Dataset Information

Long-term outcomes to fludarabine and rituximab in Waldenstrom macroglobulinemia.

ABSTRACT: We report the long-term outcome of a multicenter, prospective study examining fludarabine and rituximab in Waldenström macroglobulinemia (WM). WM patients with less than 2 prior therapies were eligible. Intended therapy consisted of 6 cycles (25 mg/m(2) per day for 5 days) of fludarabine and 8 infusions (375 mg/m(2) per week) of rituximab. A total of 43 patients were enrolled. Responses were: complete response (n = 2), very good partial response (n = 14), partial response (n = 21), and minor response (n = 4), for overall and major response rates of 95.3% and 86.0%, respectively. Median time to progression for all patients was 51.2 months and was longer for untreated patients (P = .017) and those achieving at least a very good partial response (P = .049). Grade 3 or higher toxicities included neutropenia (n = 27), thrombocytopenia (n = 7), and pneumonia (n = 6), including 2 patients who died of non-Pneumocystis carinii pneumonia. With a median follow-up of 40.3 months, we observed 3 cases of transformation to aggressive lymphoma and 3 cases of myelodysplastic syndrome/acute myeloid leukemia. The results of this study demonstrate that fludarabine and rituximab are highly active in WM, although short- and long-term toxicities need to be carefully weighed against other available treatment options. This study is registered at clinicaltrials.gov as NCT00020800.

SUBMITTER: Treon SP

PROVIDER: S-EPMC2670786 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Long-term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia.

Treon Steven P SP Branagan Andrew R AR Ioakimidis Leukothea L Soumerai Jacob D JD Patterson Christopher J CJ Turnbull Barry B Wasi Parveen P Emmanouilides Christos C Frankel Stanley R SR Lister Andrew A Morel Pierre P Matous Jeffrey J Gregory Stephanie A SA Kimby Eva E

Blood 20081117 16

We report the long-term outcome of a multicenter, prospective study examining fludarabine and rituximab in Waldenström macroglobulinemia (WM). WM patients with less than 2 prior therapies were eligible. Intended therapy consisted of 6 cycles (25 mg/m(2) per day for 5 days) of fludarabine and 8 infusions (375 mg/m(2) per week) of rituximab. A total of 43 patients were enrolled. Responses were: complete response (n = 2), very good partial response (n = 14), partial response (n = 21), and minor res ...[more]

PMID: 19015393

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Project description:PurposeWe 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 methodsSixty-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.ResultsThe 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 MYD88MutCXCR4Mut. 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 MYD88MutCXCR4WT and MYD88MutCXCR4Mut 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.ConclusionIbrutinib 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.

Project description:Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM) is a rare lymphoma affecting older patients. Its management largely relies on small phase II trials and it is unclear how their results translate into clinical practice in the community.We evaluated changes in the presentation, management, and survival among 2,666 Medicare beneficiaries diagnosed with WM between 1994 and 2011, using Medicare claims linked to Surveillance, Epidemiology and End Results data.Prevalence of transfusions, anemia, thrombocytopenia, and neuropathy at diagnosis significantly increased over time, whereas the use of plasmapheresis was low (2.5%) and stable. The proportion of patients starting chemotherapy within 1 year of WM diagnosis increased from 39% in 1994 to 62% in 2011 (p < .0001). Treatments based on classic alkylators and purine analogs predominated in the 1990s, but were quickly replaced by rituximab-containing regimens after 2000. Rituximab monotherapy has been prescribed for >50% of patients since 2004, and combination chemoimmunotherapy for a further 30%. Most patients initiating multiagent regimens in 2012-2013 received rituximab with bortezomib or bendamustine. These changes were accompanied by significant improvements in overall and WM-related survival, but also by a significant increase in cost of chemotherapy. Mean Medicare payments for chemotherapy drugs accrued in the first year of treatment rose from $9,464 in 1994-2000 to $29,490 after 2008.Hematologists have rapidly adopted innovative, expensive therapies for WM before completion of randomized trials. This underscores the need to assess the comparative value of such therapies in rare malignancies through a combination of clinical and observational data.Most older patients with Waldenström macroglobulinemia currently treated in the U.S. receive rituximab as monotherapy or in combination with bortezomib or bendamustine. Newly designed trials should consider control arms aligned with this prevalent real-life standard. Compared with the 1990s, patients diagnosed according to current criteria are more likely to have anemia or neuropathy, or to receive early chemotherapy, but only 2.5% require plasmapheresis at diagnosis. The incremental clinical value of newly introduced agents needs to be assessed through a combination of clinical and health services research, taking into consideration their associated survival benefits, toxicities, and associated costs of care.

Dataset Information

Long-term outcomes to fludarabine and rituximab in Waldenstrom macroglobulinemia.

Publications

Long-term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia.

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