Characteristics and outcome of patients with MYD88 wild-type Waldenström Macroglobulinemia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8550-8550
Author(s):  
Saurabh Zanwar ◽  
Jithma P. Abeykoon ◽  
Stephen M. Ansell ◽  
Jonas Paludo ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
High Risk ◽  
High Risk Group ◽  
Small Subset ◽  
Continuous Variables ◽  
Recurrent Point ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Histological Transformation ◽  
Btk Inhibitor ◽  
Active Disease

8550 Background: Waldenström Macroglobulinemia (WM) is a rare lymphoplasmacytic malignancy characterized by the presence of a recurrent point mutation in the MYD88 gene (MYD88L265P) in 80-95% of cases. Patients with MYD88WT genotype comprise a small subset that responds poorly to ibrutinib and other Bruton tyrosine kinase inhibitors. We examined the characteristics and outcome of WM patients with MYD88WT genotype predominantly treated with non-BTK inhibitor based therapies. Methods: Patients with a diagnosis of WM seen at Mayo Clinic, Rochester, between 1996 and 2018 were included. Their characteristics and outcomes were assessed from the time of active disease. Marrow MYD88 genotyping was assessed with an allele specific PCR assay (analytic sensitivity 1%). Categorical and continuous variables were compared using Chi square and Wilcoxon tests, respectively. Time-to-event analyses were performed using Kaplan Meier test. Results: Of 986 patients with active WM, MYD88 genotype data were available in 331 (34 %) patients; 72 (22%) and 260 (78%) patients harbored MYD88WT and MYD88L265P genotypes, respectively. The median follow-up was 5.8 years (95% CI: 5.0-6.5 years) from active WM; 6 years MYD88WT vs 5.4 years for MYD88L265P cohort. Median age was 63 years and 66 years in the MYD88WT and MYD88L265P cohorts, respectively (p = 0.07) with 46% and 53% patients being ≥65 years of age, respectively (p = 0.36). Pre-treatment marrow lymphoplasmacytic (LPL) infiltrate (median 40% for MYD88WT vs 60% for MYD88L265P; p = 0.001) and beta-2 microglobulin (median 3 µg/mL for MYD88WT vs 3.9 µg/mL for MYD88L265P; p = 0.02) were lower in the MYD88WT compared to the MYD88L265P cohort; other laboratory parameters at active disease were comparable. Per IPSSWM prognostic criteria, MYD88WT had fewer patients in the high risk group (18% for MYD88WT vs 42% MYD88L265P; p = 0.03). Patients with MYD88WT had higher likelihood of histological transformation [18% for MYD88WT vs 4% for MYD88L265P; odds ratio 5.8 (95% CI: 2.5-13.5; p < 0.0001)]. Among patients with treatment data available, only 35 (11%) patients received ibrutinib. The 5-year overall survival (OS) from active disease was comparable (85% in MYD88WT vs 82% in MYD88L265P cohort; p = 0.7). Conclusions: MYD88WT genotype in WM is associated with lower marrow LPL infiltration, lower likelihood of high-risk IPSSWM categorization and a higher likelihood of histological transformation in comparison to MYD88L265P mutant subpopulation. MYD88 genotype does not affect the OS from active disease in predominantly non-BTK inhibitor treated patients.

scholarly journals Genomic Landscape of Waldenström Macroglobulinemia and Its Impact on Treatment Strategies

2020 ◽  
Vol 38 (11) ◽  
pp. 1198-1208 ◽  
Author(s):  
Steven P. Treon ◽  
Lian Xu ◽  
Maria Luisa Guerrera ◽  
Cristina Jimenez ◽  
Zachary R. Hunter ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
B Cell Lymphoma ◽  
Mutation Status ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Genomic Landscape ◽  
Rational Drug ◽  
Increased Risk ◽  
Impact On Treatment ◽  
Btk Inhibitor

Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM), including MYD88 (95%-97%), CXCR4 (30%-40%), ARID1A (17%), and CD79B (8%-15%). Deletions involving chromosome 6q are common in patients with mutated MYD88 and include genes that modulate NFKB, BCL2, Bruton tyrosine kinase (BTK), and apoptosis. Patients with wild-type MYD88 WM show an increased risk of transformation and death and exhibit many mutations found in diffuse large B-cell lymphoma. The discovery of MYD88 and CXCR4 mutations in WM has facilitated rational drug development, including the development of BTK and CXCR4 inhibitors. Responses to many agents commonly used to treat WM, including the BTK inhibitor ibrutinib, are affected by MYD88 and/or CXCR4 mutation status. The mutation status of both MYD88 and CXCR4 can be used for a precision-guided treatment approach to WM.

scholarly journals Progression Risk-Based Classification of Asymptomatic Waldenström Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 150-150
Author(s):  
Mark Bustoros ◽  
Romanos Sklavenitis-Pistofidis ◽  
Chia-jen Liu ◽  
Efstathios Kastritis ◽  
Geoffrey Fell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Proportional Hazards ◽  
Risk Group ◽  
Advisory Committees ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Risk Of Progression

Abstract Background. Waldenström macroglobulinemia (WM) is a low-grade non-Hodgkin's lymphoplasmacytic lymphoma associated with overproduction of monoclonal IgM protein. It is preceded by an asymptomatic stage, called Smoldering Waldenström Macroglobulinemia (SWM), associated with a high risk of progression to overt disease. Current understanding of progression risk in SWM is based on a few small studies, and it is still unclear how to distinguish the asymptomatic patients who will progress from those who will not. Patients and Methods. We obtained clinical data of all WM patients who had been diagnosed and followed up at Dana-Farber Cancer Institute from 1982 to the end of 2014. Only patients with asymptomatic disease at the time of diagnosis were included in this study to identify risk factors for disease progression. Patients who received chemotherapy for a second cancer, before or after asymptomatic WM diagnosis (n =24), were excluded as chemotherapy might have affected the natural course of disease. Patients who progressed to or were diagnosed later with other types of B-cell lymphoproliferative disorders or Amyloidosis (n =71) and patients with myeloproliferative disorders or thalassemia (n = 4) were all excluded from our cohort. Furthermore, we excluded patients with no morphologic evidence of lymphoplasmacytic infiltration in the bone marrow biopsy (n =37), those without a bone marrow biopsy done at time of diagnosis (n =21), and those who were treated for peripheral neuropathy alone (n =13). Progression was defined based on the Consensus Panel recommendations of the Second International Workshop on WM. Survival analysis was performed using the Kaplan-Meier method and differences between the curves were tested by log-rank test. Effects of potential risk factors on progression rates was examined using Cox proportional-hazards models, with hazard ratios (HRs) and associated 95% confidence intervals (CIs). Results. A total of 439 patients were included in the study. During the 35-year study period and a median follow up of 7.8 years, 317 patients (72.2%) progressed to symptomatic WM. The median time to progression was 3.9 (95% CI 3.2-4.6) years. In the multivariate analysis, IgM ≥ 4,500 mg/dL (adjusted HR 4.65; 95% CI 2.52-8.58; p < 0.001), BM lymphoplasmacytic infiltration ≥ 70% (adjusted HR 2.56; 95% CI 1.69-3.87; p < 0.001), β2-microglobulin ≥ 4.0 mg/dL (adjusted HR 2.31; 95% CI 1.19-4.49; p = 0.014), and albumin < 3.5 g/dL (adjusted HR 2.78; 95% CI 1.52-5.09; p = 0.001) were all identified as independent predictors of disease progression, suggesting those thresholds could be clinically useful for determining high-risk patients. On the other hand, given the continuous nature of these variables, we built a proportional hazards model based on four variables (Bone marrow infiltration percentage, serum IgM, albumin, β2-microglobulin). The model divided the cohort into 3 distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.9 years (95% CI 1.64-2.13), an intermediate-risk group with median TTP of 4.6 years (95% CI 4.31-5.15), and a low-risk group with a median TTP of 8.1 years (95% CI 7.33-8.13)(See Figure). To enhance its clinical applicability, we made the model available as user interface through a webpage and mobile application, where clinicians can enter an individual SWM patient's lab values and get information regarding their risk group and estimated individual risk of progression to symptomatic WM. Conclusion. We have assembled the largest cohort of SWM patients to date, which allowed us to identify four independent predictors of progression to overt disease: BM infiltration ≥ 70%, IgM ≥ 4,500 mg/dL, b2m ≥ 4.0 mg/dL and albumin < 3.5 g/dL. Using those variables in a proportional hazards model, we developed a robust, flexible classification system based on risk of progression to symptomatic WM. This system stratifies SWM patients into low-, intermediate- and high-risk groups and thus has the potential to inform patient monitoring and care. Most importantly, it can help identify high-risk patients who might benefit from early intervention in this rare malignancy. Figure 1. Figure 1. Disclosures Bustoros: Dava Oncology: Honoraria. Kastritis:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Treon:Johnson & Johnson: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; BMS: Research Funding; Pharmacyclics: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding. Castillo:Genentech: Consultancy; Millennium: Research Funding; Abbvie: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Dimopoulos:Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria. Ghobrial:BMS: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy.

scholarly journals A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study

Blood ◽  
2020 ◽  
Vol 136 (18) ◽  
pp. 2038-2050 ◽  
Author(s):  
Constantine S. Tam ◽  
Stephen Opat ◽  
Shirley D'Sa ◽  
Wojciech Jurczak ◽  
Hui-Peng Lee ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Phase 3 ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Major Response ◽  
Significant Difference ◽  
Duration Of Response ◽  
Btk Inhibitor ◽  
Grade 3

Abstract Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.

scholarly journals Pre-exposure prophylaxis use among men who have sex with men who have experienced problematic chemsex

2020 ◽  
Vol 31 (5) ◽  
pp. 474-480
Author(s):  
Steven Maxwell ◽  
Mitzy Gafos ◽  
Monty Moncrieff ◽  
Maryam Shahmanesh ◽  
Oliver Stirrup
Keyword(s):  
High Risk ◽  
High Risk Group ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Crystal Methamphetamine ◽  
Cross Sectional ◽  
Sexual Behaviours ◽  
Sex With Men ◽  
Exposure Prophylaxis ◽  
Hiv Negative

Men who have sex with men (MSM) who experience problematic chemsex are at high risk of acquiring HIV due to combined drug use and sexual behaviours. Pre-exposure prophylaxis (PrEP) could substantially reduce the risk of HIV transmission in this group of men. The aim of this study was to examine the biopsychosocial characteristics associated with PrEP use among HIV-negative MSM who have experienced problematic chemsex. This was a cross-sectional analysis of secondary data collected during client assessments at a specialist alcohol and drug service based within the United Kingdom. We compared the socio-demographics, substance use, sexual behaviours and mental health of MSM who reported ever using PrEP to those who reported never using PrEP. Statistical analysis was conducted using the Mann–Whitney U-test for continuous variables and Fisher’s exact test for categorical variables. Between August 2016 and July 2018, 165 HIV-negative MSM who engaged in chemsex had an assessment completed. Thirty-four per cent (n = 50/145) had ever used PrEP. The median age was 36 years (IQR: 30–42), 92% identified as gay (n = 152/165) and 79% were of white ethnicity (n = 130/164). The use of crystal methamphetamine was associated with higher levels of men ever using PrEP (40% versus 21%) (p= 0.047). Men who had ever used PrEP had a higher median number of sexual partners in the previous three months (20 versus 10) (p= 0.004) and had lower level of condom use in their sex lives (median reported 5% versus 50%) (p= 0.010) in comparison to men who had never used PrEP. It is encouraging that men having higher-risk sex had been accessing PrEP. However, further research is required to explore PrEP uptake, retention and adherence in this high-risk group.

scholarly journals Genomewide Linkage Screen for Waldenström Macroglobulinemia Susceptibility Loci in High-Risk Families

2006 ◽  
Vol 79 (4) ◽  
pp. 695-701 ◽  
Author(s):  
Mary L. McMaster ◽  
Lynn R. Goldin ◽  
Yan Bai ◽  
Monica Ter-Minassian ◽  
Stefan Boehringer ◽  
...  
Keyword(s):  
High Risk ◽  
Susceptibility Loci ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Genomewide Linkage ◽  
High Risk Families

Hevylite®, a New Marker of Tumor Measurement In Waldenstrom Macroglobulinemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5076-5076 ◽  
Author(s):  
Salomon Manier ◽  
Remy Dulery ◽  
Alain Duhamel ◽  
Eileen Boyle ◽  
Julien Rossignol ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Progressive Disease ◽  
Tumor Burden ◽  
M Protein ◽  
Advisory Committees ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
M Spike

Abstract Abstract 5076 Background. Waldenstrom macroglobulinemia (WM) is a low grade B cell lymphoma characterized by bone marrow infiltration of lymphoplasmacytic tumor cells that secrete monoclonal IgM (M-protein) into the serum. Measurement of the serum M-protein [using serum protein electrophoresis (SPEP)] and measurement of total IgM (using nephelometry) are used to diagnose and monitor WM. There are, however, many limitations with these techniques and new markers are needed. IgG and IgA Hevylite® immunoassays have been reported to be more sensitive than SPEP and nephelometry for identifying monoclonal immunoglobulins in multiple myeloma and unlike immunofixation, provide quantitative information. We hypothesized that serum IgM Hevylite assays (specifically measuring IgMkappa and IgMlambda, separately) would accurately identify serum IgM M-proteins. We also evaluated the association between known tumor burden markers and prognostic factors with IgM Hevylite results in patients with WM. Method. We retrospectively measured IgMkappa and IgMlambda in sera from 59 WM patients: 44 patients were at diagnosis and 15 had relapsed disease. The diagnosis of WM was made according to the current guidelines. All serum samples were kept frozen in the Lille serum bank since collection. All patients gave informed consent prior to the collection and none were treated at time of collection of the serum. Approval of this protocol was obtained from the CHRU Lille and was in accordance with the Declaration of Helsinki. Hevylite measurements were made at The Binding Site Ltd, Birmingham, UK. A normal range was produced from normal (blood donor) sera (n=120), median (and 95%ile ranges) were; IgMkappa 0.634g/L (0.29-1.82), IgMlambda 0.42g/L (0.17-0.94), IgMkappa/IgMlambda ratio 1.6 (0.95-2.3). For ease of comparison IgM hevylite ratios were expressed as the involved monoclonal immunoglobulin/uninvolved polyclonal immunoglobulin (IgMi). To describe the distribution of IgMi Hevylite levels in patients with WM, the median and range (min-max) were reported. Median values were compared using the Wilcoxon rank-sum test and ANOVA. Fisher's exact test was used to compare proportions. All statistical tests were two-sided. All analyses were conducted using SPSSv12 software. Results. The baseline characteristics of the patients were as follows: the median (range) age was 68 years (41-86), male/female 38/21, serum b2M 3.0mg/L (1.2-9.0), hemoglobin 11.8g/dL (7.6-15.4), platelet count 267 ×109/mm3 (55-741), serum M-spike 19g/L (3.0-52.7). In our series, 18 (31%), 22 (37%) and 19 (32%) patients had low, intermediate and high risk disease respectively, in the WM-IPSS scoring system. The median (min-max) IgMkappa ratio was 134 (8.7-2850) and IgMlambda ratio was 0.03 (0.0007-0.39). IgMi Hevylite ratio was 98.07 (2.59-2850). The IgMi Hevylite correlated well with the M-spike measured using SPEP (r=0.601, p<0.0001). In our study, high IgMi Hevylite levels correlated well with markers of high tumor burden and of poor prognosis. The median (range) IgMi Hevylite level was higher in patients with hemoglobin <10g/dL versus ≥10 g/dL, 267 (8.1-1722) and 76 (2.6-2850) respectively (p=0.013). The median (range) IgMi Hevylite ratio level was significantly (p=0.033) higher in the high risk IPSS group 208 (2.6-2850) than in the intermediate 75 (15-1033) and low risk groups, 98 (8-571). The IgMi Hevylite levels also separated WM patients with progressive disease who required therapy. Twenty seven pts were symptomatic and required specific treatment for WM, and 32 pts were left untreated. The median IgMi Hevylite ratio was significantly higher in progressing patients, 210 (8.1-2850) and 60 (2.6-571) in the 2 groups, respectively (p=0.014). Conclusion. In this study we demonstrated that IgM Hevylite measurement is a new and reliable marker for monitoring WM disease. It is related to poor prognostic markers that separate WM patients with progressive disease who require therapy. We are currently expanding the cohort to confirm these observations. These findings have implications in the management of patients with WM. Disclosures: Leblond: Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genzyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Leleu:Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

scholarly journals Progression Risk Stratification of Asymptomatic Waldenström Macroglobulinemia

2019 ◽  
Vol 37 (16) ◽  
pp. 1403-1411 ◽  
Author(s):  
Mark Bustoros ◽  
Romanos Sklavenitis-Pistofidis ◽  
Prashant Kapoor ◽  
Chia-Jen Liu ◽  
Efstathios Kastritis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Risk Group ◽  
Immunoglobulin M ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Progression Risk

BACKGROUND Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, β2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application ( www.awmrisk.com ). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.

scholarly journals A prognostic index predicting survival in transformed Waldenström macroglobulinemia

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Eric Durot ◽  
Lukshe Kanagaratnam ◽  
Saurabh Zanwar ◽  
Efstathios Kastritis ◽  
Shirley D’Sa ◽  
...  
Keyword(s):  
Rare Complication ◽  
International Prognostic Index ◽  
External Validation ◽  
Elevated Serum ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Data Set ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Histological Transformation

Histological transformation into diffuse large B-cell lymphoma is a rare complication in patients with Waldenström macroglobulinemia (WM) usually associated with a poor prognosis. The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates were identified as independent predictors of 2-year survival after transformation: elevated serum LDH (2 points), platelet count < 100 x 109/L (1 point) and any previous treatment for WM (1 point). Three risk groups were defined: low-risk (0-1 point, 24% of patients), intermediate-risk (2-3 points, 59%, hazard ratio (HR) = 3.4) and high-risk (4 points, 17%, HR = 7.5). Two-year survival rates were 81%, 47%, and 21%, respectively (P < 0.0001). This model appeared to be a better discriminant than the International Prognostic Index (IPI) and the revised IPI (R-IPI). We validated this model in an independent cohort. This easy-to-compute scoring index is a robust tool that may allow identification of groups of transformed WM patients with different outcomes and could be used for improving the development of risk-adapted treatment strategies.

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