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Chapter 87 Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma 1429

High-Dose Therapy and Stem Cell Transplant progression-free survival. 155,165,176,179,188 Response assessments in WM
The European Bone Marrow Transplant Registry (EBMT) reported rely primarily on serum IgM or IgM paraprotein levels, though
the largest experience for both autologous as well as allogeneic SCT complete responses require disappearance of the IgM monoclonal
in WM. 185,186 Among 158 patients with WM receiving an autologous protein, and resolution of evidence of BM and/or extramedullary
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SCT, which included primarily relapsed or refractory patients, the disease. An important concern with the use of IgM as a surrogate
5-year progression-free and overall survival rates were 39.7% and marker of disease is that it can fluctuate independent of tumor cell
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68.5%, respectively. Nonrelapse mortality at 1 year was 3.8%. killing with some agents. By way of example, rituximab can induce
Chemorefractory disease and the number of prior lines of therapy at a flare in serum IgM levels, whereas everolimus, bortezomib, and
the time of the autologous SCT were the most important prognostic ibrutinib can suppress IgM levels independent of tumor cell killing
factors for progression-free and overall survival. In the allogeneic SCT in some patients, a phenomenon referred to as IgM discor-
experience from the EBMT, the long-term outcomes of 86 patients dance. 158,159,162,181,183,189 Moreover, with selective B cell–depleting
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with WM were reported. A total of 86 patients received an allograft agents such as rituximab and alemtuzumab, residual IgM-producing
following either myeloablative or reduced-intensity conditioning. plasma cells are spared and persist, thus potentially skewing the rela-
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The median age of patients in this series was 49 years, and 47 patients tive response and assessment to treatment. Soluble CD27 levels
had undergone three or more previous lines of therapy. Eight patients have been investigated as an alternative surrogate marker in WM,
failed prior autologous SCT. Fifty-nine patients (68.6%) had given their correlation with WM disease burden, and may remain a
chemotherapy-sensitive disease at the time of allogeneic SCT. Non- faithful marker of disease in patients experiencing a rituximab-related
relapse mortality rates at 3 years were 33% for patients receiving a IgM flare, as well as after plasmapheresis. 60,191 The use of quantitative
myeloablative transplant and 23% for those who received reduced- allele-specific PCR assays to assess serial MYD88 L265P burden in
intensity conditioning. The ORR was 75.6%. The relapse rates at 3 patients with WM is also under investigation. 36,38
years were 11% for myeloablative and 25% for reduced-intensity
conditioning recipients. Five-year progression-free and overall survival
for patients with WM who received a myeloablative allogeneic SCT Course and Prognosis
were 56% and 62%, respectively, and for patients who received
reduced intensity conditioning, the rates were 49% and 64%, respec- WM typically presents as an indolent disease. The presence of 6q
tively. The occurrence of chronic graft-versus-host disease was associ- deletions may have prognostic significance, although this is dis-
ated with improved progression-free survival and suggested the puted. 20,21 Age is an important prognostic factor (>65 years), 192–194
existence of a clinically relevant graft-versus-WM effect in this study. but it is influenced by comorbidities. Anemia that reflects both
marrow involvement and the serum level of the IgM monoclonal
Response Criteria in Waldenström protein (because of the impact of IgM on intravascular fluid reten-
tion) has emerged as a strong adverse prognostic factor with hemo-
Macroglobulinemia globin levels of <9 to 12 g/dL associated with decreased survival in
several series. 192–194 Other cytopenias also may be significant predic-
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Table 87.3 summarizes the response categories and criteria for pro- tors of survival. The precise level of cytopenias with prognostic
gressive disease in WM based on the most recent consensus recom- significance has not been determined. Some series have identified a
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9
mendations. The term overall response is used to characterize all platelet count of <100 to 150 × 10 /L and a granulocyte count of
9
responses, including minor responses. Major responses include partial, <1.5 × 10 /L as independent prognostic factors. 193,194 The number of
very good partial, and complete responses. The attainment of very cytopenias in a given patient has been proposed as a prognostic
193
good partial or complete responses is associated with improved factor. Serum albumin levels also correlate with survival in patients
TABLE Summary of Consensus Response Criteria for Waldenström Macroglobulinemia 187
87.3
Response Type Abbreviation Criteria
Complete CR Absence of serum monoclonal IgM protein by immunofixation
response Normal serum IgM level
Complete resolution of extramedullary disease (i.e., lymphadenopathy/splenomegaly if present at baseline)
Morphologically normal bone marrow aspirate and trephine biopsy
Very good partial VGPR Monoclonal IgM protein is detectable
response 90% reduction in serum IgM level from baseline or normalization of serum IgM level
Complete resolution of extramedullary disease (i.e., lymphadenopathy/splenomegaly if present at baseline)
No new signs or symptoms of active disease
Partial response PR Monoclonal IgM protein is detectable
≥50% but <90% reduction in serum IgM level from baseline
Reduction in extramedullary disease (i.e., lymphadenopathy/splenomegaly if present at baseline)
No new signs or symptoms of active disease
Minor response MR Monoclonal IgM protein is detectable
≥25% but <50% reduction in serum IgM level from baseline
No new signs or symptoms of active disease
Stable disease SD Monoclonal IgM protein is detectable
<25% reduction and <25% increase in serum IgM level from baseline
No progression in extramedullary disease (i.e., lymphadenopathy/splenomegaly)
No new signs or symptoms of active disease
Progressive PD >25% increase in serum IgM level from lowest nadir (requires confirmation) and/or progression in clinical features
disease attributable to the disease
IgM, Immunoglobulin M.