A cost-effective analysis shows that combined-modality therapy (CMT) is the preferred induction strategy over chemotherapy alone for younger patients with primary central nervous system (CNS) lymphoma.
“This strategy minimizes cost, while maximizing life expectancy and quality-adjusted life-years,” said lead investigator Anca Prica, MD, a hematology/oncology fellow at Sunnybrook Health Sciences Centre, Toronto, Canada.
Meanwhile, the preferred strategy for older patients is chemotherapy alone, Dr Prica said.
CMT using high-dose methotrexate and whole-brain radiotherapy is associated with improved response rates and a decrease in relapse rates compared with chemotherapy alone. The trade-off is a significant risk of delayed, treatment-related neurotoxicity, leading to significant morbidity and mortality. The rate of late neurotoxicity with CMT ranges from 26% to 100%, she said, with the risk of neurotoxicity being greater in older patients compared with those aged <60 years.
Dr Prica and her group performed a cost-effectiveness analysis comparing the 2 strategies, stratifying the analysis by age. The quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) were compared between the 2 strategies.
A Markov decision analytic model was used to compare CMT and chemotherapy alone for a hypothetical cohort of 60-year-old patients who were newly diagnosed with primary CNS lymphoma. Cohorts of patients aged <60 years and >60 years were analyzed. The model simulated the clinical course of patients over the course of 5 years.
The variables included response, relapse, and survival rates with CMT versus chemotherapy alone; the risk of developing neurotoxicity with each strategy; and the estimated survival once neurotoxicity develops. The model incorporated data on health state utilities, which were derived from a survey of expert physicians who manage patients with primary CNS lymphoma.
Resource utilization was based on clinical guidelines, the literature, and expert opinion. The direct costs were obtained from hospital, provincial, and national sources, as well as the literature, and were calculated in 2011 Canadian dollars. The indirect costs were estimated based on lost productivity using average wages in Canada. The costs and the effects were discounted by 5%.
All patients who received chemotherapy alone as induction therapy were assumed to have whole-brain radiotherapy on disease relapse. The benefit of having active disease was assumed to dominate any ill effects from neurotoxicity. The cost of living with neurotoxicity was assumed to be similar to living with Alzheimer’s dementia.
The quality-adjusted life expectancy was 1.55 QALYs for CMT versus 1.53 QALYs for chemotherapy alone. The ICER for the base-case CMT versus chemotherapy alone was $491,522 per life-year gained.
In patients aged <60 years, CMT yielded 2.44 QALYs compared with 1.89 QALYs for chemotherapy alone, corresponding to an expected benefit of 0.55 QALYs with CMT, or 6.6 quality-adjusted months. The CMT strategy dominated in younger patients, being $11,951 less expensive than chemotherapy alone.
There was no difference in QALYs between the strategies in patients aged >60 years. The chemotherapy- alone strategy dominated in the older group—it cost $11,244 less than CMT.
For younger patients, there were no threshold values for the cost of CMT or for the cost of managing severe neurotoxicity that would potentially lead to chemotherapy alone being favored, said Dr Prica. The model favored treating younger patients with CMT, unless the rate of neurotoxicity was more than 89% at 1 year, “a rate not encountered in the published literature.” Similarly, there were no circumstances under which CMT was favored for older patients.