Loading
9 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.
Most people with newly diagnosed myeloma are too old or frail for a stem cell transplant. Combining a CD38 antibody with lenalidomide and dexamethasone (MAIA) and, for the fitter, with bortezomib as well (IMROZ), now keeps the disease away for around five years in many and lengthens life.
Transplant ineligibility is decided on frailty, comorbidity and organ function using the IMWG frailty index rather than age alone, and treatment intensity is scaled to it: fit older patients receive quadruplets, frail patients doublets or attenuated triplets with dose reductions. Continuous therapy until progression is the rule, since SWOG S0777 and FIRST showed that stopping shortens remission. Supportive care carries as much weight as the anti-myeloma drugs: bone protection with zoledronic acid or denosumab, infection prophylaxis, thrombosis prophylaxis on lenalidomide and attention to neuropathy from bortezomib.
MAIA (2019) randomised 737 patients, median age 73, to daratumumab-lenalidomide-dexamethasone or lenalidomide-dexamethasone until progression: progression or death fell by 44 percent (hazard ratio 0.56), median progression-free survival later reached about five years, and the antibody lengthened overall survival (hazard ratio 0.68 at five years), making daratumumab-Rd the standard for older patients. IMROZ (2024) tested a quadruplet in fitter transplant-ineligible patients up to 80: isatuximab with bortezomib-lenalidomide-dexamethasone against VRd gave five-year progression-free survival of 63.2 percent versus 45.2 percent (hazard ratio 0.60), and CEPHEUS did the same with daratumumab-VRd, raising MRD negativity from 39.4 to 60.9 percent (progression-free survival hazard ratio 0.57). Both quadruplets are approved.
| Setting | Approach | Guideline |
|---|---|---|
| Fit, transplant-ineligible | Isatuximab or daratumumab with bortezomib, lenalidomide and dexamethasone (IMROZ, CEPHEUS), continuing the antibody and lenalidomide until progression. | not mapped |
| Intermediate fitness | Daratumumab with lenalidomide and dexamethasone until progression (MAIA). | not mapped |
| Frail | Daratumumab-Rd with reduced lenalidomide and dexamethasone, or lenalidomide-dexamethasone alone, with early dose reduction and steroid tapering. | not mapped |
| Supportive care, all patients | Bisphosphonate or denosumab bone protection, antiviral and thrombosis prophylaxis, vaccination, renal protection and early management of neuropathy. | not mapped |