Version July 2025
DRd: daratumumab, lenalidomide, and dexamethasone; DVRd: daratumumab, bortezomib, lenalidomide, and dexamethasone; ECOG: Eastern Cooperative Oncology Group; FISH: fluorescence in situ hybridization; HCT: hematopoietic cell transplantation; IsaRd: isatuximab, lenalidomide, and dexamethasone; IsaVRd: isatuximab, bortezomib, lenalidomide, and dexamethasone; MM: multiple myeloma; MRD: measurable residual disease; NYHA: New York Heart Association; Rd: lenalidomide plus dexamethasone; VRd: bortezomib, lenalidomide, and low-dose dexamethasone.
* Risk stratification is based on results of FISH on the bone marrow for detection of t(4;14), t(14;16), t(14;20), and del17p13. FISH for 1q gain is included, if available.
¶ Eligibility for autologous HCT in MM varies across countries and institutions. In most centers in the United States, patients with one or more of the following are not considered eligible for autologous HCT in myeloma: Age >77 years, frank cirrhosis of the liver, ECOG performance status 3 or 4 unless due to bone pain, and NYHA functional status class III or IV.
Δ Single HCT is preferred for most patients. We offer double (tandem) HCT to some patients with del17p. With this approach, a second autologous HCT is performed within six months after the completion of the first.
◊ For patients with high-risk MM, we offer maintenance until progression or unacceptable toxicity with a combination of bortezomib plus lenalidomide rather than lenalidomide alone. Maintenance with lenalidomide plus carfilzomib is an acceptable alternative for patients unable to tolerate standard-dose bortezomib due to neuropathy. The combination of daratumumab plus lenalidomide is an acceptable alternative for patients who cannot tolerate bortezomib or carfilzomib.
§ The number of cycles used for an individual patient depends upon how well they tolerate the regimen and the response to treatment. If the disease continues to respond and the patient is tolerating therapy, we will offer up to 12 cycles of initial therapy.
¥ Acceptable alternatives for frail patients include VRd and DRd. If VRd is used, we offer maintenance with both lenalidomide and bortezomib. For those initially treated with DRd, we offer maintenance with both lenalidomide and daratumumab.
‡ DVRd and IsaVRd deepen responses and improve progression-free survival compared with VRd, albeit with increased toxicity and cost.
† An "early" HCT approach incorporates HCT into the initial treatment while a "delayed" HCT approach reserves HCT until first relapse. For patients with standard-risk MM, early and delayed transplant strategies have been associated with similar survival rates. The choice between early and delayed HCT is influenced by patient preference and age, response and tolerability to the initial chemotherapy regimen, insurance approval, and institutional limitations. Refer to related UpToDate content for more details.
** For patients with standard-risk MM who receive quadruplet therapy (DVRd or IsaVRd) induction, we offer maintenance with single-agent lenalidomide until progression. For patients who receive induction with the triplet VRd, maintenance with lenalidomide plus daratumumab is a reasonable alternative for those who are willing to accept a modest increase in toxicity (cytopenias, infections) with the goal of delaying progression, and for patients who remain MRD positive after 8 to 12 cycles of induction. For those initially treated with DRd, we offer maintenance with both lenalidomide and daratumumab.
