Pentostatin, cyclophosphamide and rituximab is a safe and effective treatment in patients with Waldenström’s macroglobulinemia

Herth, Isabelle; Hensel, Manfred; Rieger, Michael A.; Horstmann, Kristin; Hiddemann, Wolfgang; Dreyling, Martin; Koniczek, Silvia; Witzens-Harig, Mathias; Ho, Anthony D.

doi:10.3109/10428194.2014.911869

Cited by 12 publications

(20 citation statements)

References 29 publications

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“…Cladribine results in an overall response rate of 88%, with no difference in risk categories 45 . Pentostatin produced a two-year, progression-free survival of 83.6% 46 .…”

Section: Therapy Of Waldenström Macroglobulinemiamentioning

confidence: 97%

Waldenström macroglobulinemia treatment algorithm 2018

Gertz

2018

Blood Cancer J.

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Waldenström macroglobulinemia is often an indolent disorder, and many patients are candidates for observation with careful monitoring. For symptomatic patients, one must distinguish between those patients whose symptoms are related to immunologic manifestations associated with the IgM monoclonal protein and those that have symptoms related to progressive marrow and nodal infiltration with lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, the driver for therapy in the majority of patients is progressive anemia, secondary to bone marrow replacement by lymphoplasmacytic lymphoma. Recent introduction of MYD88 mutational analysis has been very useful for diagnostic purposes but is unclear what effect it might have on the prognosis or response rate to therapy. An algorithm is provided on the management of asymptomatic individuals and the sequence used for chemotherapeutic intervention of symptomatic patients.

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“…Cladribine results in an overall response rate of 88%, with no difference in risk categories 45 . Pentostatin produced a two-year, progression-free survival of 83.6% 46 .…”

Section: Therapy Of Waldenström Macroglobulinemiamentioning

confidence: 97%

Waldenström macroglobulinemia treatment algorithm 2018

Gertz

2018

Blood Cancer J.

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“…Our results fill an important gap in the knowledge regarding optimal frontline treatment of WM/LPL. Rituximab‐based regimens are now universally endorsed on the basis of high response rates (85–95%) derived from single‐arm studies and one randomized trial (Gertz et al , ; Treon et al , ; Dimopoulos et al , ; Buske et al , ; Herth et al , ). In that trial, 64 patients received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy with or without rituximab.…”

Section: Discussionmentioning

confidence: 99%

Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia

et al. 2017

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Comparative data on immunochemotherapy regimens for Waldenström macroglobulinaemia/lymphoplasmacytic lymphoma (WM/LPL) are lacking. We analysed overall survival (OS), risk of hospitalizations, transfusions and plasmapheresis in a population-based cohort of patients ≥65 years old initiating WM/LPL therapy in 1999-2013. To minimize bias, we applied a propensity score-based causal inference method. We conducted three analyses of: patients treated with or without rituximab, patients treated with rituximab monotherapy or with combination immunochemotherapy, and regimens based on classic purine analogues or alkylators. Among 1310 patients, 78·5% received rituximab. Patients who received rituximab had significantly better OS [hazard ratio (HR) 0·62, 95% confidence interval (CI) 0·55-0·71] and lower risk of transfusions (risk difference -3·3%, 95% CI -6·3 to -0·3) than those who did not, without a significant difference in hospitalizations or plasmapheresis. We observed no significant difference in OS (HR 0·91, 95% CI 0·79-1·04) between rituximab monotherapy and combination immunochemotherapy, but toxicity outcomes were lower with rituximab alone. Neither survival (HR 1·10, 95%CI 0·92-1·32) nor toxicity outcomes differed significantly between regimens based on purine analogues or alkylators. The survival advantage strongly supports rituximab as part of upfront therapy for WM/LPL, whereas regimens with either purine analogues or alkylating agents result in similar outcomes.

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“…Purine nucleoside analogs should not be forgotten in the salvage therapy of WM. Long term myelosuppression with FCR and the higher infection rate with fludarabine make it a consideration for third line therapy …”

Section: Managementmentioning

confidence: 99%

Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management

Gertz

2018

American J Hematol

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Disease Overview Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in >90% of patients and is found in the majority of IgM monoclonal gammopathy of undetermined significance patients. Risk Stratification Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Risk‐Adapted Therapy Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‐monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogs are active but usage is declining for less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine. Potential for stem cell transplantation should be considered in selected younger patients. Management of Refractory Disease Bortezomib, fludarabine, thalidomide, everolimus, ibrutinib, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection.

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Pentostatin, cyclophosphamide and rituximab is a safe and effective treatment in patients with Waldenström’s macroglobulinemia

Cited by 12 publications

References 29 publications

Waldenström macroglobulinemia treatment algorithm 2018

Waldenström macroglobulinemia treatment algorithm 2018

Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia

Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management

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