An Alternate Day Dosing Strategy for Lenalidomide in Multiple
Myeloma Improves Cost-Effectiveness Whilst Maintaining Efficacy
Rakesh Popat1, Jenny Dickson2, Iftekhar Khan3, Simon Cheesman2, Laura Percy1, Sally Moore1, Shirley D'Sa2, Neil Rabin2 and Kwee Yong1
1UCL Cancer Institute, London, United Kingdom; 2University College London Hospitals NHS Trust, United Kingdom; 3Cancer Research UK & UCL Cancer Trials Centre, United Kingdom
Introduction
Results
Lenalidomide and dexamethasone is an established treatment regimen for patients with
· Demographics and efficacy analysis in comparison to MM009/010 trials (*Stadtmauer et
Modelled Time to Progression
One Way Sensitivity Analysis:
multiple myeloma.
al., 2009) are shown below:
using a Weibull Model
The recommended dosing schedule is 25mg daily for 21 days out of a 28 day cycle with
(scale parameter: =0.817 and =0.0276)
· Alter the following whilst all
Alternate Dosing
MM009/010
Demographic
Alternate Dosing MM009/010 trials
treatment continuing until disease progression.
Kaplan Meier (L+Dex)
others fixed:
Schedule
2 prior therapy*
Schedule
trials
L+Dex Predicted
Haematological toxicity is common and is managed as per SPC (see FDA website).
2 prior
· drug costs: +20%
Dex Predicted
The dose modification recommendations are summarised below:
therapy*
· mean TTP: -10% to +10%
Number of
39
220
Response rate (PR)
85% (33)
56.8%
· utility values: -5%
patients evaluable
If platelet count:
Recommendation
If neutrophil count
Recommendation
· Impact on ICER:
CR
3% (1)
11.8%
· range £23904 to £30047
Age, median
68yrs (37-85
63.1yrs
Fall to <30,000/mcL
Interrupt lenalidomide
Fall to <1000/mcL
Interrupt lenalidomide
(range)
treatment, follow CBC
treatment, add G-CSF,
VGPR
23% (9)
15.9%
weekly
follow CBC weekly
1 Prior line of
3
0
PR
59% (23)
29.1%
therapy, n (%)
(7.3%)
(0%)
Return to
Restart lenalidomide at Return to 1,000/mcL
Resume lenalidomide at
30,000/mcL
dose level 1
and neutropenia is the
25mg
2 prior lines of
36
220
MR
13% (5)
NS
only toxicity
therapy, n (%)
(87.8)
(100%)
Cost effectiveness Acceptability Analysis
SD
0% (0)
35%
Median lines of
2
NS
For each subsequent
Interrupt lenalidomide
Return to 1,000/mcL
Resume lenalidomide at
therapy, n (range)
(1-8)
Mean
Range
drop <30,000/mcL
treatment
and if other toxicity
dose level 1
PD
<1% (1)
0.9%
100
(Min - Max)
Return to
Resume lenalidomide at For each subsequent
Interrupt lenalidomide
Median number of
6
NS
d
Base case
£25281
30,000/mcL
5 mg less than the
drop <1000/mcl
treatment until recovery.
Median PFS/months
7.7
9.5
cycles, n (range)
(1-28)
olh 80
ICER
previous dose. Do not
Resume at next lower
(4.9-11.6)
res
Incremental
£31110
£18698 -
Median TTP/months
11.8
10.6
th
dose below 5 mg daily
dose level
Median duration
11.7
9.2
w
Cost (£)
£42245
o 60
of treatment/
(1-31.1)
(7.9-NR)
bel
Incremental
£1.29
0.026 - 7.6
months, n (range)
Median OS/ months
26.3
35.8
s
QALY
(24.4-NR)
tion
Methods
40
lau
ICER*
£24365
£3715 - >
Patients requiring
24
38%
Median follow-
9.1
51
msi
£100,000
Retrospective review of patients with relapsed MM treated in a single UK centre
dose reductions,
(62%)
up/months
of 20
Probability
Probability
n (%)
%
An alternate day schedule of lenalidomide was followed instead of the SPC schedule
Median duration of
7.1
13.0
cost-effective
cost-effective
response/ months
0
at £30000 =
at £40000 =
(see "Lenalidomide dose reduction schedule")
76%
82%
Actual drug costs were calculated by the number of capsules prescribed over the
0
20000
40000
60000
80000
Cost effectiveness
Threshold Cost / QALY (£)
treatment period based on the following costs per capsule (BNF + VAT):
* The ICER is very sensitive to incremental QALY. In some cases very small (as well as some very large) effects were possible which when divided by
25mg:
15mg:
10mg:
5mg:
Cost effectiveness analysis was based upon the evaluation of lenalidomide and
(incremental cost/ incremental QALY), yield very large ICERS. However, these cases were in < 2% of the simulations. Probability defined as the proportion of
simulated ICERS < a given threshold divided by total number of simulations
£249.60 ($389.77)
£226.80 ($354.28)
£216.00 ($337.41)
£204.00 ($318.59)
dexamethasone by the ERG for NICE
Comparison between the alternate day dosing schedule of lenalidomide and
This was compared to a predicted cost if dose modifications were performed using the
Conclusions
dexamethasone versus dexamethasome (excluding 20% VAT)
SPC schedule
The following assumption were made:
Lenalidomide dose reduction schedule and prices (including 20% VAT):
· In this limited retrospective study, we demonstrate that the alternate day
o The TTP and OS for the alternate day and the SPC schedule for patients at second
dosing schedule of lenalidomide is likely to have equivalent efficacy to the
Dose
SPC
Total
Cost/ cycle
Alternate
Total
Cost/cycle
Cost
and subsequent relapse were the same
standard schedule (MM009/010 trial patients at second relapse)
Level
Schedule
Dose/
day
Dose/
Saving
o Utility values to calculate the QALY for both lenalidomide schedules were the same
cycle
schedule
cycle
/cycle
o Additional costs such as monitoring and those incurred for adverse events were the
· There was a total saving of £464,322 ($725,704.64) which is equivalent to
Starting
25mg daily
525mg
£5,241.60
25mg daily
525mg
£5,241.60
same for both schedules
£11,905.69 ($18,607.81) per patient treated
1
15mg daily
315mg
£4,762.80
25mg alt
275mg
£2,745.60
£2,017.20
SPC Schedule
Alternate day
Cost Saving
· Cost effectiveness analysis estimated the Cost per QALY (ICER) to be
days
(GBP/ USD)
schedule
(GBP/ USD)
£25281 compared to the original Celgene submission (as recalculated by
(GBP/ USD)
All patients
£1,914,987.60
£1,450,665.60
ERG/ NICE) of >£47100
2
10mg daily
210mg
£4,536.00
15mg alt
165mg
£2,494.80
£2,041.20
£464,322.00
days
$2,991,859.90
$2,266,155.26
$725,704.64
· This ICER is comparable to the final NICE accepted Celgene submission
3
5mg daily
105mg
£4,284.00
10mg alt
110mg
£2,376.00
£1,908.00
Per patient
£49,102.25
£37,196.55
£11,905.69
days
(£24600) that included a price cap at 26 cycles and an increased QALY value
$76,714.37
$58,106.55
$18,607.81
for final years of life. Our model did not incorporate this.
Incremental
SPC Schedule vs Dex
Alternate Day Schedule vs Dex
· The ICER for this schedule is below the threshold of £20,000-£30,000 set by
Abbreviations:
NICE for drugs to be approved within the UK. Probability 76% at £30,000;
BNF: British National Formulae; ERG: Evidence Review Group; ICER: Incremental Cost-Effectiveness Ratio; NICE:
QALY
1.28
1.28
82% at £40000
National Institute For Health And Clinical Excellence; NR: Not reported; PFS: Progression Free Survival; QALY: Quality-
Adjusted Life Year; NR: Not reached; NS: Not Stated; SPC: Summary of Product Characteristics; TTP: Time To
Costs
£51705
£32360
Progression; VAT: Value Added Tax
· We recommend this schedule to be investigated prospectively
ICER (Cost/ QALY)
£40394
£25281
Conflict of Interests: There are no relevant conflicts of interest to disclose

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