MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)
MRD negativity means no detectable myeloma cell among 100,000 or a million marrow cells. It is the best predictor of long survival and, since 2024, an accepted endpoint for accelerated approval.
Measured by next-generation flow (EuroFlow) or NGS (clonoSEQ) on bone marrow, increasingly with imaging (PET) confirmation. FDA ODAC voted 12-0 in April 2024 that MRD negativity at 12 months can support accelerated approval. Sustained MRD negativity (≥12 months) is the strongest prognostic marker; MRD-guided de-escalation of maintenance is being tested (DRAMMATIC, MASTER).
CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.
PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.
CARTITUDE-4 is the first randomised trial to show that a CAR-T improves survival in myeloma, and it moved cilta-cel into second-line use (FDA approval 2024). For patients whose disease returns after first-line lenalidomide, a one-off cell therapy now competes with continuous drug combinations. Capacity, cost and the need for bridging therapy still limit who actually receives it.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Pages like this
not linked directly; found by shared links- TargetCD38
Shares Multiple Myeloma Research Foundation (MMRF), MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma, CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint.
- ProductDaratumumab
Shares MRD-guided treatment-free intervals in myeloma, PERSEUS, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma.
- TermR-ISS / R2-ISS staging
Shares S. Vincent Rajkumar, Multiple Myeloma Research Foundation (MMRF), Multiple myeloma.
- PairingCD38 antibody added to PI-IMiD-dex (quadruplet induction)
Shares PERSEUS, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma, Multiple myeloma.
- ProductBortezomib
Shares PERSEUS, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma, CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint, CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy.
- ProductLenalidomide
Shares MRD-guided treatment-free intervals in myeloma, PERSEUS, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma.
- IdeaA dedicated clinic for people whose blood test says the cancer is back
Shares Dormant cells and minimal residual disease, Minimal / molecular residual disease (MRD), MRD / molecular residual disease testing.
- TermHigh-risk cytogenetics (myeloma)
Shares Multiple Myeloma Research Foundation (MMRF), Multiple myeloma.