Drug developers have found a new shortcut in multiple myeloma: minimal residual disease, or MRD, now drives faster FDA approvals. Nathan Pennell, MD, PhD, FASCO, who leads Hematology and Oncology Medical Affairs at Bristol Myers Squibb, points out that MRD-negative complete responses have become the deepest benchmark for response in myeloma and tie directly to longer progression-free survival.
Therapies for multiple myeloma have kept patients alive and responding for years, but that success has slowed down clinical trials. Traditional endpoints like progression-free survival and overall survival take too long to show results. Pennell says this lag keeps new drugs out of reach for patients who need them quickly.
In August 2026, the FDA granted accelerated approval to the combination of iberdomide, daratumumab and hyaluronidase-fihj (Darzalex Faspro), plus dexamethasone for adults with multiple myeloma after at least one prior therapy, marking the first CELMoD approval based on MRD-negative complete response.
MRD as a Regulatory Shortcut
The FDA now accepts MRD-negative status as a surrogate endpoint, linking it to longer progression-free survival. This shift has already cleared the way for the first oral cereblon E3 ligase modulation (CELMoD) agent in myeloma, and more drugs are lining up behind it. The pace of new approvals has picked up. In the CancerNetwork clinical report, the EXCALIBER-RRMM trial showed a 41.1% MRD-negative complete response rate for the iberdomide-based combination, compared to 20.7% for the standard regimen of daratumumab, bortezomib, and dexamethasone. MRD was measured by next-generation flow cytometry at a sensitivity of 10-5.
Pennell makes it clear that this regulatory shortcut does not change daily practice. “You can prescribe the drug, and you can monitor patients with whatever clinical assays you would normally use in your practice,” he says. MRD testing is not required for routine care. It is a regulatory tool, not a new clinical rule. MRD-negativity only means the test did not detect disease at its sensitivity limit. It does not prove cure, as the OncLive expert assessment points out.
Medical Affairs and Real-World Evidence
Pennell’s medical affairs team at BMS looks beyond regulatory endpoints. They gather feedback from patients and clinicians to spot treatment gaps and barriers. When standard trials leave out certain groups—like patients with other health problems—Pennell’s group turns to real-world data and evidence generation trials. This approach helped BMS rethink its lung cancer strategy and better track unmet needs for the next decade.
Other oncology groups are moving in the same direction, using real-world evidence to include patient groups that were previously left out of advanced trials, as reported earlier.
The EXCALIBER-RRMM trial pre-specified both MRD-negative complete response and progression-free survival as dual primary endpoints, enabling assessment of both response depth and its clinical durability.
Editorial Perspective
MRD’s new role as a surrogate endpoint is changing how myeloma drugs reach patients. The FDA’s move to accept MRD for accelerated approval reflects the need to speed up access, since waiting for traditional endpoints can take years. Still, MRD does not change how doctors monitor patients. Regulatory innovation is moving faster than clinical routines. Drug makers can use surrogate endpoints to unlock approvals, but real-world care still depends on established clinical judgment. The next phase of oncology drug development will play out along this line.
