Emerging drugs for the treatment of Waldenström macroglobulinemia
- 21 September 2020
- journal article
- review article
- Published by Taylor & Francis Ltd in Emerging Drugs
- Vol. 25 (4), 433-444
- https://doi.org/10.1080/14728214.2020.1822816
Abstract
Waldenström’s Macroglobulinemia (WM) is an indolent lymphoma with uniquely distinct and heterogenous clinical and genomic profiles. Clonal lymphoplasmacytic cells secrete monoclonal IgM. More than 90% of patients harbor a mutation in MYD88 gene, leading to the constitutive activation of downstream pathways, involving BTK-mediated signaling. The use of BTK inhibitors has changed the treatment landscape of WM and has paved the way for new approaches to therapy. WM is an orphan disease and ibrutinib is the only FDA/EMA approved agent. Currently established agent combinations will be reviewed with a focus on emerging therapeutic options. These include second generation inhibitors, agents that target other molecules in the BCR signaling pathway, CXCR4 inhibitors, proteasome inhibitors and anti-CD38 antibodies. The current research goal is to establish a combination that can induce deep and durable responses with minimal associated toxicity. In addition, agents that can overcome ibrutinib resistance or act in a synergistic manner with BTKi are under investigation. The optimal therapeutic approach for WM patients is not currently established. The question of whether a combinatory (or synergistic) regimen to overcome resistance and allow for fixed- duration treatment will allow for deep/durable responses is being addressed in ongoing clinical trials.Keywords
This publication has 90 references indexed in Scilit:
- Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemiaHaematologica, 2012
- Progression in smoldering Waldenström macroglobulinemia: long-term resultsBlood, 2012
- Helical assembly in the MyD88–IRAK4–IRAK2 complex in TLR/IL-1R signallingNature, 2010
- Phase II Trial of Weekly Bortezomib in Combination With Rituximab in Relapsed or Relapsed and Refractory Waldenström MacroglobulinemiaJournal of Clinical Oncology, 2010
- Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180Journal of Clinical Oncology, 2009
- Long-term outcomes to fludarabine and rituximab in Waldenström macroglobulinemiaBlood, 2009
- Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group–directed intergroup trial S9003Blood, 2009
- Thalidomide and rituximab in Waldenstrom macroglobulinemiaBlood, 2008
- Targeting NF-κB in Waldenstrom macroglobulinemiaBlood, 2008
- Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's MacroglobulinemiaSeminars in Oncology, 2003