ASCT as the Continued Standard of Care in Frontline Multiple Myeloma Therapy

At the 2023 Great Debates & Updates in Hematologic Malignancies Meeting in New York, New York, Amrita Krishnan, MD, FACP, City of Hope Comprehensive Cancer Center
Duarte, California, shared her insights into whether high-dose chemotherapy plus autologous stem cell transplantation (ASCT) after induction therapy should continue as standard-of-care frontline therapy for myeloma.

Dr Krishnan argued that that it should continue to be the standard of care. She participated in the debate with C. Ola Landgren, MD, PhD, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, who argued the opposing side. 

Transcript:

Hello, my name is Amrita Krishnan. I'm the director of hematology for City of Hope, Orange County, and also the director of the Judy & Bernard Briskin Center for Myeloma at City of Hope. My topic at Great Debates was the role of autologous stem cell transplantation as frontline therapy for myeloma.

I reviewed the DETERMINATION study, which was a study of early versus delayed transplant after RVD [lenalidomide, bortezomib, and dexamethasone] induction for newly-diagnosed patients with myeloma, which showed a progression-free survival advantage to the upfront use of transplant. 

I, then, talked about what are really validated endpoints as we make decisions for patients with myeloma and discussed should we use progression-free survival [PFS] or overall survival or MRD, and really made the point that looking at overall survival is challenging of myeloma, given that the median survival of standard risk patients with myeloma is over 10 years. To wait for that as our primary endpoint really is not something we should use for decision-making process. 

And to highlight that further, I looked at the GRIFFIN study, which was a dara-RVD [daratumumab-RVD] versus RVD induction, showing a PFS benefit to the quadruplet induction, but yet no overall survival benefit yet. So really, again, bringing back to the point that progression-free survival is a very valid endpoint. The DETERMINATION study met that endpoint. While quality of life in the transplant upfront had a deterioration during the transplant, it did recover to baseline.

Again, using quality of life should not be a factor in determining transplant versus no transplant, which I talked about second primary malignancies being the same in transplant versus no transplant in the DETERMINATION study. The flavor of second malignancies was different with more hematologic malignancy in the patient's undergoing transplant. 

And to that point, I do agree with some of Dr. Landgren's points that he made, that one size does not fit all, as we look to the future of myeloma therapy. Patient selection is important, so being able to better determine, for example, who is more at risk of secondary primary malignancies, may help us guide patients towards a transplant versus no transplant approach.  Risk stratification, so high-risk patients certainly seem to benefit the most from transplant and the use of quadruplet induction. I wanted to make the point that that doesn't obviate the need for transplant, because most of the trials using quadruplets were done in the context of transplant as consolidation therapy.

Source:

Krishnan A. Debate - Will ASCT Continue to Be the Standard of Care in Frontline Therapy? - Yes. Presented at the Great Debates & Updates in Hematologic Malignancies Meeting; April 13-15, 2023; New York, NY.