Prognostic impact of <i><scp>MYD88</scp></i> and <i><scp>CXCR4</scp></i> mutations assessed by droplet digital polymerase chain reaction in <scp>IgM</scp> monoclonal gammopathy of undetermined significance and smouldering Waldenström macroglobulinaemia

Moreno, David F.; López‐Guerra, Mònica; Paz, Sara; Oliver‐Caldés, Aina; Mena, M.T. Miana; Correa, Juan Gonzalo; Battram, Anthony M.; Osuna, Miguel; Rivas‐Delgado, Alfredo; Rodríguez‐Lobato, Luis Gerardo; Cardus, Oriol; Tovar, Natalia; Cibeira, María Teresa; Jiménez‐Segura, Raquel; Bladé, Joan; Rosiñol, Laura; Colomer, Dolors; Larrea, Carlos Fernández de

doi:10.1111/bjh.18502

Cited by 16 publications

(1 citation statement)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a retrospective analysis of 54 patients from the FIL_BIOWM study they have demonstrated, for the rst time, that molecular remission is an independent predictor of PFS. Droplet digital polymerase chain reaction (ddPCR) assays for MYD88 have also been described 21,22 and may ultimately provide a reproducible platform for more widespread and routine use. They have been successfully used in a post-treatment pilot assessment, although no outcome data is yet available.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia

de Tute,

Counsell,

Clifton-Hadley

et al. 2024

Leukemia

View full text Add to dashboard Cite

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrőm macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-speci c ow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response. Sixty treatment-naïve WM patients were enrolled into this phase II trial and randomised (2:1) to receive cyclophosphamide and rituximab with either bortezomib (BCR) or udarabine (FCR). The primary objective was to assess the overall response rate (ORR) in eligible patients receiving BCR (N=41). An ORR of 97.6% (95%CI: 87.1-99.9) was observed; 27 (65.9%) patients remain alive without progression after 62.6 months median follow-up, with 2-and 3-year progression-free survival (PFS) rates of 92.7% (95%CI: 79.0-97.6) and 80.5% (95%CI: 64.8-89.7). Persistent WM B-cells were demonstrable in 19/38 patients at the end of treatment (median 0.24%, range 0.02-11.2%). PFS was markedly longer in patients with BM B-cell depletion (<0.004%) compared to those who had persistent BM B-cells detectable at end of treatment (HR=0.06, 95%CI:0.01-0.47, p<0.001), and remained independently associated after adjusting for baseline risk strati cation or investigator-assessed response. BCR is a tolerable, highly e cacious regimen for treatment-naïve WM patients. BM B-cell depletion is independently associated with patient outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia

de Tute,

Counsell,

Clifton-Hadley

et al. 2024

Leukemia

View full text Add to dashboard Cite

show abstract

Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry

Moreno,

Jiménez,

Escalante

et al. 2024

HemaSphere

View full text Add to dashboard Cite

Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow‐up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2‐microglobulin ≥3 mg/L, and albumin <4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low‐, intermediate‐, and high‐risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of MYD88 L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5‐year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.

show abstract

Impact of chromosomal aberrations detected by chromosome banding analysis in symptomatic Waldenström’s macroglobulinemia

Ito,

Kitagawa,

Harada

et al. 2024

Ann Hematol

View full text Add to dashboard Cite

Prognostic impact of MYD88 and CXCR4 mutations assessed by droplet digital polymerase chain reaction in IgM monoclonal gammopathy of undetermined significance and smouldering Waldenström macroglobulinaemia

Cited by 16 publications

References 38 publications

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia

Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry

Impact of chromosomal aberrations detected by chromosome banding analysis in symptomatic Waldenström’s macroglobulinemia

Contact Info

Product

Resources

About