scholarly journals WALDENSTROM’S MACROGLOBULINEMIA: AN UPDATE

2018 ◽  
Vol 10 ◽  
pp. e2018004 ◽  
Author(s):  
Maddalena Mazzucchelli ◽  
Anna Maria Frustaci ◽  
Marina Deodato ◽  
Roberto Cairoli ◽  
Alessandra Tedeschi
Keyword(s):  
Stem Cell ◽  
Molecular Markers ◽  
Lymphoproliferative Disorder ◽  
Clinical Presentation ◽  
Secondary Malignancies ◽  
Waldenström Macroglobulinemia ◽  
Disease Characteristics ◽  
Waldenstrom Macroglobulinemia ◽  
Mutational Status ◽  
Risk Of Treatment

Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with distinctive clinical features.Diagnostic and prognostic charactrization in WM significantly changed with the discovery of two molecular markers: MYD88 and CXCR4. Mutational status of these latter influences both clinical presentation and prognosis and demonstrated therapeutic implications.Treatment choice in Waldemstrom disease is strictly guided by patients age and characteristics, specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, disease characteristics, risk of immunosuppression or secondary malignancies and potential for future autologous stem cell transplantation.Therapeutic landscape has expanded during the last years and the approval of ibrutinib, the first drug approved for Waldenstrom Macroglobulinemia, represents an important step forward for a better management of the disease. 

scholarly journals Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial

2020 ◽  
Vol 4 (23) ◽  
pp. 6009-6018
Author(s):  
Meletios Dimopoulos ◽  
Ramon Garcia Sanz ◽  
Hui-Peng Lee ◽  
Marek Trneny ◽  
Marzia Varettoni ◽  
...  
Keyword(s):  
Partial Response ◽  
Progression Free Survival ◽  
Waldenström Macroglobulinemia ◽  
Activating Mutations ◽  
Waldenstrom Macroglobulinemia ◽  
Mutational Status ◽  
Major Response ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Poor Outcomes

Abstract Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naïve) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.

Incidence of secondary malignancies among patients with Waldenström macroglobulinemia: An analysis of the SEER database

Cancer ◽  
2015 ◽  
Vol 121 (13) ◽  
pp. 2230-2236 ◽  
Author(s):  
Jorge J. Castillo ◽  
Adam J. Olszewski ◽  
Zachary R. Hunter ◽  
Sandra Kanan ◽  
Kirsten Meid ◽  
...  
Keyword(s):  
Secondary Malignancies ◽  
Seer Database ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia

scholarly journals Ixazomib, dexamethasone, and rituximab in treatment-naive patients with Waldenström macroglobulinemia: long-term follow-up

2020 ◽  
Vol 4 (16) ◽  
pp. 3952-3959
Author(s):  
Jorge J. Castillo ◽  
Kirsten Meid ◽  
Catherine A. Flynn ◽  
Jiaji Chen ◽  
Maria G. Demos ◽  
...  
Keyword(s):  
Median Time ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Mutational Status ◽  
Long Term Follow Up ◽  
Treatment Naïve

Abstract Proteasome inhibition is a standard of care for the primary treatment of patients with Waldenström macroglobulinemia (WM). We present the long-term follow-up of a prospective, phase II clinical trial that evaluated the combination of ixazomib, dexamethasone, and rituximab (IDR) in 26 treatment-naive patients with WM. IDR was administered as 6 monthly induction cycles followed by 6 every-2-month maintenance cycles. The MYD88 L265P mutation was detected in all patients, and CXCR4 mutations were detected in 15 patients (58%). The median time to response (TTR) and time to major response (TTMR) were 2 and 6 months, respectively. Patients with and without CXCR4 mutations had median TTR of 3 months and 1 month, respectively (P = .003), and median TTMR of 10 months and 3 months, respectively (P = .31). The overall, major, and very good partial response (VGPR) rates were 96%, 77%, and 19%, respectively. The rate of VGPR in patients with and without CXCR4 mutations were 7% and 36%, respectively (P = .06). The median progression-free survival (PFS) was 40 months, the median duration of response (DOR) was 38 months, and the median time to next treatment (TTNT) was 40 months. PFS, DOR, and TTNT were not affected by CXCR4 mutational status. The safety profile was excellent with no grade 4 adverse events or deaths to date. IDR provides a safe and effective frontline treatment option for symptomatic patients with WM. This study was registered at www.clinicaltrials.gov as #NCT02400437.

Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenström macroglobulinemia

Blood ◽  
2014 ◽  
Vol 123 (18) ◽  
pp. 2791-2796 ◽  
Author(s):  
Steven P. Treon ◽  
Yang Cao ◽  
Lian Xu ◽  
Guang Yang ◽  
Xia Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Somatic Mutations ◽  
Clinical Presentation ◽  
Hyperviscosity Syndrome ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Key Points

Key Points Activating MYD88 as well as nonsense and frameshift WHIM-like CXCR4 somatic mutations are common in WM. CXCR4 NS mutations are present in aggressive cases including hyperviscosity syndrome, and MYD88 status is a determinant of survival.

Waldenström macroglobulinemia

2013 ◽  
Vol 154 (50) ◽  
pp. 1970-1974
Author(s):  
Béla Telek ◽  
Péter Batár ◽  
László Váróczy ◽  
Lajos Gergely ◽  
László Rejtő ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Clinical Symptoms ◽  
Alkylating Agents ◽  
Lymphoproliferative Disease ◽  
Therapeutic Approaches ◽  
Purine Analogues ◽  
Detailed Review ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia

Waldenström macroglobulinemia is a rare lymphoproliferative disease of B-cell origin.These tumorous B-cells produce monoclonal IgM type protein. Diagnosis is based on the detection of lymphoplasmacytic invasion of the bone marrow and serum electrophoresis. Clinical symptoms such as anemia, hyperviscosity and neuropathy are the commom consequences of bone marrow infiltration and serum monoclonal IgM protein. Former use of alkylating agents are replaced by purine analogues, rituximab and bortezomib. Additional clinical data have also accumulated regarding autologous and allogenous stem-cell transplantation. The authors present their own clinical experience and give a detailed review of current therapeutic approaches. Orv. Hetil., 154(50), 1970–1974.

Sign in / Sign up

Export Citation Format

Share Document