Abstract
Background
Two recently approved therapies for previously untreated chronic lymphocytic leukemia (CLL), (1) obinutuzumab (GA101) in combination with chlorambucil (G+Clb) and (2) ofatumumab in combination with Clb (O+Clb), have shown improved progression-free survival (PFS) versus Clb alone in two separate trials. However, their relative value has not been formally assessed. The objective of this study was to compare the cost-effectiveness of G+Clb versus O+Clb in previously untreated CLL patients, as well as conduct exploratory analyses versus other comparators.
Methods
Patient outcomes were simulated using a 3-state Markov model that included PFS, progression, and death. PFS parameters for G+Clb were fitted to the observed G+Clb trial (CLL-11 study) data, and a network meta-analysis incorporating the results of the O+Clb (COMPLEMENT 1 study) was used to estimate the relative treatment effect of G+Clb compared to O+Clb (progression HR = 0.34). Patient populations in these two trials were similar. Drug utilization, dosing and adverse events were incorporated based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs. One-way and probabilistic sensitivity analyses were conducted to assess the impact of data uncertainty on the results.
In an exploratory scenario analyses, we used similar methodology to estimate the cost-effectiveness of G+Clb versus rituximab plus bendamustine (R+B, progression HR = 0.41). A meta-regression on age was used to adjust for the age difference among the patient populations and indirectly taking into account different levels of comorbidities.
Results
Treatment with G+Clb led to an increase of 0.83 life years and 0.79 quality-adjusted life years (QALYs) relative to O+Clb. The total cost of O+Clb was higher by $3600 per patient relative to G+Clb. Higher G+Clb drug, administration, and adverse event costs were largely offset by lower progression costs compared to O+Clb. The incremental cost per QALY gained with G+Clb vs. O+Clb was $4,500. Based on probabilistic sensitivity analyses, there was a 99% probability that G+Clb was cost-effective compared to O+Clb at a societal willingness-to-pay threshold of $100,000 per QALY saved.
| Outcome . | G+Clb . | O+Clb . | Difference . |
|---|---|---|---|
| Average life years | 5.74 | 4.91 | 0.83 |
| Average QALYs | 3.95 | 3.16 | 0.79 |
| Total drug cost | $37,192 | $34,260 | $2,932 |
| Drug administration | $1,977 | $991 | $985 |
| Supportive care | $141 | $73 | $68 |
| Adverse events | $9,542 | $2,660 | $6,882 |
| Cost of progression | $46,861 | $54,147 | $(7,286) |
| Average total cost | $95,713 | $92,132 | $3,581 |
| Outcome . | G+Clb . | O+Clb . | Difference . |
|---|---|---|---|
| Average life years | 5.74 | 4.91 | 0.83 |
| Average QALYs | 3.95 | 3.16 | 0.79 |
| Total drug cost | $37,192 | $34,260 | $2,932 |
| Drug administration | $1,977 | $991 | $985 |
| Supportive care | $141 | $73 | $68 |
| Adverse events | $9,542 | $2,660 | $6,882 |
| Cost of progression | $46,861 | $54,147 | $(7,286) |
| Average total cost | $95,713 | $92,132 | $3,581 |
In the exploratory scenario analysis, G+Clb was $37,700 less expensive than R+B, and led to an increase of 0.67 QALY.
Conclusions
Our analysis suggests treatment with G+Clb compared to O+Clb is highly cost-effective based on indirect treatment comparison data. These results are driven by the improved PFS of G+Clb vs. O+Clb, as well as lower disease progression cost. Future direct comparisons of G+Clb versus other treatment options will further clarify the cost-effectiveness of G+Clb, and inform coverage and reimbursement policy decisions.
Reyes:Genentech: Employment, Equity Ownership. Off Label Use: Rituximab + Bendamustine in CLL. Gazauskas:Genentech: Consultancy. Becker:Roche: Employment. Moreno:Roche: Employment. Veenstra:Roche: Consultancy.
Author notes
Asterisk with author names denotes non-ASH members.
