Treatment of Waldenstrom’s Macroglobulinemia With Thalidomide

PURPOSE: We performed a prospective phase II study to assess the activity of thalidomide in patients with Waldenstrom’s macroglobulinemia (WM). PATIENTS AND METHODS: Twenty patients with WM were treated with thalidomide at a starting dose of 200 mg daily with dose escalation in 200-mg increments every 14 days as tolerated to a maximum of 600 mg. All patients were symptomatic, their median age was 74 years, and 10 patients were previously untreated. RESULTS: On an intent-to-treat basis, five (25%) of 20 patients achieved a partial response after treatment. Responses occurred in three of 10 previously untreated and in two of 10 pretreated patients. None of the patients treated during refractory relapse or with disease duration exceeding 2 years responded to thalidomide. Time to response was short, ranging between 0.8 months to 2.8 months. Adverse effects were common but reversible and consisted primarily of constipation, somnolence, fatigue, and mood changes. The daily dose of thalidomide was escalated to 600 mg in only five patients (25%), and in seven patients (35%), this agent was discontinued within 2 months because of intolerance. CONCLUSION: Our data indicate that thalidomide has activity in WM but only low doses were tolerated in this elderly patient population. Confirmatory studies as well as studies that will combine thalidomide with chemotherapy or with rituximab may be relevant.

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Combination Therapy with Rituximab and Fludarabine in Waldenstrom’s Macroglobulinemia.

Blood ◽

10.1182/blood.v104.11.753.753 ◽

2004 ◽

Vol 104 (11) ◽

pp. 753-753 ◽

Cited By ~ 3

Author(s):

Steven P. Treon ◽

Andrew Branagan ◽

Parveen Wasi ◽

Christos A. Emmanouilides ◽

Stanley R. Frankel ◽

...

Keyword(s):

Fold Increase ◽

Secondary Malignancy ◽

Subdural Hemorrhage ◽

Low Grade ◽

Waldenström’S Macroglobulinemia ◽

Highly Active ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Intent To Treat ◽

Waldenström's Macroglobulinemia

Abstract Rituximab and Fludarabine are active in Waldenstrom’s macroglobulinemia (WM) producing major response rates of 40–70%. Both pre-clinical and clinical studies in related low-grade B-cell malignancies suggest that additive, and even synergistic benefit with combination Fludarabine and Rituximab may result. As such, we conducted this combination study with Rituximab and Fludarabine in WM patients. WM patients who had received < 2 prior therapies, and who had not previously been treated with any nucleoside analogue or Rituximab were eligible. Intended therapy was as follows: Weeks 1–4 Rituximab (375 mg/m2/week) Weeks 5, 9, 13 Fludarabine daily for 5 days (25 mg/m2) Weeks 17, 18 Rituximab (375 mg/m2/week) Weeks 19, 23, 27 Fludarabine daily for 5 days (25 mg/m2) Week 30, 31 Rituximab (375 mg/m2/week) Patients were evaluated at week 12, and if they did not progress were eligible for further therapy and were evaluable for response. 43 WM patients were enrolled with a median age of 61 (range 52–75 yrs), and median prior therapies of 1 (range 0–2). 40/43 patients continued on therapy beyond week 12. Two patients (1 PR, 1 SD) died after completing protocol therapy including one elderly patient who had an influenza pneumonia and another debilitated patient who may have had a secondary malignancy. Delays in therapy due to neutropenia were common, and 58% of patients experienced Grade III/IV neutropenia. Protocol therapy was truncated after the 4th and 5th courses of fludarabine in several patients for persistent neutropenia and/or thrombocytopenia despite delays in therapy and/or use of G-CSF support. Other complications included: Herpes zoster outbreak in 3 of the first 21 patients, before prophylactic acyclovir or equivalent was initiated; parasthesias (n=3); pneumonitis (n=2); development of bladder cancer (n=1) and a high grade lymphoma (n=1); subdural hemorrhage in a patient who had a 3-fold increase in serum viscosity following the first 4 infusions of Rituximab. On an intent to treat basis, 39/43 (90.1%) patients demonstrated a response. Response categories were as follows: CR (n=3); PR (n=32); MR (n=4). One patient remains in stable disease at 20+ months. At a median follow-up of 17 months, 36 of 39 responding patients remain in remission. Rituximab in combination with fludarabine is highly active and produces durable responses in WM.

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Waldenstrom's macroglobulinemia with peripheral neuropathy and favorable long-term treatment responses

Medicine: Case Reports and Study Protocols ◽

10.1097/md9.0000000000000111 ◽

2021 ◽

Vol 2 (6) ◽

pp. e0111

Author(s):

Mary Lou Anne Y. Cabacang ◽

Raymond L. Rosales

Keyword(s):

Peripheral Neuropathy ◽

Term Treatment ◽

Waldenström’S Macroglobulinemia ◽

Long Term Treatment ◽

Waldenstrom's Macroglobulinemia ◽

Treatment Responses ◽

Waldenstrom’S Macroglobulinemia ◽

Waldenström's Macroglobulinemia

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Imatinib Mesylate (Gleevec®) Is Active in Relapsed/Refractory Waldenstrom’s Macroglobulinemia: Planned Interim Results of WMCTG Clinical Trial 05-140.

Blood ◽

10.1182/blood.v108.11.2484.2484 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2484-2484

Author(s):

Steven P. Treon ◽

Jacob D. Soumerai ◽

Christopher J. Patterson ◽

Zachary R. Hunter ◽

Rose Villarreal ◽

...

Keyword(s):

Imatinib Mesylate ◽

Waldenström’S Macroglobulinemia ◽

Growth And Survival ◽

Best Response ◽

Median Serum ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Intent To Treat ◽

Waldenström's Macroglobulinemia ◽

Cell Disorder

Abstract Waldenstrom’s macroglobulinemia is a B-cell disorder characterized by the infiltration of lymphoplasmacytic cells (LPC) in the bone marrow (BM), along with an IgM monoclonal gammopathy. Characteristic of WM is an increased number of mast cells (MC) which are found in association with LPC, and stimulate LPC growth through several TNF-family members including CD40L, APRIL and BLYS (Ann Oncol17:1275; Blood104:917A). As such, we have targeted MC in WM. One important growth and survival factor for MC is stem cell factor (SCF), which signals through CD117. Imatinib mesylate blocks SCF signaling through CD117, and induces apoptosis of WM BM MC and LPC, both of which highly express CD117 (Blood2004; 104:314b). As such, we performed this Phase II study of imatinib mesylate in patients with relapsed and refractory WM. Intended therapy consisted of imatinib mesylate which was initiated at 400 mg po qD over the first month, and subsequently dose escalated to 600 mg po qD for up to 2 years. Dose de-escalation to 300 mg po qD was permitted for toxicity. Thirteen patients were enrolled and are eligible for evaluation at interim analysis. Median age was 64 (range 53–80 years), and median prior therapies was 2 (range 1–5). Nine and four patients had relapsed and refractory disease, respectively. Following a median of 3 months of therapy, median serum IgM levels for all evaluable patients declined from 3190 (range 763–8130 mg/dL) to 2095 (range 695–7340 mg/dL) at best response (p=0.009). On an intent to treat analysis, 6/13 (46.2%) of patients attained a ≥25% decrease in serum IgM. Responses were prompt, and occurred at a median of 2.5 months. Overall, therapy was well tolerated with ≥grade 2 toxicities as follows: anemia (n=4); edema (n=3); hyperglycemia (n=2); leukopenia (n=2); thrombocytopenia (n=1); neutropenia (n=1); and resulted for 4 patients in dose modification (n=4) or treatment cessation (n=3). The interim results of this study demonstrate that imatinib mesylate is an active and well-tolerated salvage therapy for WM.

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Treatment of Waldenström’s Macroglobulinemia With Rituximab

Journal of Clinical Oncology ◽

10.1200/jco.2002.09.039 ◽

2002 ◽

Vol 20 (9) ◽

pp. 2327-2333 ◽

Cited By ~ 179

Author(s):

Meletios A. Dimopoulos ◽

Constantinos Zervas ◽

Athanassios Zomas ◽

Christos Kiamouris ◽

Nora A. Viniou ◽

...

Keyword(s):

Median Time ◽

Immunoglobulin M ◽

Low Grade ◽

Waldenström’S Macroglobulinemia ◽

Duration Of Response ◽

Pretreated Patients ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Anti Cd20 ◽

Waldenström's Macroglobulinemia

PURPOSE: Waldenström’s macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma in which CD20 is usually expressed on tumor cells. There is evidence that patients with WM may benefit from treatment with the anti-CD20 monoclonal antibody rituximab. We performed a prospective phase II study to clearly define the activity of rituximab in patients with this disease. PATIENTS AND METHODS: Twenty-seven patients with WM were treated with rituximab 375 mg/m2 intravenously (IV) for 4 weeks. Three months after completion of rituximab, patients without evidence of progressive disease received repeat 4-week courses of this agent. All patients were symptomatic, their median age was 72 years, and 15 patients were previously untreated. RESULTS: Twelve patients (44%; 95% confidence interval, 25.5% to 64.7%) achieved a partial response after treatment with rituximab. Median time to response was 3.3 months (range, 2.2 to 7.1 months). Responses occurred in six (40%) of 15 previously untreated patients and in six (50%) of 12 pretreated patients. Patients with a serum immunoglobulin M less than 40 g/L had a significantly higher response rate. The median time to progression for all patients was 16 months, and with a median follow-up of 15.7 months, nine of 12 responding patients remain free of progression. Treatment with rituximab was well tolerated, with approximately one fourth of patients experiencing some mild form of infusion-related toxicity, usually fever and chills. CONCLUSION: Our prospective data indicate that rituximab is well tolerated and active in patients with WM. Previously untreated and pretreated patients seem to benefit equally. Repeat 4-week courses of rituximab may prolong the duration of response of the disease, but this observation requires confirmation in prospective, randomized trials. Furthermore, studies that will combine rituximab with chemotherapy may be relevant.

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