL	95UCL	25tile	75tile
dara	55143.72	48638.94	63355.32	52726.57	57723.10
pomd	32370.84	21656.73	37982.45	29379.04	34890.15
carf	25769.79	23650.16	29015.03	24905.19	26911.36

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Cost per QALM

init_reg	med_cost_qalm	95LCL	95UCL	25tile	75tile
dara	86609.35	76026.52	99518.78	82721.20	90635.68
pomd	55897.85	44735.16	61518.81	51986.42	58222.93
carf	41495.18	37974.16	47988.91	40129.71	43575.42

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Conclusions

All the three treatment arms are equally effective clinically
Daratumumab has the highest median cost per QALM lived of INR 86609.00 (95% CI: 76027.00 - 99519.00). Incremental cost per QALM lived is INR 30711.00 than POM-d
Carfilzomib has the lowest median cost per QALM lived of INR 41495.00 (95% CI: 37974.00 - 47989.00). Incremental cost per QALM lived is INR (- 14403.00) than POM-d
Pomalidomide dexamethasone has the median cost per QALM lived of INR 55897.85 (95% CI: 44735.16 - 61518.81)

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Thank You37 / 37

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Cost Effective Analysis of Second Line Therapies in Relapsed Refractory Multiple Myeloma in Indian Scenario

@ Indian Myeloma Congress, 2018

Suman Kumar, Army Hospital (Research & Referral), New Delhi

10 Feb 2017

Introduction

Background

Relapsed Refractory Multiple Myeloma

References

Parent Study

Christopher G. Pelligra, Kejal Parikh, Shien Guo et al.

Cost-effectiveness of Pomalidomide, Carfilzomib, and Daratumumab for the Treatment of Patients with Heavily Pretreated Relapsed–refractory Multiple Myeloma in the United States

Conduct of study

State diagram for outcomes

Distribution of second line therapies (in %)

Definitions of outcome measures

Progression free survival

Definitions of outcome measures

Progression free survival

Post progression survival

Definitions of outcome measures

Progression free survival

Post progression survival

Fatal progression probability

Definitions of outcome measures

Premature treatment discontinuation

Definitions of outcome measures

Premature treatment discontinuation

Adverse Events

Utilities

Weights assigned to each state for calculating QALM lived

Present Study

Definitions and Assumptions

Outcome parameters

Economic parameters

Subclassification of costs

Regimen related costs (per cycle)

Regimen related costs (per cycle)

Cost of Prophylaxis

Cost of AEs (per episode)

Anemia

Neutropenia

Thrombocytopenia

Health care resource utilisation cost (per cycle)

Conduct of Study

Sample Size

Few examples (POM-d arm)

Results

Clinical Outcomes

Median Overall Survival (months)

Overall Survival at 3, 6, 12, 18, 24, 36 months

Median Progression Free Survival (months)

PFS at 3, 6, 12, 18, 24, 36months

Progression Free Life Months (PFLM)

Quality Adjusted Life Months (QALM)

No difference in clinical efficacy between all three arms

Economic Outcomes

Regimen associated Discounted Cost

Cost per QALM

Conclusions

Thank You

Introduction

Help