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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.
The frail remain under-served: they were largely excluded from these trials, tolerate bortezomib poorly, and gain less from a fourth drug. The BENEFIT trial suggested that weekly bortezomib added to isatuximab-Rd improves MRD negativity in this group, and dose-attenuated regimens, fixed-duration therapy, and bispecific antibodies in the front line (MajesTEC-7, CEPHEUS-type designs) are the current trials.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
More than half of people diagnosed with myeloma, typically over 70 or with frailty or organ disease, are not candidates for high-dose chemotherapy; their outlook has improved more than any other group's in the past decade.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Isatuximab or daratumumab with bortezomib, lenalidomide and dexamethasone (IMROZ, CEPHEUS), continuing the antibody and lenalidomide until progression.
Daratumumab with lenalidomide and dexamethasone until progression (MAIA).
Daratumumab-Rd with reduced lenalidomide and dexamethasone, or lenalidomide-dexamethasone alone, with early dose reduction and steroid tapering.
Bisphosphonate or denosumab bone protection, antiviral and thrombosis prophylaxis, vaccination, renal protection and early management of neuropathy.
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CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Query for this cancer: (TITLE:"Newly diagnosed multiple myeloma, transplant-ineligible" OR ABSTRACT:"Newly diagnosed multiple myeloma, transplant-ineligible" OR TITLE:"Transplant-ineligible myeloma" OR ABSTRACT:"Transplant-ineligible myeloma" OR TITLE:"TI NDMM" OR ABSTRACT:"TI NDMM" OR TITLE:"Myeloma in older or frail patients" OR ABSTRACT:"Myeloma in older or frail patients" OR TITLE:"Newly diagnosed myeloma not for transplant" OR ABSTRACT:"Newly diagnosed myeloma not for transplant") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Newly diagnosed multiple myeloma, transplant-ineligible, not a curated reading list.
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A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
Venous and arterial thromboembolism risk rises markedly with lenalidomide plus dexamethasone (and further with erythropoietin or oestrogens).. Thromboprophylaxis (aspirin, LMWH or a DOAC by risk) is standard.
Dose by creatinine clearance: 10 mg daily for CrCl 30-60, 15 mg every other day below 30, 5 mg daily on dialysis.
Start at 0.7 mg/m² in moderate or severe impairment.
When engineered T cells or a bispecific antibody switch on, the immune system can overshoot. The first sign is a fever, and the treatment is a drug that blocks the main signal, given early. A smaller number of people become confused or drowsy, which is graded and treated separately.
Several lymphoma treatments knock out the part of the immune system that keeps a particular lung infection, Pneumocystis, at bay. A low-dose antibiotic three times a week prevents it, and a separate tablet prevents shingles.
See all on the product pages:BortezomibDexamethasoneLenalidomide·Printable cards in the navigator
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