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1796 Part XI: Malignant Lymphoid Diseases Chapter 109: Macroglobulinemia 1797

discontinuation of everolimus led to rapid increases in serum IgM lev- RESPONSE CRITERIA IN WALDENSTRÖM
els, and symptomatic hyperviscosity. Grade 2 or higher hematologic
and nonhematologic toxicities in this study that were related to everoli- MACROGLOBULINEMIA
mus were predominately hematologic, including anemia (40 percent),
thrombocytopenia (12 percent), and neutropenia (18 percent). Non- Table 109–3 summarizes the response categories and criteria for pro-
hematologic toxicities included oral ulcerations (27 percent), which gressive disease in WM based on the most recent consensus recommen-
187
improved with oral dexamethasone swish and spit solution, and pneu- dations. The term overall response is used to characterize all responses,
monitis (15 percent), which led to treatment discontinuation. including minor responses. Major responses only include partial, very
good partial, and complete responses. The attainment of very good partial
Maintenance Therapy or complete responses is associated with improved progression-free sur-
155,165,176,179,188
A large retrospective study examined the categorical responses out- vival. Response assessments in WM rely primarily on serum
come of rituximab-naïve patients who were either observed or received IgM or IgM paraprotein levels, although complete responses require dis-
183
maintenance rituximabwere . Categorical responses improved after appearance of the IgM monoclonal protein, and resolution of marrow and/
187
induction therapy in 42 percent of patients who received maintenance or extramedullary WM disease. An important concern with the use of
rituximab versus 10 percent in patients on observation. Additionally, IgM as a surrogate marker of disease is that it can fluctuate, independent
both progression-free survival (56.3 vs. 28.6 months) and overall sur-
vival (>120 vs. 116 months) were longer in patients who received main-
tenance rituximab. Improved progression-free survival was evident TABLE 109–3. Summary of Consensus Response Criteria
despite previous treatment status or induction with rituximab, either for Waldenstrom’s Macroglobulinemia 187
alone or in combination therapy. Best serum IgM response was also Complete CR Absence of serum monoclonal IgM protein
lower and hematocrit higher in those patients who received mainte- Response by immunofixation.
nance rituximab. Among patients who received maintenance rituximab Normal serum IgM level.
therapy, an increased number of infectious events, predominantly grade Complete resolution of extramedullary dis-
1 or 2 sinusitis and bronchitis were observed, along with lower serum ease, i.e., lymphadenopathy/splenomegaly
IgA and IgG levels. A prospective study examining the role of mainte- if present at baseline.
nance rituximab was also initiated by the German STiL group. In this Morphologically normal marrow aspirate
184
study, patients received up to six cycles of bendamustine and rituximab, and trephine biopsy.
and responders randomized to either observation or maintenance ritux-
imab every 2 months for 2 years. Enrollment for this study is complete Very Good VGPR Monoclonal IgM protein is detectable.
and response outcome for maintenance rituximab therapy is awaited. Partial 90% reduction in serum IgM level from
Response baseline, or normalization of serum IgM
level.
HIGH-DOSE THERAPY AND STEM CELL Complete resolution of extramedullary dis-
TRANSPLANTATION ease, i.e., lymphadenopathy/splenomegaly
if present at baseline.
The European Bone Marrow Transplant Registry reported the largest No new signs or symptoms of active disease.
experience for both autologous as well as allogeneic stem cell transplan-
tation (SCT) in WM. 185,186 Among 158 WM patients receiving an autol- Partial PR Monoclonal IgM protein is detectable.
ogous SCT, which included primarily relapsed or refractory patients, Response ≥50% but <90% reduction in serum IgM
the 5-year progression-free and overall survival rate was 39.7 percent level from baseline.
185
and 68.5 percent, respectively. Nonrelapse mortality at 1 year was Reduction in extramedullary disease, i.e.,
3.8 percent. Chemorefractory disease, and the number of prior lines of lymphadenopathy/splenomegaly if present
therapy at time of the autologous SCT were the most important prog- at baseline.
nostic factor for progression-free and overall survival. In the alloge- No new signs or symptoms of active disease.
neic SCT experience from the European Bone Marrow Transplant, the Minor MR Monoclonal IgM protein is detectable.
long-term outcome of 86 WM patients was reported. A total of 86 Response
186
patients received allograft by either myeloablative or reduced-intensity ≥25% but <50% reduction in serum IgM
conditioning. The median age of patients in this series was 49 years, and level from baseline.
47 patients had three or more previous lines of therapy. Eight patients No new signs or symptoms of active disease.
failed prior autologous SCT. Fifty-nine patients (68.6 percent) had che- Stable SD Monoclonal IgM protein is detectable.
motherapy-sensitive disease at the time of allogeneic SCT. Nonrelapse Disease <25% reduction and <25% increase in
mortality at 3 years was 33 percent for patients receiving a myeloabla- serum IgM level from baseline.
tive transplant, and 23 percent for those who received reduced-intensity No progression in extramedullary disease,
conditioning. The overall response rate was 75.6 percent. The relapse i.e., lymphadenopathy/splenomegaly.
rates at 3 years were 11 percent for myeloablative, and 25 percent for No new signs or symptoms of active disease.
reduced-intensity conditioning recipients. Five-year progression-free
and overall survival for WM patients who received a myeloablative Progressive PD >25% increase in serum IgM level from
allogeneic SCT were 56 percent and 62 percent, respectively, and for Disease lowest nadir (requires confirmation) and/or
patients who received reduced intensity conditioning were 49 percent progression in clinical features attributable
the disease.
and 64 percent, respectively. The occurrence of chronic graft-versus-
host disease was associated with improved progression-free survival, Reproduced with permission from Owen RG, Kyle RA, Stone MJ,
and suggested the existence of a clinically relevant graft-versus-WM et al: Response Assessment in Waldenström macroglobulinemia. Br J
effect in this study. Haematol 160(2):171–176, 2013.

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