10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Multiple myeloma is a plasma-cell cancer with more new drug classes than any other: proteasome inhibitors, IMiDs, CD38 antibodies, BCMA CAR-T, bispecifics, and an ADC.
Multiple myeloma is a cancer of antibody-producing plasma cells in the bone marrow, causing anaemia, bone destruction, kidney failure and infections. It is preceded by MGUS and smouldering myeloma, which are common (MGUS in ~3% of people over 50) and mostly harmless; whether to treat high-risk smouldering disease (AQUILA, daratumumab) is a live debate, and Iceland is screening its whole adult population (iStopMM). Staging (R-ISS/R2-ISS) and cytogenetics (del17p, t(4;14), 1q gain) drive prognosis; MRD negativity at one in a million marrow cells has become both the best prognostic marker and, since 2024, an accepted regulatory endpoint.
No cancer has gained more drug classes: proteasome inhibitors (bortezomib 2003, carfilzomib), immunomodulatory cereblon modulators (thalidomide, lenalidomide, pomalidomide; next-generation CELMoDs iberdomide and mezigdomide), CD38 antibodies (daratumumab, isatuximab), BCMA-directed CAR-T (ide-cel, cilta-cel; anito-cel decision December 2026), BCMA and GPRC5D bispecific T-cell engagers (teclistamab, elranatamab, linvoseltamab, talquetamab), a BCMA ADC (belantamab, withdrawn 2022 and re-approved 2025), plus XPO1 and BCL-2 inhibitors for subsets. Newly diagnosed patients receive a quadruplet (Dara-VRd or Isa-VRd) whether or not they proceed to autologous transplant (PERSEUS, CEPHEUS, IMROZ), then lenalidomide maintenance; median survival in fit patients now exceeds ten years. At relapse, cilta-cel (CARTITUDE-4, OS HR 0.55) and teclistamab plus daratumumab (MajesTEC-3, approved March 2026) are second-line options, with sequencing by prior antigen exposure.
| Setting | Approach | Guideline |
|---|---|---|
| Newly diagnosed | Dara-VRd ± ASCT → lenalidomide maintenance. | not mapped |
| Relapsed | CAR-T or bispecific; belantamab combinations; sequencing by prior exposure. | not mapped |
| MGUS / low-risk smouldering | Observation with periodic labs; no treatment outside trials. | NCCN Observation |
| 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 for high-risk SMM) |
| 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 |
| 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 |
| 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. | not mapped |
| 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 line) |