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.

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Current fixed-duration CLL regimens are not MRD-guided, so the test result does not alter the treatment plan. While a negative result is prognostically favorable, its main clinical utility is to provide reassurance. A detectable result can cause unnecessary patient anxiety.

The field of multiple myeloma has transformed from having few treatments to an abundance of effective drugs. The primary clinical challenge is no longer finding a therapy that works, but rather determining the optimal sequence and combination of available options, highlighting a unique form of market maturity.

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.

An expert argues the path to curing metastatic cancer may mirror pediatric ALL's history: combining all highly active drugs upfront. Instead of sequencing treatments after failure, the focus should be on powerful initial regimens that eradicate cancer, even if it means higher initial toxicity.

The DREAM-7 trial showed a belantumab combination had an overall survival benefit versus a daratumumab regimen, a "premier drug" that previously changed the myeloma treatment landscape. This surprising result establishes a new, higher standard of care and positions belantumab as a top-tier therapy, not merely another option.

Unlike older IMiDs where T-cell effects are secondary, CELMoDs have a powerful, independent pro-T-cell mechanism. This dual action is so significant that in the future, CELMoDs will be prescribed not just for their direct anti-myeloma effects, but specifically to enhance the efficacy of T-cell therapies like CAR-T and bispecific antibodies.

An expert who initially viewed CELMoDs as incremental improvements now considers them fundamentally different. The new litmus test for future myeloma trials will be tracking prior patient exposure to CELMoDs like iberdomide, just as they track prior IMiD exposure today, cementing their status as a distinct therapeutic category.

The term "functional cure" is misleading and hinders progress. With one-third of heavily pretreated patients in the Cartitude 1 trial remaining disease-free for five years without maintenance, the data supports the classical definition of a "cure" used in other cancers. This semantic shift is crucial for advancing the field.

The dramatic efficacy boost from adding epcoritamab suggests it's the primary driver of patient benefit, not just an adjunct. This shifts the conceptual framework, positioning the bispecific antibody as the new therapeutic backbone, with rituximab and lenalidomide as supportive agents.