Waldenstrom's Macroglobulinemia: A SEER Database Review From 1981-2005.

Abstract Abstract 2926 Poster Board II-902 Introduction: Waldenstrom's Macroglobulinemia (WM) is a relatively rare hematopoietic neoplasm, with literature data mostly limited to small series of patients. We conducted a review of the Surveillance Epidemiology and End Results (SEER) database for WM analyzing 2969 cases from 1981-2005. Results: The incidence of reported cases of WM was stable during the studied time period at 0.3 per 100,000. The median age at diagnosis was 73 (range 23-98). There were 1661 male cases of WM and 1038 female cases (incidence ratio of 1.6:1). There were 2435 Caucasian cases and 264 non-Caucasian cases (incidence ratio of 9.2:1). Median overall survival for the entire cohort was 65 months (95% CI, 61-69). Five-year overall survival was 52% (95% CI, 50-55%). There was a significant difference in survival for individuals age <60 years versus age ≥60 years with age-adjusted 5 year overall survivals of 78% (95% CI, 44-49%) and 47% (95% CI, 44-49%), p<0.0001, respectively. Gender and race had no impact on overall survival (p=0.23 and 0.13, respectively). There was no improvement in survival over the time period analyzed. The cohort of patients diagnosed in 1981-1995 had a 5-year overall survival of 50% (95% CI, 46-54%), and those diagnosed in 1996-2005 had a 5-year overall survival of 54% (95%CI, 51-57%), p=0.18. Conclusion: This survey represents the largest cohort of WM analyzed to date. Age was shown to be the sole predictor of overall survival. Furthermore, these results underscore the little therapeutic progress we have made for this disease considering the lack of improvement in overall survival over a quarter century. Disclosures: Vij: Otsuka Pharmaceuticals: Research Funding.

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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

Journal of Clinical Oncology ◽

10.1200/jco.21.00105 ◽

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.

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International Phase III Study of Chlorambucil Versus Fludarabine As Initial Therapy for Waldenstrom's Macroglobulinemia and Related Disorders: Results in 414 Patients on Behalf of FCG CLL/ WM, GOELAMS, GELA, NCRI, ALLG

Blood ◽

10.1182/blood.v118.21.776.776 ◽

2011 ◽

Vol 118 (21) ◽

pp. 776-776 ◽

Cited By ~ 1

Author(s):

Veronique Leblond ◽

Julie Lejeune ◽

Olivier Tournilhac ◽

Pierre Morel ◽

marie Sarah Dilhuydy ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Second Malignancies ◽

Waldenström’S Macroglobulinemia ◽

Advisory Committees ◽

Free Survival ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Waldenström's Macroglobulinemia ◽

Grade Iii

Abstract Abstract 776 Background: Waldenstrom's macroglobulinemia (WM) and related-disorders (Marginal Zone Lymphoma: MZL, and non immunoglobulin IgM lymphoplasmacytic lymphoma: LPL) are rare diseases Very few randomized trials were reported in this setting. Most commonly patients with WM are initially treated with an alkylating agent, such as chlorambucil (CBL) or with a nucleoside analogue such as fludarabine (F) or 2CdA, alone or in association with monoclonal antibody. Methods: WM1 study was a prospective international randomized open-label study that included patients with previously untreated WM MZL and LPL. At registration, patients were stratified as having WM, SLVL, or LPL, and were randomized in the two arms. The aim of the study was to compare the efficacy of oral CBL at a dose of 8 mg/m2 for 10 days every 28 days to a maximum of 12 cycles with oral F at a dose of 40 mg/m2 orally for 5 days every 28 days to a maximum of 6 cycles. 418 patients were enrolled into the study from 07/01 to12/09. 414 patients were included and 405 received at least one course of chemotherapy. There were 339 WM, 37 MZL and 38 LPL with a median age of 68 years (40-89). 207 patients were randomized in the F arm and 207 patients in the CBL arm. At inclusion, the median of haemoglobin (g/l), platelets (Giga/l), albumin (g/l) and beta 2 microglobulin (mg/l) were 9.9, 218, 37.1 and 3.47 respectively. Results: In intention to treat basis, the overall response rate (CR+PR) was 47.8 % in the F arm versus 38.6% in the CBL arm (p=0.06). With a median follow-up time of 35.9 months, the median of progression free survival time (PFS) and disease free survival (DFS) were statistically longer in the F arm: PFS 36.3m vs 27.1 m ( p=0.01) and DFS 38.3m vs 19. 9m (p= 0.0006). In WM group, factors influencing negatively PFS were CBL arm, albumin< 35g/l, platelets<100 G/l and age> 70 years. Main toxicity was haematological with 17/203 (8.3%) vs 18/203 (9%) of grade III- IV thrombocytopenia and 50/203 (24.6%) vs 39/202 (19.3%) of grade III-IV anemia in F and CBL arms respectively. Overall survival rate at 5 years was 61.4% [52.9;71.3] in CBL arm and 70.3% [62.7-78.8] in F arm (p=0.04) (Fig 1). Cumulative Incidence of second malignancies (solid tumors and haematological malignancies except Richter syndrome (RS)) was statistically higher in the chlorambucil arm (25 versus 8, p= 0.004) (Fig 2). The number of RS was 8 in F arm and 9 in CBL arm. Conclusion: F by oral route is a safe and effective ambulatory treatment in WM and close related disorders patients, even in the elderly and more effective than CBL with a duration of response over 3 years. An unexpected finding was a statistically higher number of second malignancies in the C arm and we cannot rule out an oncogenic role of CBL in this setting. Of note, we stress that it is the first time that a front- line treatment has a significant impact on overall survival in WM patients. Disclosures: Leblond: mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tournilhac:Amgen: Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees.

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