Table 3.

Mayo Stratification of Risk-Adapted Therapy (mSMART): Comparison and Contrast With Other Published Guidelines

Categories	mSMART 2016	National Comprehensive Cancer Network Version 2.2016	Eighth International Workshop for WM	British Society of Haematology 2014	European Society of Medical Oncology/Japanese Society of Medical Oncology 2013
WM Definition: IgM gammopathy positive	≥10% BMLP infiltration	Any degree of BMLP infiltration	Any degree of BMLP infiltration	Any degree of BMLP infiltration	Any degree of BMLP infiltration
MYD88 mutational status assessment	With AS-PCR in (1) Suspected lymphoplasmacytic lymphoma cases that are histopathologically challenging to diagnose (2) In potential candidates for ibrutinib salvage therapy	Essential in all cases; Sanger sequencing if AS-PCR negative for MYD88 L265P	Essential in all cases; methodology based on institutional preference	Not specified	Not specified
Choice of primary therapy	Risk-adapted approach: (1) rituximab monotherapy in unique scenarios (2) BR (3) DRCa	Lists 15 regimens categorized by their potential for stem cell toxic effects	6 Regimens: (1) ibrutinib (2) BR (3) DRC (4) bortezomib-based (5) carfilzomib-based (6) rituximab monotherapyb	6 Regimens: (1) DRC (2) BR (3) FR (4) FCR (5) Clad-R (6) chlorambucil in frail patients	Medically fit: rituximab-based chemotherapy (DRC, RCHOP, BR, R-bortezomib with or without dexamethasone); medically unfit: rituximab monotherapy
Rituximab maintenance therapy	Not recommended	Considered in patients responding to rituximab-based induction	Not recommended	Not recommended	Not recommended outside clinical trials
Optimal timing of stem cell harvest	Preferably first remission in potentially ASCT-eligible patients younger than 70 y	Sometime prior to administration of stem cell toxic therapies	Optimal timing not fully specified, but prior to administration of fludarabine	Not specified	Not specified
ASCT	Strong consideration for chemosensitive, transplant-eligible patients in first relapse taking into account the patient’s preference	An option for salvage therapy (not specified whether this approach should be undertaken early or late in the disease course)	Conflicting statements; table indicates ideal in high-risk, early relapses, those who have received <3 lines of therapies or have chemosensitive WM. Text suggests considering in multiply relapsed, young patients, or in primary refractory disease	In younger fitter patients with aggressive disease (short progression-free survival or transformation) in the setting of chemosensitive disease and at least a partial response to reinduction	As salvage therapy in transplant-eligible patients with aggressive disease
Retreatment with prior therapy	TTNT of ≥36 mo from the prior therapy	Remission duration of ≥12 mo from previous therapy	Response duration of at least 24 moc	In patients with “durable response” to initial therapy	Not typically recommended
Other salvage therapeutic options	Ibrutinib or BDR; Multiply relapsed/refractory:fludarabine-based or everolimus	19 Approaches listed, including alemtuzumab, everolimus, or rituximab monotherapy, and in select patients autologous or allogeneic transplantd	(1) Ibrutinib (2) fludarabine-based (3) everolimus (4) immunomodulatory drugsd	(1) DRC (2) BR (3) FR (4) FCR (5) Clad-R (6) bortezomib based (7) alemtuzumab in refractory WM (8) ASCT or allogeneic SCT in young patients with a short first remission (<2 y)	An alternative rituximab-based chemotherapeutic agent (class should be different from that used previously; classes include alkylators, nucleoside analogs, or bortezomib based)

Abbreviations: ASCT, autologous stem cell transplantation; AS-PCR, allele-specific polymerase chain reaction; BMLP, bone marrow lymphoplasmacytic; BR, bendamustine rituximab; Clad-R, cladribine rituximab; DRC, dexamethasone-rituximab-cyclophosphamide; FCR, fludarabine-cyclophosphamide-rituximab; FR, fludarabine-rituximab; RCHOP, rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisone; TTNT, time to next therapy; WM, Waldenström macroglobulinemia.

^aAn alternative for nonbulky (absence of extensive lymphadenopathy/extramedullary) disease.

^bIn frail patients or those with IgM-mediated immunologic disorders.

^cRetreatment with ibrutinib should be avoided.

^dIn the context of clinical trials.