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
Bibliographic record
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]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".