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Fit patients with newly diagnosed myeloma receive four drugs at once, then their own stem cells are collected, they are given high-dose chemotherapy, the cells are returned and they continue on maintenance. Adding the CD38 antibody daratumumab to the three-drug backbone, tested in PERSEUS and CASSIOPEIA, means most patients now reach a state where no myeloma can be detected.
Eligibility for autologous transplant rests on age, organ function and frailty rather than a fixed cut-off; most centres transplant to around 70 to 75. The sequence is three to six cycles of induction, stem cell mobilisation and collection, high-dose melphalan with autologous stem cell rescue, consolidation and then lenalidomide maintenance until progression. Two randomised trials settled the place of the transplant in the era of modern induction: IFM 2009 and DETERMINATION both showed a longer remission with early transplant after bortezomib-lenalidomide-dexamethasone (median progression-free survival 67.5 versus 46.2 months in DETERMINATION) but no survival difference, so delayed transplant at first relapse is an accepted choice.
Induction moved from triplets to quadruplets on the strength of CD38 antibodies. CASSIOPEIA (2019) added daratumumab to bortezomib-thalidomide-dexamethasone and raised stringent complete responses after consolidation from 20 to 29 percent while cutting progression or death by about half. PERSEUS (2024) added daratumumab to bortezomib-lenalidomide-dexamethasone around transplant with daratumumab-lenalidomide maintenance: progression-free survival at four years 84.3 percent versus 67.7 percent (hazard ratio 0.42), with three in four patients reaching MRD negativity at 10^-5, and daratumumab-VRd became the standard induction with regulatory approval in 2024. Isatuximab quadruplets (IsKia, GMMG-HD7) show the same pattern.
Maintenance with lenalidomide until progression lengthens life (Myeloma XI, CALGB 100104); whether to add a CD38 antibody, and whether MRD-negative patients can stop, are the questions of the MIDAS, DRAMMATIC and other MRD-adapted trials. The larger question is whether the transplant itself is still needed when quadruplets produce such deep responses, and CARTITUDE-6 is testing cilta-cel CAR-T in its place. High-risk cytogenetics (del(17p), t(4;14), t(14;16), gain or amplification of 1q) still predict early relapse and are treated with the deepest available regimens, sometimes with tandem transplant.
Roughly four in ten people with newly diagnosed myeloma are fit enough for high-dose melphalan with an autologous stem cell transplant, generally those under about 70 without major organ disease.
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-ineligible, 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
Daratumumab plus bortezomib, lenalidomide and dexamethasone (PERSEUS) for four to six cycles; isatuximab-VRd or daratumumab-VTd (CASSIOPEIA) are alternatives.
High-dose melphalan with autologous stem cell transplant, early or deferred to first relapse after stem cell collection; tandem transplant considered in high-risk disease.
Lenalidomide until progression; daratumumab added after daratumumab-based induction (PERSEUS); bortezomib-containing maintenance in high-risk disease; MRD-guided stopping in trials.
M-protein and free light chains every cycle, MRD by sequencing or flow cytometry after transplant and during maintenance, imaging for residual focal lesions.
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PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.
Quadruplet induction with a CD38 antibody became the standard for transplant-eligible patients in Europe. PERSEUS later did the same with the lenalidomide-based backbone used elsewhere.
Upfront transplant remains standard for fit patients because it lengthens the first remission, but deferring it to first relapse is a reasonable choice for some, particularly with deeper modern induction.
The stage on a myeloma report, and the label of high-risk disease that drives intensified treatment and trial choice, comes from the R-ISS; the 2022 R2-ISS adds 1q gain.
Query for this cancer: (TITLE:"Newly diagnosed multiple myeloma, transplant-eligible" OR ABSTRACT:"Newly diagnosed multiple myeloma, transplant-eligible" OR TITLE:"Transplant-eligible myeloma" OR ABSTRACT:"Transplant-eligible myeloma" OR TITLE:"TE NDMM" OR ABSTRACT:"TE NDMM" OR TITLE:"Newly diagnosed myeloma, fit for autologous transplant" OR ABSTRACT:"Newly diagnosed myeloma, fit for autologous transplant") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Newly diagnosed multiple myeloma, transplant-eligible, 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.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
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.
The leukaemia risk after chemotherapy was described in the era of mustards and etoposide, and it did not stay there. Platinum drugs carry it, PARP inhibitors raise it about two and a half times against placebo, and lenalidomide with oral melphalan raises it nearly fivefold against melphalan alone. The absolute numbers are small, but the choice of partner drug is sometimes a real decision.
See all on the product pages:BortezomibDexamethasoneLenalidomideMelphalan (including hepatic delivery system)·Printable cards in the navigator
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