Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines

Abstract

Multiple myeloma is a malignant plasma cell neoplasm that affects more than 20,000 people each year and is the second most common hematologic malignancy. It is part of a spectrum of monoclonal plasma cell disorders, many of which do not require active therapy. During the past decade, considerable progress has been made in our understanding of the disease process and factors that influence outcome, along with development of new drugs that are highly effective in controlling the disease and prolonging survival without compromising quality of life. Identification of well-defined and reproducible prognostic factors and introduction of new therapies with unique modes of action and impact on disease outcome have for the first time opened up the opportunity to develop risk-adapted strategies for managing this disease. Although these risk-adapted strategies have not been prospectively validated, enough evidence can be gathered from existing randomized trials, subgroup analyses, and retrospective studies to develop a working framework. This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence.

FIGURE 1.

Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART). FISH = fluorescence in situ hybridization; MM = multiple myeloma; PCLI = plasma cell labeling index. *Patients with t(4;14), β₂-microglobulin <4 mg/L, and hemoglobin ≥10 g/dL may have intermediate-risk disease.

FIGURE 2.

Treatment approach in patients eligible for autologous stem cell transplant. CR = complete response; iMiD = immunomodulatory drug; Rd = lenalidomide, dexamethasone; VGPR = very good partial response. *If age >65 y or ≥4 cycles of Rd, consider chemotherapy plus granulocyte—colony-stimulating factor mobilization or plerixafor. †Continuing Rd is an option for patients responding well to induction therapy with low toxicities; dexamethasone is usually discontinued after first year.

FIGURE 3.

Incremental response to stem cell transplant after induction therapy. CTD = cyclophosphamide, thalidomide, dexamethasone; Dex = dexamethasone; PAD = bortezomib, Adriamycin, dexamethasone; TAD = thalidomide, Adriamycin, dexamethasone; Thal = thalidomide; VAD = vincristine, Adriamycin, dexamethasone (dex); VD = bortezomib, dexamethasone; VGPR = very good partial response; VTD = bortezomib, thalidomide, dexamethasone.

FIGURE 4.

Treatment approach in patients ineligible for autologous stem cell transplant. MP = melphalan-prednisone; Rd = lenalidomide, dexamethasone. *Bortezomib-containing regimens preferred for patients with renal failure or if rapid response is needed. †In patients in whom administration of thalidomide or bortezomib is of concern, consider MP or Rd. ‡Continuing Rd is an option for patients responding well to induction therapy with low toxicities; dexamethasone is usually discontinued after the first year.