Waldenström's Macroglobulinemia: Long-Term Results with the M-2 Protocol

Abstract

Thirty-three patients with symptomatic Waldenström's macroglobulinemia have been treated with the M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Therapy was administered every 5 weeks for 2 years and every 10 weeks for an additional 1-3 years. Median clinical and laboratory parameters included age 70 years (range 52-87), performance status 1 (1-3), prior therapy 7, weight loss 12, symptomatic hyperviscosity 13, splenomegaly 22, lymphadenopathy 7, hemoglobin 9.6 g/dl (6.7-14.6), IgM paraprotein level 2000 mg% (340-11,600), and serum viscosity 2.1 (1.4-6.0). Responses were observed in 27 patients, of whom 21 were partial responses. Survival ranges from 1 to 120+ months with 58% of patients projected to be alive at 10 years. Twenty-one patients remain alive, of whom 10 are greater than or equal to 6 years from initiation of therapy with M-2. Treatment has been well tolerated with usually only mild to moderate hematologic toxicity. Median nadir white blood cells during the first cycle was 3000/mm3 (1000-5500). Peripheral neuropathy was seen in 54% secondary to vincristine. Nausea/vomiting, anemia requiring transfusions, and alopecia were each noted in approximately 25% of patients. Sepsis was observed in 2 patients. Two characteristics, age and prior therapy, were found to be of borderline statistical significance (p = 0.03) using univariate analysis but were not significant with multivariate analysis. The M-2 protocol may be able to produce prolonged survival in the majority of patients with Waldenström's macroglobulinemia. Additional trials are needed to develop recommendations for therapy as well as factors predictive for survival and suitability for treatment.

Waldenström's Macroglobulinemia

“…Vincristine, BCNU, melphalan, cyclophosphamide, and prednisone have also been used in the treatment of Waldenström's macroglobulinemia with a response rate of 81%. This response rate does not appear superior to that seen with the single alkylating agent chlorambucil [13].…”

Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003)

“…Several other therapeutic approaches have been used in patients with WM, including administration of another purine nucleoside analog, 2-CDA; alkylating agents, used either singly or in combination 23 ; steroids; ␣-interferon; anti-CD20 monoclonal antibody; and high-dose therapy. 9,10,12,16,[24][25][26] However, investigations of other therapies have the same limitations as previous studies of FAMP treatment, including the retrospective nature of several studies, small sample size, short follow-up periods, and possible patient selection and referral bias.…”

Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines

“…Combinations of alkylating agents with or without vinca alkaloids or anthracyclines have been used, 48,49 although no prospective randomized trial has compared these regimens to single-agent chlorambucil. Subsequent studies have evaluated the role of purine nucleoside analogues and found that this class of agents is effective in Waldenström macroglobulinemia.…”