Take-aways:
- Pola-R-CHP is provisionally cost-effective when compared to R-CHOP for the frontline treatment of DLBCL.
- One-way sensitivity analysis demonstrated that pola-R-CHP is cost-effective up to a cost of $276,312 at a WTP threshold of $150,000.
- The cost-effectiveness of pola-R-CHP depends on its long-term outcomes.
Pola-R-CHP (polatuzumab, rituximab, cyclophosphamide, doxorubicin, and prednisone) can be more cost-effective than R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL) in cases where the efficacy benefit of pola-R-CHP is sustained long-term and the cost of subsequent chimeric antigen receptor (CAR) T-cell therapy remains high, according to a modeling analysis in a paper published in Blood.
However, the authors, led by Swetha Kambhampati, MD, of the Department of Hematology and Hematopoietic Cell Transplantation at the City of Hope National Medical Center in California, cautioned that pola-R-CHP was not cost-effective in many of the modeling iterations, “indicating there are clinical scenarios and health care settings where it may not be the cost-effective strategy.”
Polatuzumab vedotin, which is approved in combination with bendamustine and rituximab in relapsed/refractory DLBCL, is an antibody-drug conjugate composed of an anti-CD79b monoclonal antibody conjugated by a protease-cleavable linker to monomethyl auristatin E, a potent microtubule inhibitor.
In previous research comparing pola-R-CHP to standard R-CHOP, the phase III POLARIX trial demonstrated a 6.5% improvement in two-year progression-free survival (PFS) in DLBCL patients treated with pola-R-CHP, with no difference in overall survival or safety.
Markov Decision Process Model
Dr. Kambhampati and colleagues compared the cost-effectiveness of pola-R-CHP versus R-CHOP for DLBCL by using the TreeAge Pro 2021 software system to develop a Markov model (lifetime horizon) of a hypothetical cohort of U.S. adults (mean age, 65 years) with treatment-naïve DLBCL using a range of plausible long-term outcomes.
The researchers used the model to examine the impact of the two treatment regimens studied in the POLARIX trial: (1) R-CHOP, defined as six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and oral prednisone, followed by two cycles of rituximab for a total of eight cycles; and (2) pola-R-CHP, which consists of polatuzumab, rituximab, cyclophosphamide, doxorubicin, and oral prednisone for six cycles, followed by two cycles of rituximab.
For each treatment strategy, the simulated patients in the model transitioned among a set of health states, including remission, progression to relapsed/refractory DLBCL, remission after autologous hematopoietic stem cell transplant (HSCT), remission after CAR-T therapy, and death.
Simulated patients who achieved a complete or partial response after salvage chemoimmunotherapy proceeded to autologous HSCT in the next month, while patients without a response proceeded to CAR-T therapy.
The model’s transition probabilities and costs were identified from published literature and public data sources, and rates of remission, survival, and relapse for pola-R-CHP and R-CHOP were obtained from the POLARIX trial. The model assumed that the effectiveness of second- and third-line treatment for DLBCL was the same for pola-R-CHP and R-CHOP.
The costs of pola-R-CHP and R-CHOP were determined using the average wholesale price from Micromedex, and costs related to the drug, administration, adverse events, transplant and cellular therapy, and follow-up were also accounted for.
Pola-R-CHP Versus R-CHOP Cost-Effectiveness
Outcome measures were reported in incremental cost-effectiveness ratios (ICERs), assuming a willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life-year (QALY).
Assuming a five-year PFS of 69.6% with pola-R-CHP and 62.7% with R-CHOP, the researchers found that pola-R-CHP was cost-effective at a WTP threshold of $150,000 (ICER, $84,308/QALY). Pola-R-CHP was no longer cost-effective if its five-year PFS was 66.1% or lower.
When the researchers ran 10,000 Monte-Carlo simulations at a WTP threshold of $150,000, pola-R-CHP was the cost-effective strategy in 56.6% of the iterations.
One-way sensitivity analysis demonstrated that pola-R-CHP is cost-effective up to a cost of $276,312 at a WTP threshold of $150,000 (see TABLE 1 for more cost-effectiveness outcomes).
“Routine usage of pola-R-CHP would add significantly to health care expenditures,” the authors noted, adding that “price reductions or identification of subgroups that have maximal benefit would improve cost-effectiveness.”
Impact of CAR-T Costs
In addition to being dependent on its long-term outcomes, the cost-effectiveness of pola-R-CHP was also found to be dependent on CAR-T cost.
In the model, varying the cost of CAR-T therapy did not influence the cost-effectiveness of pola-R-CHP at a WTP threshold of $150,000, but at a WTP threshold of $100,000 per QALY, if CAR-T therapy costs were less than $281,663, pola-R-CHP would no longer be the cost-effective strategy, according to the paper.
This result suggests that the reason for frontline pola-R-CHP being cost-effective despite its substantially higher upfront cost is largely due to the high costs of subsequent CAR-T therapy for patients with relapsed/refractory DLBCL.
The study is limited by its use of estimated response, remission, and relapse rates from the POLARIX trial, which were used in the oncologic decision model process. In addition, long-term outcome data for pola-R-CHP are lacking. The study also only accounted for direct health care costs, and indirect costs such as absenteeism and productivity loss could further influence cost estimates.
“Assuming that PFS improvement with pola-R-CHP is maintained long-term (70% [five]-year PFS), it was the cost-effective treatment at a WTP [threshold] of $150,000 per QALY compared to R-CHOP,” the authors concluded. “Its cost-effectiveness was highly dependent on the [five]-year PFS and the reduction in the number of patients who need subsequent CAR-T therapy, which is associated with substantial costs.”
Reference
Kambhampati S, Saumoy M, Schneider Y, et al. Cost effectiveness of polatuzumab vedotin combined with chemoimmunotherapy in untreated diffuse large B-cell lymphoma. Blood. 2022. doi:10.1182/blood.2022016624