Multiple myeloma: lines of therapy
10 standard-of-care settings across 6 lines and 3 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.
| Line | All comers | FRα | Risk group |
|---|---|---|---|
| Early / localised | · | · | 2 |
| Advanced, first line | 3 | · | · |
| Maintenance | 1 | · | · |
| Second line | 2 | · | · |
| Third line and beyond | · | 1 | · |
| Special situations | 1 | · | · |
Early / localised
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| Risk group | MGUS / low-risk smouldering | Observation with periodic labs; no treatment outside trials. | NCCN · Observation | 30 | |
| Risk group | High-risk smouldering myeloma | Consider daratumumab monotherapy (AQUILA) or lenalidomide (E3A06), or trial enrolment; shared decision given indolent course in many. | NCCN · Category 2A (daratumumab or lenalidomide fo… | 91 |
Advanced, first line
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Newly diagnosed | Dara-VRd ± ASCT → lenalidomide maintenance. | NCCN Guidelines: Multiple Myeloma | 32 | |
| All comers | Newly diagnosed, transplant-eligible | Dara-VRd (or Isa-VRd) induction × 4-6 → stem-cell collection → high-dose melphalan + autologous transplant → Dara-VRd consolidation → lenalidomide (± daratumumab) maintenance; MRD-guided de-escalation emerging (PERSEUS design). Tandem transplant or extended therapy for high risk. | NCCN · Category 1 (Dara-VRd)ESMO-MCBS · A | 91 | |
| All comers | Newly diagnosed, transplant-ineligible | Dara-VRd (CEPHEUS) or Isa-VRd (IMROZ) with bortezomib de-escalation after induction; Dara-Rd (MAIA) for frailer patients; continuous therapy with dose adjustment for frailty. | NCCN · Category 1 | 91 |
Maintenance
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Maintenance | Lenalidomide until progression (CALGB 100104, Myeloma XI); daratumumab added for high-risk or per PERSEUS; MRD-guided discontinuation in trials (DRAMMATIC, MASTER); iberdomide maintenance (EXCALIBER) pending. | 91 |
Second line
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Relapsed | CAR-T or bispecific; belantamab combinations; sequencing by prior exposure. | NCCN Guidelines: Multiple Myeloma | 82 | |
| All comers | First relapse (1-3 prior lines) | Cilta-cel if lenalidomide-refractory (CARTITUDE-4); teclistamab + daratumumab (MajesTEC-3, 2026); ide-cel after ≥2 lines; belantamab-Vd or -Pd (DREAMM-7/8); CD38-based triplets (Dara-Kd, Isa-Kd, Dara-Pd) by prior exposure; carfilzomib or pomalidomide combinations. | NCCN · Category 1 (cilta-cel ≥1 line; tec-dara ≥1 … | 87 |
Third line and beyond
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| FRα | Triple-class refractory (≥3-4 prior lines) | BCMA CAR-T if not yet given; bispecifics (teclistamab, elranatamab, linvoseltamab; talquetamab after BCMA exposure); belantamab; selinexor-based; CELMoDs in trials; anito-cel (PDUFA Dec 2026). | 82 |
Special situations
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Supportive care | Bisphosphonate or denosumab for bone disease; IVIG, antiviral, PJP prophylaxis and vaccination during T-cell redirection; thromboprophylaxis with IMiDs; renal protection; radiotherapy for painful lesions or cord compression. | 91 |
Sequence and caution pairings
When a BCMA drug stops working, switching to a drug against a different myeloma protein still produces responses in about two-thirds of patients.
Myeloma bispecifics and CAR-T suppress antibody production so profoundly that infections, not the cancer, became a leading cause of death in early trials.
Regimens in the library
Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.