ADVANCE Trial Aims to Modernize Frontline Multiple Myeloma Care: Ola Landgren, MD, PhD

In part 1 of an interview with The American Journal of Managed Care®, Ola Landgren, MD, PhD, chief of the myeloma division and leader of the experimental therapeutics program at Sylvester Comprehensive Cancer Center, discusses the background and primary objective of the ADVANCE trial (NCT04268498), which evaluated carfilzomib-lenalidomide-dexamethasone with or without daratumumab in patients with newly diagnosed multiple myeloma.

Landgren, the study's lead investigator, is set to present the findings on Sunday, June 15, during the session "Treatment of Newly Diagnosed Multiple Myeloma (NDMM)" at this year's European Hematology Association Congress in Milan, Italy.

This transcript was lightly edited; captions were auto-generated.

Transcript

Prior to the ADVANCE clinical trial, what was known about the impact of modern combination therapy on outcomes for patients with newly diagnosed multiple myeloma?

Prior to the ADVANCE clinical study—that is an investigator-initiated study for [patients with] newly diagnosed multiple myeloma, it's a multicenter randomized study using carfilzomib-lenalidomide-dexamethasone with or without Darzalex or daratumumab—we have seen most of the studies up to now using the backbone of bortezomib-lenalidomide-dexamethasone, with or without daratumumab. Also, we have seen studies using either bortezomib- lenalinomide-dexamethasone, with or without isatuximab, or carfilzomib-lenalidomide-dexamethasone with isatuximab.

But we have not seen prior randomized studies using carfilzomib-lenalidomide-dexamethasone with or without Darzalex or daratumumab, so that's a new piece of information going forward. Given that daratumumab, in particular, here in the United States, is very, very commonly used, this is a very important piece of information.

I should say that the ADVANCE clinical trial uses minimal residual disease [MRD] detection as the primary end point after 8 cycles of therapy. Patients could go on this study...—it was open for enrollment when it was ongoing, for enrollment for patients [who] were both transplant eligible, transplant ineligible, and transplant deferred. All groups of patients that are newly diagnosed could go on the trial, and we could then look for the primary end point, being MRD negativity.

After 8 cycles of combination therapy, patients [who] were MRD negative went straight to maintenance therapy with deferred, delayed transplantation, if they collected stem cells. They did not do the transplant, if they were MRD negative. For patients [who] were transplant eligible [and who] had collected their stem cells, if they were MRD positive, transplant was recommended, and then [they would] go into maintenance.

This is a modern study in very many ways. It uses MRD as a primary end point. It's also open for all categories and allows patients [who] are MRD negative to go straight to maintenance. It has a lot of different details that are, I would say, quite future-looking and pushing the envelope forward.

Can you elaborate on the primary aim of the ADVANCE clinical trial and the methods used to investigate it?

In the ADVANCE clinical trial, the primary end point was minimal residual disease negativity using next-generation sequencing by the adaptive clonoSEQ assay. This was done after 8 cycles of combination therapy.

The threshold to determine success was calibrated at 10-5—1 in 100,000, which is aligned with the FDA definition of MRD negativity. Also, here in the United States, the NCCN [National Comprehensive Cancer Network] guideline and also the International Myeloma Working Group criteria.

Secondary end points include a lot of certifications, looking at MRD in older and younger patients by high-risk or standard-risk cytogenetics. Also, looking at 10-6 and sustained MRD negativity in many other flavors of MRD, but 10-5 after 8 cycles of combination therapy, that was the primary endpoint in the intention-to-treat population.