- Combination treatment with ixazomib citrate, rituximab, and dexamethasone is feasible, shows promising efficacy, and manageable toxicity in patients with relapsed or progressive Waldenstrom’s macroglobulinemia.
Why this matters
- Proteasome inhibitors like bortezomib have shown considerable efficacy in treating progressive Waldenstrom’s macroglobulinemia, but polyneuropathy is a common problem.
- Adding dexamethasone with alternative proteosome inhibibitor ixazomib may be effective.
- A multicenter phase 1/2 trial of 60 patients with relapsed Waldenstrom’s macroglobulinemia, treated with ixazomib, rituximab, and dexamethasone (IRD).
- Patients received 4 mg oral ixazomib citrate and 20 mg dexamethasone every week on a 28-day cycle.
- Rituximab was added in cycle 3.
- Phase 2 primary endpoint: overall response rate after 8 induction cycles.
- Funding: Takeda Oncology; Roche; and the Dutch Cancer Society.
- Phase 1: ixazomib 4 mg was feasible and continued as phase 2 dose.
- Phase 2: 50 patients were included.
- 39 patients completed 8 cycles of induction therapy.
- 11 patients discontinued treatment due to progression (n=5), toxicity (n=3), intercurrent death (n=2), or insufficient clinical benefit (n=1).
- 74% of patients achieved the primary endpoint (≥very good partial response [VGPR], 16%; ≥partial response [PR], 52%; at least minimal response [MR], 74%).
- Best overall response rate was 88% (complete response, 2%; VGPR, 22%; PR, 44%; MR, 20%).
- Median follow-up was 19.5 (range, 7-49) months.
- Median duration of response and median PFS were not reached.
- IgM levels decreased significantly from 3.93 to 2.37 g/dL by cycle 2 (P<.001>
- 15 patients experienced a total of 21 serious adverse events.
- 6 patients died due to:
- progressive disease, 2;
- progressive multifocal leukoencephalopathy, 1 (symptoms present already at entry);
- unrelated deaths in elderly patients with multiple preexisting comorbidities, 2; and
- graft vs host disease after progression and subsequent allogeneic stem cell transplantation, 1.