Newly Diagnosed Myeloma

In standard risk patients the choice of early or deferred auto transplant is based on patient age and preference. If opting for early ASCT, then this is usually undertaken after 4 cycles of initial therapy. After auto ASCT, maintenance therapy is needed.

This approach is for transplant ineligible patients and for patents who have deferred auto transplant for later at the relapsed stage. In standard risk patients deferred auto transplant is an alternative to early transplant, but stem cells should be preferably collected early and stored. In patients not undergoing transplant (transplant ineligible or transplant deferred), initial therapy is usually done for about 6 months, followed by maintenance. Maintenance therapy consists of lenalidomide and often an anti-CD38 antibody, either daratumumab or isatuximab. Lenalidomide maintenance is supported by multiple randomized trials in which continued Lenalidomide was used as standard, and is guideline-standard; adding anti-CD38 antibody in maintenance is supported in specific contemporary regimens/trials and is evolving compared to lenalidomide alone. Maintenance Approach for standard-risk disease in patients who are transplant ineligible or transplant deferred. 1) Use lenalidomide maintenance for 2 years. 2) If daratumumab + lenalidomide maintenance is selected: - Continue lenalidomide for 2 years. - Continue daratumumab (or isatuximiab) until disease progression or unacceptable toxicity. Note: - Individualize treatment according to response, MRD status, tolerability, infection risk, cytopenias, renal function, patient preference, access, and prior anti-CD38 exposure. - Monitor CBC, renal function, thromboembolic risk, infections, rash, diarrhea, fatigue, and secondary primary malignancies. - Do not extrapolate the daratumumab schedule automatically to isatuximab-containing maintenance; follow the selected protocol and available evidence.

This node recommends early autologous stem-cell transplant as part of initial therapy in eligible patients. Randomized trials in the novel-agent era show deeper responses and longer PFS with early ASCT compared with continued therapy alone, supporting guideline inclusion of early ASCT as a standard option.