Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenström Macroglobulinemia Treated With Nucleoside Analogs

2009 ◽  
Vol 27 (2) ◽  
pp. 250-255 ◽  
Author(s):  
Xavier Leleu ◽  
Jacob Soumerai ◽  
Aldo Roccaro ◽  
Evdoxia Hatjiharissi ◽  
Zachary R. Hunter ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Large Population ◽  
Nucleoside Analogs ◽  
Treated Group ◽  
High Grade ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Long Term Follow Up ◽  
Previously Treated

Purpose Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenström macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM. Patients and Methods We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years. Results Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months. Conclusion These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs.

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.

scholarly journals Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients With Waldenström Macroglobulinemia

2020 ◽  
pp. JCO.20.00555
Author(s):  
Steven P. Treon ◽  
Kirsten Meid ◽  
Joshua Gustine ◽  
Guang Yang ◽  
Lian Xu ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Response Rates ◽  
Immunoglobulin M ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Major Response ◽  
Previously Treated Patients ◽  
Previously Treated

PURPOSE We report the long-term findings and final analysis of a pivotal multicenter trial of ibrutinib monotherapy in previously treated patients with Waldenström macroglobulinemia (WM). PATIENTS AND METHODS Sixty-three symptomatic patients with median prior therapies of two (range, one to nine therapies), of whom 40% were refractory to their previous therapy, received ibrutinib at 420 mg/d. Dose reduction was permitted for toxicity. RESULTS The median follow-up was 59 months, and overall and major response rates were 90.5% and 79.4%, respectively. At best response, median serum immunoglobulin M declined from 3,520 to 821 mg/dL, bone marrow disease involvement declined from 60% to 20%, and hemoglobin rose from 10.3 to 14.2 g/dL ( P < .001 for all comparisons). Responses were impacted by mutated (Mut) MYD88 and CXCR4 status. Patients with MYD88Mut, wild-type (WT) CXCR4 showed higher major (97.2% v 68.2%; P < .0001) and very good partial (47.2% v 9.1%; P < .01) response rates and a shorter time to major response (1.8 v 4.7 months; P = .02) versus patients with MYD88Mut CXCR4Mut. Conversely, four patients who had MYD88WT disease showed no major responses. The median 5-year progression-free survival (PFS) rate for all patients was not reached, and was 70% and 38% for those with MYD88Mut CXCR4WT and MYD88Mut CXCR4Mut WM, respectively ( P = .02). In patients with MYD88WT, the median PFS was 0.4 years ( P < .01 for three-way comparisons). The 5-year overall survival rate for all patients was 87%. Grade ≥ 3 adverse events in more than one patient at least possibly related included neutropenia (15.9%), thrombocytopenia (11.1%), and pneumonia (3.2%). Eight patients (12.7%) experienced atrial arrhythmia, and seven of the eight continued therapy with medical management. CONCLUSION Ibrutinib is highly active and produces long-term disease control in previously treated patients with WM. Treatment is tolerable. Response depth, time to major response, and PFS are impacted by MYD88 and CXCR4 mutation status.

scholarly journals Long-term follow-up of symptomatic patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia treated with the anti-CD52 monoclonal antibody alemtuzumab

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 276-281 ◽  
Author(s):  
Steven P. Treon ◽  
Jacob D. Soumerai ◽  
Zachary R. Hunter ◽  
Christopher J. Patterson ◽  
Leukothea Ioakimidis ◽  
...  
Keyword(s):  
Late Onset ◽  
Treatment Options ◽  
Complete Response ◽  
Infectious Complications ◽  
Lymphoplasmacytic Lymphoma ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Long Term Follow Up

Abstract CD52 is expressed on malignant cells in lymphoplasmacytic lymphoma (LPL), including IgM-secreting Waldenström macroglobulinemia (WM). We examined the activity of alemtuzumab in 28 symptomatic LPL (27 IgM and 1 IgA) patients. The median prior number of therapies for these patients was 2 (range, 0-5) and 43% had refractory disease. Patients received alemtuzumab at 30 mg IV 3 times weekly for up to 12 weeks after test dosing, and also received hydrocortisone, acyclovir, and Bactrim or equivalent prophylaxis. Patients had a complete response (n = 1), a partial response (n = 9), or a MR (n = 11) for an overall and major response rate of 75% and 36%, respectively. Median serum Ig decreased from 3510 to 1460 mg/dL (P < .001 at best response). With a median follow-up of 64 months, the median time to progression was 14.5 months. Hematologic and infectious complications, including CMV reactivation, were more common in previously treated patients and were indirectly associated with 3 deaths. Long-term follow-up revealed late-onset autoimmune thrombocytopenia (AITP) in 4 patients at a median of 13.6 months after therapy, which contributed to 1 death. Alemtuzumab is an active therapy in patients with LPL, but short- and long-term toxicities need to be carefully weighed against other available treatment options. Late AITP is a newly recognized complication of alemtuzumab in this patient population. This study is registered at www.clinicaltrials.gov as NCT00142181.

scholarly journals Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Robert J. Kreitman ◽  
◽  
Claire Dearden ◽  
Pier Luigi Zinzani ◽  
Julio Delgado ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Braf Inhibitor ◽  
Nucleoside Analogs ◽  
High Rate ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Long Term Follow Up

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

Long-Term Follow-up of Patients with Stage T1 High-Grade Transitional Cell Carcinoma Managed by Bacille Calmette-Guérin Immunotherapy

Urology ◽  
2007 ◽  
Vol 69 (1) ◽  
pp. 78-82 ◽  
Author(s):  
David Margel ◽  
Raanan Tal ◽  
Shai Golan ◽  
Dani Kedar ◽  
Dov Engelstein ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Transitional Cell ◽  
High Grade ◽  
Bacille Calmette Guerin ◽  
Long Term Follow Up ◽  
Stage T1

The transvenous retrograde pressure cooker technique for the curative embolization of high-grade brain arteriovenous malformations

2020 ◽  
pp. neurintsurg-2020-016566
Author(s):  
Masaomi Koyanagi ◽  
Pascal John Mosimann ◽  
Hannes Nordmeyer ◽  
Markus Heddier ◽  
Juergen Krause ◽  
...  
Keyword(s):  
Arteriovenous Malformations ◽  
High Grade ◽  
Transvenous Embolization ◽  
Cure Rate ◽  
Brain Arteriovenous Malformations ◽  
Long Term Follow Up ◽  
Occlusion Rate ◽  
Grade 3

BackgroundTransvenous embolization of brain arteriovenous malformations (AVMs) can be curative. We aimed to evaluate the cure rate and safety of the transvenous retrograde pressure cooker technique (RPCT) using coils and n-butyl-2-cyanoacrylate as a venous plug.MethodsAll AVM patients treated via transvenous embolization between December 2004 and February 2017 in a single center were extracted from our database. Inclusion criteria were: inability to achieve transarterial cure alone; AVM < 3 cm; and single main draining vein. Outcome measures were immediate and 90 days' angiographic AVM occlusion rate, and morbidity and mortality at 30 days and 12 months, according to the modified Rankin Scale (mRS) score.ResultsFifty-one patients (20 women; median age 47 years) were included. A majority (71%) were high grade (3 to 5 in the Spetzler–Martin classification). AVMs were deeply seated in 30 (59%) and cortical in 21 patients (41%). Thirty-three patients were previously embolized transarterially (65%). All patients but one were cured within a single session with the RPCT (96%). Cure was confirmed on follow-up digital subtraction angiography at 3 months in 82% of patients. Three patients experienced intracranial hemorrhage (6%), one requiring surgical evacuation. There were no deaths. One treatment-related major permanent deficit was observed (2.0%). Mean mRS before treatment, at 30 days, and 12 months after RPCT was 1.5, 1.5, and 1.3, respectively.ConclusionsThe retrograde pressure cooker technique can be curative in carefully selected high-grade AVMs. Long-term follow-up and prospective studies are needed to confirm our results.

P2871Attenuated clinical benefit after ICD replacement over long term follow-up in a contemporary large world population: insight to the DECODE registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Zanon ◽  
E Menardi ◽  
E Ammendola ◽  
P De Filippo ◽  
M Manzo ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Cox Regression ◽  
Electronic Device ◽  
Large Population ◽  
World Population ◽  
Italian Population ◽  
Cox Regression Analysis ◽  
Long Term Follow Up

Abstract Background Cardiac Implantable Electronic Device (CIED) surgery is threatened by serious complications both during the procedure and during follow-up. The factors associated to attenuated clinical benefit over long term follow-up are poorly understood. Purpose To evaluate type and extent of Adverse Events (AEs) and potential predictors of major AEs over 12 months after ICD/CRT-D replacement/upgrade in a contemporary Italian population. Methods Detect long-term complications after ICD replacement (DECODE) was a prospective, single-arm, multicenter cohort study aimed at estimating medium- to long-term complications in a large population of patients (pts) who underwent ICD/CRT-D replacement/upgrade from 2013 to 2015. The endpoint for this analysis is death from any cause, procedure-related infection, and surgical actions/hospitalizations necessary to treat the AEs. Results We included 983 consecutive pts (median age 71 years, 76% male, 55% ischemic, 47% CRT-D). During a mean follow-up duration of 353±49 days, 7% of the pts died. A total of 104 AEs occurred in 70 (7.1%) pts. 43 (4.4%) pts needed at least one surgical action to treat the AEs. A total of 23 (2.3%) pts had infective AEs (CIED related in 12 pts, due to other causes in 11). Mortality was unrelated to the occurrence of overall AEs, or of CIED-related AEs, or of surgical actions/hospitalizations needed to correct AEs. The endpoint was reached by 109 (11%) pts over 12-month follow-up (97 pts had a single event, and 12 pts had two events). The median time to the endpoint was 137 [50 - 254] days. On multivariate Cox regression analysis adjusted for baseline confounders, ischemic cardiomyopathy (HR = 1.86, 95% CI: 1.18 to 2.91; p=0.0076), hospitalization prior to the procedure (2.34, 1.35 to 4.05; 0.0025) and anticoagulation (1.91, 1.25 to 2.92; 0.0032) were associated with the endpoint during follow-up. Conclusion Evaluation of the patient's profile may assist in predicting vulnerability and should prompt reconsideration of the procedure by deferring at a more stable clinical status, and carefully individualized in the setting of upgrades and anticoagulation management Acknowledgement/Funding None

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