Immunoglobulin M ‘Flare’ after rituximab-associated acute tubular necrosis in Waldenström’s macroglobulinemia

2009 ◽  
Vol 89 (2) ◽  
pp. 218-222 ◽  
Author(s):  
Hassane Izzedine ◽  
Edward Bourry ◽  
Lucile Amrouche ◽  
Isabelle Brocheriou ◽  
Madalina Uzunov ◽  
...  
Keyword(s):  
Acute Tubular Necrosis ◽  
Immunoglobulin M ◽  
Waldenström’S Macroglobulinemia ◽  
Tubular Necrosis ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenström's macroglobulinemia.

1993 ◽  
Vol 11 (5) ◽  
pp. 914-920 ◽  
Author(s):  
M A Gertz ◽  
R A Kyle ◽  
P Noel
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Subcutaneous Fat ◽  
Immunoglobulin M ◽  
Entire Group ◽  
Waldenström’S Macroglobulinemia ◽  
Cardiac Amyloid ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

PURPOSE To determine the natural history of amyloidosis associated with Waldenström's macroglobulinemia and immunoglobulin M (IgM) monoclonal gammopathy. PATIENTS AND METHODS From January 1968 to September 1990, 50 patients with a serum IgM monoclonal protein and biopsy-proven amyloidosis were evaluated at the Mayo Clinic. There were 32 men and 18 women (age range, 43 to 93 years). RESULTS Percentages of patients presenting with cardiac, renal, hepatic, and pulmonary amyloid were 44%, 32%, 14%, and 10%, respectively. Forty-two percent of the patients had an M protein value greater than 1.5 g/dL, and 12% had an M component greater than 3 g/dL. Subcutaneous fat, rectum, and bone marrow showed amyloid in 84%, 72%, and 50%, respectively, providing a simple technique for diagnosing amyloidosis. The bone marrow biopsy was consistent with Waldenström's macroglobulinemia in 10, a plasma-cell proliferative disorder in 10, and lymphoma or a lymphoproliferative disorder in 11; results were normal, nondiagnostic, or hypercellular in 17. Forty-three of 50 patients died. The median survival of the entire group was 24.6 months. Fifty-three percent of deaths were due to cardiac amyloid, 12% to respiratory failure, 7% to macroglobulinemia, 7% to liver failure, and 7% to kidney failure. CONCLUSION The presence of amyloid cardiomyopathy and an increased creatinine concentration at diagnosis had an adverse impact on survival. Of the 22 patients who presented with cardiomyopathy, the median survival was 11.1 months, with only two surviving longer than 5 years. The median survival of the 28 patients without cardiomyopathy at diagnosis was 27 months, with eight 5-year survivors (P = .013). All eight amyloid deposits studied stained for Ig light chain, indicating that this amyloidosis is of the primary (AL) type.

scholarly journals Immunoglobulin M Monoclonal Gammopathies of Undetermined Significance and Indolent Waldenström's Macroglobulinemia Recognize the Same Determinants of Evolution Into Symptomatic Lymphoid Disorders: Proposal for a Common Prognostic Scoring System

2005 ◽  
Vol 23 (21) ◽  
pp. 4662-4668 ◽  
Author(s):  
Luca Baldini ◽  
Maria Goldaniga ◽  
Andrea Guffanti ◽  
Chiara Broglia ◽  
Sergio Cortelazzo ◽  
...  
Keyword(s):  
Scoring System ◽  
Immunoglobulin M ◽  
Neoplastic Progression ◽  
Waldenström’S Macroglobulinemia ◽  
Female Ratio ◽  
Monoclonal Gammopathies ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia ◽  
Undetermined Significance

Purpose To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. Patients and Methods We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. Results After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). Conclusion MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.

scholarly journals Combining Ixazomib With Subcutaneous Rituximab and Dexamethasone in Relapsed or Refractory Waldenström's Macroglobulinemia: Final Analysis of the Phase I/II HOVON124/ECWM-R2 Study

2021 ◽  
pp. JCO.21.00105
Author(s):  
Marie José Kersten ◽  
Karima Amaador ◽  
Monique C. Minnema ◽  
Josephine M. I. Vos ◽  
Kazem Nasserinejad ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Progression Free Survival ◽  
Immunoglobulin M ◽  
Waldenström’S Macroglobulinemia ◽  
Minor Response ◽  
Free Survival ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

PURPOSE Proteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM. METHODS We conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for phase II was overall response rate (ORR [≥ minimal response]) after induction. RESULTS A total of 59 patients were enrolled (median age, 69 years; range, 46-91 years). Median number of prior treatments was 2 (range 1-7); 70% had an intermediate or high WM-IPSS (International Prognostic Scoring System for WM) score. After eight cycles, ORR was 71% (42 out of 59) (14% very good partial response [PR], 37% PR, and 20% minor response). Depth of response improved until month 12 (best ORR 85% [50 out of 59]: 15% very good PR, 46% PR, and 24% minor response). Median duration of response was 36 months. The average hematocrit level increased significantly (0.33-0.38 L/L) after induction ( P < .001). After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decreased significantly (median 3,700-2,700 mg/dL, P < .0001). Median time to first response was 4 months. Median progression-free survival and overall survival were not reached. After median follow-up of 24 months (range, 7.4-54.3 months), progression-free survival and overall survival were 56% and 88%, respectively. Toxicity included mostly grade 2 or 3 cytopenias, grade 1 or 2 neurotoxicity, and grade 2 or 3 infections. No infusion-related reactions or immunoglobulin M flare occurred with use of subcutaneous rituximab. Quality of life improved significantly after induction. In total, 48 patients (81%) completed at least six cycles of IRD. CONCLUSION Combination of IRD shows promising efficacy with manageable toxicity in patients with relapsed or refractory WM.

Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.

1998 ◽  
Vol 16 (6) ◽  
pp. 2060-2064 ◽  
Author(s):  
V Leblond ◽  
T Ben-Othman ◽  
E Deconinck ◽  
A L Taksin ◽  
J L Harousseau ◽  
...  
Keyword(s):  
Alkylating Agents ◽  
Nucleoside Analogs ◽  
Median Number ◽  
Immunoglobulin M ◽  
Waldenström’S Macroglobulinemia ◽  
Secondary Resistance ◽  
Failure Group ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

PURPOSE There is no consensus on the treatment of patients with Waldenström's macroglobulinemia (WM) who develop primary or secondary resistance to frontline therapies. We report our experience on the activity and toxicity of fludarabine in 71 patients with WM resistant to prior chemotherapy regimens. PATIENTS AND METHODS From January 1991 to June 1995, 71 patients were included in this retrospective study. The median age, median time from diagnosis to treatment, median immunoglobulin M (IgM) level, and median number of previous treatments were 68 years (range, 42 to 81), 5.9 years (range, 0.6 to 20), 35 g/L (range, 5 to 126), and two (range, one to four), respectively. RESULTS Seventy-one patients received a median of six courses of fludarabine. Twenty-one (30%) responded with a partial response and 50 (70%) were considered as treatment failures. Forty-six patients died: 10 in the responder group and 36 in the failure group. Twenty-five patients were alive with a median follow-up time of 34 months. The overall median survival time of all treated patients was 23 months. The time to treatment failure was 32 months. The only factor that favorably influenced the response to fludarabine was a longer interval between the first treatment and the start of fludarabine. Pretreatment factors associated with shorter survival in the entire population were hemoglobin level less than 95 g/L (P = .02) and platelet count less than 75 x 10(9)/L (P = .02). CONCLUSION The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.

Bortezomib Is Active in Patients With Untreated or Relapsed Waldenström's Macroglobulinemia: A Phase II Study of the National Cancer Institute of Canada Clinical Trials Group

2007 ◽  
Vol 25 (12) ◽  
pp. 1570-1575 ◽  
Author(s):  
Christine I. Chen ◽  
C. Tom Kouroukis ◽  
Darrell White ◽  
Michael Voralia ◽  
Edward Stadtmauer ◽  
...  
Keyword(s):  
Single Agent ◽  
Complete Response ◽  
Immunoglobulin M ◽  
Waldenström’S Macroglobulinemia ◽  
Total Response Rate ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Grade 3 ◽  
Waldenström's Macroglobulinemia

PurposeTo evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM).Patients and MethodsSymptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements.ResultsTwenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty-one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy.ConclusionBortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted.

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