de Tute, Ruth;
Counsell, Nicholas;
Clifton-Hadley, Laura;
D'Sa, Shirley;
Pratt, Guy;
Campbell, Gavin;
Campbell, Lauren;
... Auer, Rebecca; + view all
(2024)
Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia.
Leukemia
10.1038/s41375-024-02162-5.
![[thumbnail of Counsell_Long-Term_outcomes_R2W_resubmit_clean_nc.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/text.png) |
Text
Counsell_Long-Term_outcomes_R2W_resubmit_clean_nc.pdf Access restricted to UCL open access staff until 27 August 2024. Download (430kB) |
Abstract
There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrőm macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response. Sixty treatment-naïve WM patients were enroled into this phase II trial and randomised (2:1) to receive cyclophosphamide and rituximab with either bortezomib (BRC) or fludarabine (FCR). The primary objective was to assess the overall response rate (ORR) in eligible patients receiving BRC (N = 41). An ORR of 97.6% (95%CI:87.1–99.9) was observed; 27 (65.9%) patients remain alive without progression after 62.6 months median follow-up, with 2-, 3- and 5-year progression-free survival (PFS) rates of 92.7% (95%CI:79.0–97.6), 80.5% (95%CI:64.8–89.7) and 65.5% (95%CI:48.8–77.9). Persistent WM B-cells were demonstrable in 19/38 patients at the end of treatment (median 0.24%, range 0.02–11.2%). PFS was markedly longer in patients with BM B-cell depletion (<0.004%) compared to those who had persistent BM B-cells detectable at end of treatment (HR = 0.06, 95%CI:0.01–0.47, p < 0.001), and remained independently associated after adjusting for baseline risk stratification or investigator-assessed response. BRC is a tolerable, highly efficacious regimen for treatment-naïve WM patients. BM B-cell depletion is independently associated with patient outcomes.
Archive Staff Only
 |
View Item |
