Bortezomib is active in Waldenstrom’s Macroglobulinemia (WM)—Results of a National Cancer Institute of Canada (NCIC) phase II study in previously untreated or treated WM
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abstract
7543 Background: WM is a B cell lymphoma characterized by a serum monoclonal IgM and marrow infiltration by lymphoplasmacytoid cells. Bortezomib is a proteasome inhibitor active in myeloma and other hematologic malignancies. In this 2-stage study, 27 WM pts received single agent bortezomib with RR as primary endpoint. Methods: Eligibility: symptomatic WM (Hb <110 g/L; lymphadenopathy; organomegaly; or hyperviscosity); ≤2 prior chemo regimens (± rituximab). Bortezomib 1.3 mg/m2 IV given d1, 4, 8, 11 on a 21d cycle until PD or 2 cycles beyond CR/SD. Nodal disease was included in response criteria (2nd International WM Workshop). Results: Median age 65 (46–87), M:F 14:13, no prior therapy 11 (44%). At entry, median IgM 38 g/L (11.2–83.3); median Hb 108 g/L (63–142); 18 (66%) with nodal disease on CT. At a median of 6 cycles (2–35), 11/27 (41%) patients had ≥50% decrease in IgM alone plus 10 (37%) minor responses (25–49% decrease). Using IgM + nodal criteria: 1 CR, 5 PR (≥50% decrease in IgM and bidimensional disease), 20 SD, 1 PD = overall RR 22% (95% CI 8.6–42.2%). IgM responses were prompt (median 2 cycles; range 1–8) with nodal responses lagging (median 4 cycles). Hb increased by ≥10g/L in 18 pts (66%). Bortezomib was well-tolerated with most non-hematologic toxicities Gr 1–2: fatigue (74%), nausea (63%), myalgias (51%), non-neutropenic infections (48%), diarrhea (44%), constipation (44%). 18 pts (66%) developed neuropathy (sensory): typical onset 2–4 cycles; Gr 3 in 5 pts; 15/18 (83%) improving ≥1 grade (11 complete) in 2–13 mo. Gr 3 myalgias in 2 pts resolved in <1 mo. Gr 3–4 thrombocytopenia (30%) and neutropenia (18%) led to 12 missed doses, 1 dose reduction. Conclusions: Bortezomib is active in WM with 78% pts with ≥25% fall in IgM, 41% with IgM response criteria of ≥50% decrease, 22% with composite nodal/IgM responses. Despite prompt IgM and hematologic improvement, decrease in nodal disease is slow, reflected in overall responses lower than IgM alone. Although bortezomib is generally well-tolerated, neuropathy is common but reversible. Bortezomib combinations with conventional cytotoxic or targeted agents warrant further study in WM. This is a NCIC CTG study with a grant from NCIC and funds from Canadian Cancer Society. [Table: see text]
