Personal view on future management of newly diagnosed patients with HR MM
| Newly diagnosed transplant-eligible (NDTE) patients with MM . | ||
|---|---|---|
| Risk (estimated frequency) . | Definition . | Suggested treatment . |
| HR (≤40%) | ISS 3, 1 cytogenetic-molecular aberration as listed*, R-ISS 3, R2-ISS 3 and 2 intermediate-high, circulating PCs†, EMD, PCL‡ | Quadruplet induction (MoAb + PI + IMiD + dex) Double ASCT Quadruplet consolidation Two-drug maintenance (PI + IMiD) for ≥2-3 y if sustained MRD− |
| If persistent MRD positivity after optimal quadruplet-based induction followed by ASCT | Consider switching treatment to consolidation therapy including novel classes of currently investigational drugs (eg, CELMoDs) combined with anti-CD38 MoAb or treatment intensification with innovative investigational immunotherapies, including CAR T cells or bispecific T-cell engagers (if available) at the time of conversion from MRD− to MRD+ | |
| Newly diagnosed non-transplant-eligible (NDNTE) patients with MM | ||
| Fit patients | Same HR definition as per NDTE | Quadruplet induction (MoAb + PI + IMiD + dex) therapy followed by 2-drug (IMiD + PI) or 3-drug (MoAb + IMiD + PI) maintenance until PD, or for at least 2-3 y if sustained MRD−. Consider switching treatment from 2-drug to 3-drug maintenance therapy, or from 3-drug to novel classes of currently investigational drugs (eg, CELMoDs) combined with anti-CD38 MoAb as maintenance, or to innovative investigational bispecific T-cell engagers, if available, in patients with persistent MRD+ after at least 6 mo of maintenance therapy. In MRD− patients, consider close MRD assessment during maintenance and switching therapy, if available, at the time of conversion from MRD− to MRD+. |
| Frail patients | IMWG definition | Dose-adjusted triplet or doublets Dex-sparing regimens or quick dex held |
| Newly diagnosed transplant-eligible (NDTE) patients with MM . | ||
|---|---|---|
| Risk (estimated frequency) . | Definition . | Suggested treatment . |
| HR (≤40%) | ISS 3, 1 cytogenetic-molecular aberration as listed*, R-ISS 3, R2-ISS 3 and 2 intermediate-high, circulating PCs†, EMD, PCL‡ | Quadruplet induction (MoAb + PI + IMiD + dex) Double ASCT Quadruplet consolidation Two-drug maintenance (PI + IMiD) for ≥2-3 y if sustained MRD− |
| If persistent MRD positivity after optimal quadruplet-based induction followed by ASCT | Consider switching treatment to consolidation therapy including novel classes of currently investigational drugs (eg, CELMoDs) combined with anti-CD38 MoAb or treatment intensification with innovative investigational immunotherapies, including CAR T cells or bispecific T-cell engagers (if available) at the time of conversion from MRD− to MRD+ | |
| Newly diagnosed non-transplant-eligible (NDNTE) patients with MM | ||
| Fit patients | Same HR definition as per NDTE | Quadruplet induction (MoAb + PI + IMiD + dex) therapy followed by 2-drug (IMiD + PI) or 3-drug (MoAb + IMiD + PI) maintenance until PD, or for at least 2-3 y if sustained MRD−. Consider switching treatment from 2-drug to 3-drug maintenance therapy, or from 3-drug to novel classes of currently investigational drugs (eg, CELMoDs) combined with anti-CD38 MoAb as maintenance, or to innovative investigational bispecific T-cell engagers, if available, in patients with persistent MRD+ after at least 6 mo of maintenance therapy. In MRD− patients, consider close MRD assessment during maintenance and switching therapy, if available, at the time of conversion from MRD− to MRD+. |
| Frail patients | IMWG definition | Dose-adjusted triplet or doublets Dex-sparing regimens or quick dex held |
CELMoDs, cereblon E3 ligase modulator; dex, dexamethasone; HR, high-risk; PD, progressive disease.
t(4;14) if concomitant presence of a second unfavorable genetic abnormality or clinical feature, t(14;16), t(14;20), amplification 1q (≥4 copies), del1p, del17p in at least 55% to 60% PCs, TP53 biallelic inactivation (double-hit TP53), HR GEP signature.
>0.07% circulating PCs.
Traditionally defined: circulating PCs >20% or 2 × 109.