Comparing Outcomes of Autologous Stem Cell Transplant vs Bortezomob-Melphalan-Prednisone for the Treatment of Multiple Myeloma

Kathryn Maples, PharmD, BCOP, Winship Cancer Institute, Emory Healthcare, and Joseph Kalis, PharmD, BCOP, UCHealth Hematology/Oncology, UCHealth, highlighted the utilization of an early or delayed autologous stem cell transplant (ASCT) among patients with multiple myeloma (MM), as well as the role of the ASCT now that novel therapies such as daratumumab and carfilzomib are being introduced in the induction setting.

This presentation occurred at the Great Debates & Updates in Oncology Pharmacy 2022 meeting. 

In this study, Dr Maples and Dr Kalis analyzed the literature surrounding the utilization of ASCT for MM, aiming to choose an individualized therapeutic plan based on patient information and treatment guidelines for ASCT. They also sought to select prevention and monitoring strategies to address toxicities and optimize treatment outcomes associated with ASCT in MM. 

To understand the impact of minimal residual disease (MRD) negativity, the researchers performed a systematic review and meta-analysis that evaluated the prognostic value of MRD for progression free survival (PFS) and overall survival (OS) in a cohort of patients with MM. The team found that OFS significantly improved with MRD negativity across all disease settings.                                

MM is a rare, incurable malignancy that primarily effects the elderly patient population (median age at diagnosis is 69 years). In recent years, many novel therapies have been approved, which have improved the 5-year survival rate of patients with MM. 

This study focused on the use of melphalan-based autologous stem cell transplant for the treatment of MM at the consolidation period in newly diagnosed patients. Dr Maples described transplants as the “tried and true method” for newly diagnosed MM (NDMM), citing results from a study (the EMN02/H095 Study) comparing ASCT vs bortezomib-melphalan-prednisone (VMP) for intensification therapy in patients with NDMM. This study revealed that median PFS was significantly improved in the transplant arm when compared with VMP, and MRD negativity was higher in the transplant arm. Dr Maples cited results from the FORTE study, and the STaMINA Trial as well. 

“PFS is significantly improved with ASCT despite new therapies providing deep and durable responses” Dr Maples said, adding, “OS is not the most appropriate endpoint for frontline therapy in MM since this is an incurable disease and the goal of therapy is disease control, improved quality of life, and prolonged survival.” 

Dr Kalis argued that it may be time to move away from transplants. “Dr Maples and I will agree on the points that [when it comes to transplants] people with deeper responses do better, people with MRD negativity do better, and the role of consolidation is to improve depth of response,” he said. However, Dr Kalis notes that he and Dr Maples may differ when it comes to the importance of the depth of response vs how you get there. 

Dr Kalis argues that “myeloma is not a uniform disease, whereas stem cell transplant is a ‘one size fits all’ approach to treatment.”  He believes that myeloma’s complicated genomics call for personalized treatment, and personalized consolidation methods. 

In examining data from a study on whether MRD negative patients benefit from ASCT, Dr Kalis said that “in patients where the stem cell transplant upgraded their response, then there was an overall survival benefit,” adding, “however, patients in a complete response prior to transplant did not actually achieve a longer overall survival.” 

Dr Kalis compared CAR-T with deferred ASCT, claiming that after the first relapse, transplant shows an inferior response and similar PFS to CAR-T cell treatment, even after a patient’s had 4 to 5 relapses.” Regarding CAR-T consolidation, he believes CAR-T is a less toxic and effective alternative to ASCT to deepen response and achieve MRD negative outcomes, and MRD negative status can achieved in RRMM patients using upfront therapies and CAR-T.

“Currently, the treatment guidelines do not risk stratify and recommend different treatments based off of a patient’s risk status,” noted Dr Maples, adding, “but we are learning and know that myeloma is not a ‘one size fits all,’ and the approach could very well be different for different patients.” Dr Maples concluded that she thinks “we might be moving in the direction of a risk stratified approach where standard vs high risk patients might be treated differently, and the utilization of a frontline transplant may be different for those patients as well.”