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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.
Myeloma almost always returns, and each return is harder to treat. Two kinds of immune therapy aimed at the BCMA protein on myeloma cells, CAR-T cells (KarMMa-3, CARTITUDE-4) and off-the-shelf bispecific antibodies (MajesTEC), now give deep remissions after other drugs fail, and a second target, GPRC5D, gives another option.
Relapse is defined by a rising M-protein or light chains, and refractory disease by progression on or within 60 days of a treatment. Choice at each relapse depends on which classes the disease has already resisted: proteasome inhibitors, immunomodulatory drugs and CD38 antibodies define triple-class exposure, and their five main members define penta-exposure. Early relapse after a lenalidomide-based first line is usually treated with a carfilzomib or pomalidomide triplet with a CD38 antibody, or with belantamab mafodotin combinations after DREAMM-7 (belantamab-bortezomib-dexamethasone versus daratumumab-bortezomib-dexamethasone, median progression-free survival 36.6 versus 13.4 months, hazard ratio 0.41, with a survival gain) and DREAMM-8 returned the antibody-drug conjugate to the market in 2025.
BCMA-directed T-cell therapies changed the outlook for later lines. Idecabtagene vicleucel was the first CAR-T approved (2021); KarMMa-3 then showed it beat standard regimens after two to four prior lines, median progression-free survival 13.3 versus 4.4 months (hazard ratio 0.49). Ciltacabtagene autoleucel produced responses in 98 percent of heavily pretreated patients in CARTITUDE-1, with a third still progression-free at five years without further treatment, and CARTITUDE-4 showed it after one to three prior lines cut progression or death by about three quarters (hazard ratio 0.26) and lengthened life (hazard ratio 0.55), moving CAR-T to second line in 2024. Bispecific antibodies give an off-the-shelf alternative: teclistamab (MajesTEC-1, response rate 63 percent, approved 2022), elranatamab (MagnetisMM-3, 61 percent) and linvoseltamab (LINKER-MM1, 70 percent, approved 2025) against BCMA, and talquetamab (MonumenTAL-1, about 73 percent, approved 2023) against GPRC5D, which works after BCMA therapy fails. MajesTEC-3 (2025) showed teclistamab with daratumumab beating standard combinations in early relapse.
| Setting | Approach | Guideline |
|---|---|---|
| First relapse, lenalidomide-refractory | Daratumumab or isatuximab with carfilzomib or pomalidomide and dexamethasone; belantamab mafodotin with bortezomib- or pomalidomide-dexamethasone (DREAMM-7, DREAMM-8); cilta-cel after one to three lines (CARTITUDE-4). | not mapped |
| Triple-class exposed, two or more prior lines | BCMA CAR-T (cilta-cel or ide-cel, KarMMa-3) where slots and fitness allow; BCMA bispecific (teclistamab, elranatamab, linvoseltamab) otherwise; teclistamab-daratumumab (MajesTEC-3). | not mapped |
| After BCMA-directed therapy | Talquetamab against GPRC5D (MonumenTAL-1); selinexor combinations; CELMoDs and trispecifics in trials. | not mapped |
| Toxicity management | Step-up dosing and tocilizumab for cytokine release syndrome, immunoglobulin replacement and antimicrobial prophylaxis on bispecifics, neurological monitoring after cilta-cel, ocular examinations on belantamab. | not mapped |