Comparative Analysis of Novel Versus Standard High-Cost Therapies: The Role of Autologous Stem Cell Transplantation for Mantle Cell Lymphoma in LMICs
Authors: Frutos Ortiz Cristobal Augusto , Enciso Arrua Maria Elvira , Paats Aline Nicole , Andino Neves Lidiane Katherine , Salinas Victor Ladislao , Ibarrola Dra. Milva , Malpica Castillo Luis Enrique , Valcarcel Bryan 
Published: December 2024

Background
For several decades, high-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) has been a valuable therapeutic option in the management of both malignant and non-malignant hematologic diseases. Despite ongoing issues with treatment access in low- and middle-income countries (LMICs), auto-SCT is generally recognized as a high-cost therapy, limiting its utilization in public and some private healthcare systems. For example, mantle cell lymphoma (MCL) remains largely incurable despite recent therapeutic advances, making auto-SCT a valuable consolidation strategy for fit patients. However, the role of auto-SCT in MCL has recently been questioned following the Triangle Study results. This study compared patients treated with standard chemotherapy plus auto-SCT and Rituximab maintenance (A arm) to those receiving standard chemotherapy plus two years of ibrutinib treatment (I arm). The results showed a trend towards better responses in the ibrutinib arm, particularly in high-risk patients with Ki67 over 30% and p53 over 50%. With the approval of novel drugs for the treatment of hematologic diseases, the paradigm of ‘high-cost’ therapies appears to be shifting away from SCT. Herein, we aim to evaluate the real-world cost of standard-of-care auto-SCT versus the use of a readily available BTK inhibitor at a large referral center in Paraguay.
Methods
We conducted a cost analysis focused on two treatment options: auto-SCT with the BEAM protocol versus ibrutinib therapy. Data were collected from the Central Hospital of the Instituto de Prevision Social (IPS) for patients who underwent auto-SCT from January 2021 to December 2023. Overall survival (OS) was estimated from diagnosis to death from any cause, while progression-free survival (PFS) was defined from diagnosis to relapse, progression, or death from any cause. We used the Kaplan-Meier method and Log-rank test to estimate survival probabilities.
Results
In the 5-years of the study period, a total of 42 patients with either Hodgkin (n=24) or non-Hodgkin lymphoma (n=18, 1 case with advanced NK T cell lymphoma) received auto-SCT as either consolidation (n=5) or upon relapse (n=37). The cost of auto-SCT in all these patients was determined to be $26,000 USD (range: $18,000 - $43,000 USD), noting that no transplanted patient required an ICU admission and that all patients received BEAM (with or without rituximab) as conditioning regimen. Of these patients, 7 had MCL and received auto-SCT as either consolidation at first remission (n=3) or upon relapse (n=4). With a median follow up of 24.3 months, the median OS and PFS of the 7 MCL patients were 29.1 months and 28.7 months with a 2-year PFS and OS of 83%, respectively; 2 patients with refractory disease that received auto-SCT after 2nd and 3rd line of therapy died after 30 months and 3 months of being disease free post SCT, respectively.
During the study period, the cost of ibrutinib was obtained from publicly available online data on hospital purchases. IPS purchased ibrutinib at $70 USD per capsule. Given current recommendations of during of therapy with ibrutinib of at least 2 years, the regimen of four capsules per day for 2 years (730 days) resulted in a total cost of $204,400 USD. The use of generic ibrutinib did not significantly reduce this cost, offering less than a 1% difference per capsule compared to the brand name. Considering these figures, it is approximately six times cheaper to offer patients auto-SCT for MCL as a consolidation strategy compared to two years of treatment with ibrutinib.
Discussion
The high cost of novel therapeutics, such as ibrutinib, poses significant challenges in LMICs, which already face difficulties with traditional high-cost treatments. While ibrutinib therapy is less toxic than auto-SCT, its cost limits accessibility. Despite the small sample size, the outcomes observed in MCL patients treated at our institution suggest that salvage SCT remains a viable and valuable rescue therapy for patients in LMICs. At a public health system level, the cost of treating one patient with ibrutinib could cover the cost of auto-SCT for approximately seven patients. This cost analysis highlights the need for cost-effective treatment strategies like auto-SCT in LMICs to maximize patient access to effective therapies.