Stem cell transplantation continues to serve as a cornerstone treatment for multiple myeloma patients, maintaining its cost-effectiveness and accessibility despite the emergence of novel therapies including CAR T-cell therapy and bispecific antibodies, according to leading oncologists.
Dr. Mansi Shah, clinical director of multiple myeloma at Rutgers Cancer Institute, emphasized that stem cell transplant has withstood nearly four decades of attempts to replace it as a first-line treatment. "There have been multiple trials trying to knock it out for first-line treatment. However, they haven't been able to, so I still think it's an important tool that we have in our toolbox to treat multiple myeloma," Shah said.
Cost-Effectiveness Remains Key Advantage
The economic benefits of stem cell transplantation stand out particularly when compared to newer therapies. Shah noted that transplantation is "a very cost-effective therapy, especially if you look at how it compares to CAR T or other bispecifics and novel therapies. It's one and done, it's cheaper because it's been around for such a long period of time."
Dr. Harsh Parmar, associate professor of medicine at Hackensack University Medical Center, highlighted the significant cost differential, stating that "CAR T therapy can be as expensive as half a million dollars [and] some of the T-cell engager therapies are about the same; at least 1-year worth of T-cell engager therapy is about the same."
The cost advantage extends globally, with Shah pointing out that stem cell transplant serves as "the stronghold and the best treatment they have available for multiple myeloma" in low- and middle-income countries outside the US.
Novel Therapies Face Adoption Challenges
While CAR T-cell therapy and bispecific antibodies represent important advances, their widespread adoption faces significant barriers. Shah identified several challenges limiting bispecific uptake, particularly "the REMS [risk evaluation and mitigation strategy] and because of the cytokine release syndrome and the neurotoxicity potential during step-up dosing."
These safety requirements mean that the initial priming doses "are typically recommended to be done inpatient in a hospital setting," which has "limited uptake in the larger community" and rural settings.
The management of cytokine release syndrome (CRS) presents another obstacle. "Right now, it's a little bit vague. There are recommendations, but even the package inserts for the FDA-approved bispecifics don't really have a clear delineation about what to use when for the management of CRS," Shah explained.
Complementary Rather Than Competing Approaches
Rather than viewing these treatments as competing options, experts advocate for a complementary approach. Parmar emphasized that "rather than viewing 2 therapies as competing options, they should be viewed as therapies that complement each other."
This perspective is particularly important given that multiple myeloma remains incurable. "Myeloma continues to remain a cancer that we cannot cure, and keeping this in mind, overall survival, which represents the accumulation of all the progression-free survival that each therapy renders, relies on sequential administration of all these treatments," Parmar noted.
He warned that "eliminating stem cell transplant in preference of CAR T or T-cell engager therapy reduces available effective therapies, and that would eventually compromise the survival trajectory."
Future Considerations and Ongoing Research
Several clinical trials are currently investigating the optimal sequencing of these therapies, including CARTITUDE-6 comparing transplant to CAR T therapy in the front-line setting, and CARTITUDE-5 examining CAR T therapy in transplant-ineligible patients.
The potential movement of expensive therapies to first-line treatment raises significant cost concerns. Parmar explained that moving CAR T and bispecific therapies to newly diagnosed settings would affect "a significantly larger pool of patients," substantially increasing healthcare costs since "the cost burden is going to increase significantly in such a setting."
Shah suggested that outpatient administration of stem cell transplant at some institutions "allows people to continue to stay at home, reduces the hospital's costs as well as system-wide costs," further supporting its cost-effectiveness.
Both experts agreed that it would require "a therapy that gives people a cure to knock stem cell transplant out in the first-line setting," indicating that transplantation will likely maintain its important role in multiple myeloma treatment algorithms for the foreseeable future.
