San Diego, CA—New research from Canada supports the use of frontline therapy with bendamustine plus rituximab for patients with indolent B-cell non-Hodgkin lymphoma (NHL), reported Andrew Aw, MD, MEng, FRCPC, Division of Hematology, Ottawa Hospital, Ontario, Canada, at the 2016 American Society of Hematology meeting.
Based on the estimated cost, life expectancy, and quality-adjusted life-years (QALYs), the combination of bendamustine and rituximab was more cost-effective than the R-CHOP regimen (ie, rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone).
“Our model suggests that bendamustine plus rituximab is a cost-effective strategy for the frontline treatment of patients with indolent B-cell NHL as compared with conventional chemoimmunotherapy,” said Dr Aw. “Despite higher acquisition costs, the cost-effectiveness of bendamustine plus rituximab may be driven by the upfront advantage in progression-free survival. Our analysis supports the use of frontline bendamustine plus rituximab for indolent B-cell NHL in the Canadian setting,” he added.
Indolent or low-grade lymphomas, which are characterized by a chronic relapsing-remitting course, represent approximately 40% to 50% of all subtypes of NHL. Of the low-grade lymphomas, indolent B-cell NHL is the most common, comprising several different histologies.
“The current standard of care for the frontline treatment of indolent B-cell NHL is chemotherapy backbone coupled with rituximab, but the optimal choice of chemotherapy has not been clear as head-to-head trials comparing regimens have not demonstrated an overall survival advantage,” said Dr Aw.
In addition, although frontline chemotherapy is usually effective, disease relapse is common in indolent B-cell NHL, and subsequent lines of therapy often demonstrate decreasing efficacy, with lower quality remissions and shorter duration of responses than earlier lines of therapy.
“There is ongoing effort to investigate frontline strategies that may lead to improved clinical outcomes. The pan-Canadian Oncology Drug Review has recommended publicly funding bendamustine and rituximab on the basis of net clinical benefit, but concluded that uncertainty exists regarding the regimen’s cost-effectiveness,” Dr Aw said.
Bendamustine plus Rituximab versus R-CHOP
Dr Aw and colleagues developed a Markov model to estimate the cost, life expectancy, and QALYs associated with bendamustine plus rituximab versus the R-CHOP regimen as frontline treatment for advanced indolent B-cell NHL.
The analysis was performed from the Canadian healthcare system perspective, with a lifetime horizon (equivalent to 24 years) and with cycle lengths of 6 months.
Patients were administered frontline bendamustine plus rituximab or R-CHOP. Patients who responded to therapy received 2 years of maintenance rituximab and entered a disease progression–free state. On disease progression, patients received second-line chemotherapy with the regimen that had not been given initially.
Patients received a maximum of 3 lines of salvage therapy. The third salvage therapy was only permitted in age-appropriate patients who achieved at least 1-year remission from the second-line salvage therapy. Patients then entered a state of palliation for a maximum of 1 year before transitioning to the absorbent death state.
Bendamustine plus Rituximab More Cost-Effective Than R-CHOP
For the cohort receiving conventional R-CHOP therapy, the average costs (in Canadian dollars) and QALYs were projected as $116,811 and 5.86 QALYs, respectively.
For patients who received bendamustine plus rituximab, the average costs and QALYs were $121,364 and 6.38 QALYs, respectively. The incremental cost per QALY gained for bendamustine plus rituximab was $8812 with respect to R-CHOP.
For the historically accepted willingness-to-pay threshold of $50,000 per QALY, bendamustine plus rituximab was a more cost-effective strategy than R-CHOP 92% of the time in the entire cohort, said Dr Aw.
A subgroup analysis for each histology also demonstrated consistent results. Based on the willingness-to-pay threshold of $50,000 per QALY, bendamustine plus rituximab was the more cost-effective strategy than R-CHOP 66% of the time in follicular lymphoma, 82% in mantle-cell lymphoma, 64% in marginal zone lymphoma, and 86% in lymphoplasmacytic lymphoma.
Finally, in the sensitivity analyses, bendamustine plus rituximab remained cost-effective for each change in the variable explored. The model was most sensitive to changes in age at study entry, as well as the discount rate applied, but these observations did not change the interpretation of the results, said Dr Aw.