Up-to-date Information on
Waldenström’s macroglobulinemia

 

Overview of current trials

Learn more about the recent clinical trials and emerging therapeutic options for Waldenström’s macroglobulinemia.

Waldenström’s macroglobulinemia: clinical trials & studies

In this section you can learn more about the recent clinical trials in Waldenström’s macroglobulinemia, and the potential implications of emerging data for novel treatment strategies. The studies selected include those in at least phase II of development where targeted, chemotherapy-free agents are investigated. 

Ongoing studies and evolving treatments

  • Emerging treatment options include novel BTK inhibitors and B-cell lymphoma 2 (BCL2) inhibitors, for which a number of clinical trials are currently underway.1,2,3,4,5,6
  • Second-generation BTK inhibitors seek to improve bioavailability, increase kinase selectivity and have less off-target effects, with less cardiotoxicity and fewer AEs that may result in stopping treatment.7
  • Limiting off-target binding can potentially help reduce adverse events, as inadvertent binding to other kinases, including EGFR, HER4, and TEC, has been linked to side effects such as hypertension, rash, diarrhoea, and bleeding events.7
  • Gene expression and transcriptome studies have shown that BCL2 is highly expressed in WM cells, particularly in those patients with activating MYD88 mutations, making it an attractive therapeutic option.6

Requirementes for BTK selectivity - Waldenström's macroglobulinemia

Illustration: Requirements for BTK selectivity. Derived from Stephens DM, et al. Ther Adv Hematol. 2015; 6(5):242-252.8

Ongoing trials in patients with Waldenström’s macroglobulinemia

 

Phase III ibrutinib and zanubrutinib

 

Phase III ibrutinib

 

Phase II acalabrutinib

 

Phase II tirabrutinib

 

Phase II venetoclax

 

References

1.Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood 2020:136(18);2038-2050.
2.Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia. N Engl J Med. 2018: 378;2399-2410.
3.Buske, C, Tedeschi A, Trotman J, et al. Five-Year Follow-Up of Ibrutinib Plus Rituximab Vs Placebo Plus Rituximab for Waldenstrom’s Macroglobulinemia: Final Analysis From the Randomized Phase 3 iNNOVATETM Study. 62nd ASH Annual Meeting Exposition abstract.
4.Owen, RG, McCarthy, H, Rule, et al. Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study. Lancet Haemotology 2020: 7(2);E112-E121.
5.Sekiguchi N, Rai S, Munakata W, et al. A multicenter, open-label, phase II study of tirabrutinib (ONO/GS-4059) in patients with Waldenström’s macroglobulinemia. Cancer Sci 2020:111(9);3327-3337.
6.Castillo J, Allan J and Siddiqui T. Multicenter Prospective Phase II Study of Venetoclax in Patients with Previously Treated Waldenstrom Macroglobulinemia. Clinical Lymphoma, Myeloma and Leukemia 2019: 19(10);Supp E39-E40
7.Tam C, Grigg AP, Opat S, et al. The BTK inhibitor, BGB-3111, is safe, tolerable, and highly active in patients with relapsed/refractory B-cell malignancies: initial report of a phase 1 first-in-human trial. Blood 2015: 126;832.
8.Stephens DM, Spurgeon SE. Ibrutinib in mantle cell lymphoma patients: glass half full? Evidence and opinion. Ther Adv Hematol 2015: 6(5);242-252.
9.Dimopoulos M, Sanz RG, Lee H, et al. Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial. Blood Adv 2020: 4(23);6009–6018.