Irene Ghobrial, MD of the Dana-Farber Cancer Institute, Boston, discusses the advances made in the treatment of Waldenström’s macroglobulinemia and the subsequent clonal evolution that can occur post-therapy. The mutations that cause Waldenstrom can vary from patient to patient and they include MYD88 and CXCR4. This means that the biology of each patient is different, consequently affecting their treatment options. As well as mutations, 20% of patients have familial Waldenström’s. Familial Waldenström’s is still novel and any information regarding germline mutations and germline sequencing is rudimentary. However, there is potential for it to lead to the screening for monoclonal gammopathy of undetermined significance (MGUS) and smoldering Waldenström’s in patients, allowing physicians to predict individuals that are more susceptible to develop it. Post-therapy, it is important to continue to monitor patients, because treatment with multiple therapies like proteasome inhibitors, alkylators, rituxan (rituximab) and ibrutinib, can lead to resistance and clonal evolution. It is crucial to know which mutations lead to clonal progression so that they can be targeted for prevention, and it has been suggested that the CXCR4 mutation may be the driver in Waldenström’s. Recorded at the 2017 annual meeting of the European Society for Blood and Marrow Transplantation.