Menin inhibitors achieve high rates of MRD-negative remissions. However, the median duration is very short (4-6 months), suggesting current MRD assays may not adequately capture residual disease and that "MRD negativity" is not a reliable predictor of long-term benefit for this drug class.

The FLAG-IDA plus venetoclax regimen achieves very high MRD-negative remission rates. However, its similar efficacy in both frontline and first salvage settings suggests it might be more strategically deployed as a salvage therapy, avoiding its high toxicity in all patients upfront.

The Benefit study challenged the need for bortezomib in a modern quadruplet regimen. It found that adding bortezomib to an isatuximab-lenalidomide-dexamethasone backbone significantly improved response rates and sustained MRD negativity, confirming the proteasome inhibitor's ongoing, critical role even when using powerful new agents.

Minimal Residual Disease (MRD) negativity is now recognized by regulators as a surrogate endpoint in oncology. Because it is considered 'reasonably likely to predict progression-free survival,' this shift allows drug developers to use MRD data to support accelerated approval pathways, expediting the availability of new therapies.

As frontline therapies improve and create longer remissions, the first relapse becomes the pivotal moment for treatment. Experts advocate for treating this stage with the same intensity and goals as newly diagnosed disease, including aiming for MRD negativity.

Both experts advocate shifting immune cell engager use from late-stage, high-burden cancer to a minimal residual disease (MRD) setting. Treating a low tumor load maximizes the effector-to-target ratio, enhances efficacy, and significantly reduces side effects, potentially moving these therapies to first-line combinations.

Five-year follow-up from the CARTITUDE-1 trial suggests a potential cure for multiple myeloma is achievable. With roughly one-third of heavily pretreated patients remaining in remission at five years—and some confirmed as MRD-negative—the concept of a cure is now part of the operational discussion among specialists, a monumental shift for a disease long considered incurable.

A negative Minimal Residual Disease (MRD) result is not a universal surrogate for Progression-Free Survival (PFS). Its predictive power is context-dependent; it's meaningful when comparing similar treatments (e.g., BTKi + BCL2i vs. another BTKi + BCL2i), but less so when comparing entirely different drug classes.

In newly diagnosed, transplant-ineligible myeloma, an iberdomide-based triplet (Iber-Dara-Dex) achieved 64% MRD negativity. This result is described as "astounding" because achieving MRD negativity is not even a realistic goal for comparable IMiD-based triplets like Dara-Len-Dex (the MAYA regimen). This sets a dramatically higher efficacy bar for frontline treatments.