Treatment of Waldenstrom's Macroglobulinemia with Rituximab: Prognostic Factors for Response and Progression

Abstract

Recent data have suggested that rituximab is an active agent for the treatment of Waldenstrom's macroglobulinemia (WM). However, the patients that are more likely to benefit have not been clearly defined. In order to address this question we evaluated 52 patients who were treated with single-agent rituximab in the context of prospective studies. Several clinical and laboratory variables were assessed for their correlation with response and time to progression. Twenty-three (44%) patients achieved a partial response after treatment with rituximab. Previously untreated and pretreated patients had the same probability for response. Higher response rates were noted in patients with serum monoclonal protein < 40 g/l, with serum albumin > or = 35 g/l and with kappa light chain. The median time to progression for all patients was 13.8 months. A multivariate analysis indicated that elevated serum monoclonal protein levels and low serum albumin were the dominant variables associated with shorter progression. Presence of two, one or none of these adverse prognostic factors was associated with time to progression of 3.6 months, 11 months and more than 40 months, respectively. We conclude that rituximab is an effective treatment modality for patients with WM. Patients with both low levels of monoclonal protein and normal albumin are the best candidates for treatment with standard dose rituximab.

Primary therapy of Waldenström macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN)

“…The major response rate (CR 1 VGPR 1 PR) was 68% (85% including >MR), which is higher than any of the drugs alone (>PR in 30% to 50% [3][4][5][6][7][15][16][17]27 ), indicating clinical synergism between bortezomib and rituximab. The median time to first response was 3 months, and compares favorably to rituximab alone (median time to response >6 months 3,4,6,7 ).…”

Comprehensive analysis of tumor microenvironment cytokines in Waldenstrom macroglobulinemia identifies CCL5 as a novel modulator of IL-6 activity

“…6 Current therapies for WM rely on the use of chemotherapeutic agents often in combination with the monoclonal antibody rituximab. [29][30][31] However, none of the currently available therapies provide a cure and although patients may initially respond to treatment, they perpetually relapse and most patients succumb to disease progression. It is therefore important to identify potential novel targets for the development of new therapies for WM patients.…”

Response rate to the treatment of Waldenström macroglobulinemia: A meta-analysis of the results of clinical trials

“…Seven (all Phase II) of the clinical trials (2,12,14,(26)(27)(28)(29), assessed the response to rituximab monotherapy. The combined RR for these trials was 44% (95%CI: 34-55, p<0.01).…”

“…Primary treatment options are mainly symptom-oriented (9) and include the use, alone or in combination, of alkylating agents (chlorambucil, cyclophosphamide, melphalan), nucleotide analogues (fludarabine, cladribine) or monoclonal antibodies (rituximab, interferon) (1, 2,[9][10][11][12][13]. In virtually all US patients, rituximab-based therapy is the first line treatment (14).…”