From the science desk, a report on:

  • The 12th International Workshop on Waldenström’s Macroglobulinemia (IWWM-12) that took place in Prague, Czech Republic from October 17-19, 2024 where leading experts gathered to discuss the latest advances in the understanding and treatment of WM, and
  • The 66th annual meeting and exposition of the American Society of Hematology (ASH) that took place in San Diego, California from December 7-10, 2024.

The WMFC reviewed all of the IWWM-12 abstracts submitted in Prague and found that very many of the presentations/posters simply confirmed the work of others.  For example, several abstracts confirmed three WM lineages: B memory cell-like, plasma cell-like, and mixed lineage.  Readers may recall that the WMFC funded Dr. Zachary Hunter’s original work in this field a few years ago.  Furthermore, other abstracts described tweaks to very old treatments or added Bortezomib to older treatments.  (Note: Practitioners often avoid treating WM with Bortezomib because it may aggravate neuropathies.)

Here are highlights from the Prague IWWM-12 we found noteworthy:

  • Dr. Shirley D’Sa, a well-known London, England-based WM specialist whom you may know from our recent National Zoom discussion of Bing-Neel and Neuropathy, reported on the high efficacy of Zanubrutinib in treating Bing-Neel syndrome.  Several other, less detailed papers, also reported on this topic.
  • MB-105, a CD20 CAR-T product, is being tested in Seattle.  Three out of 10 initial patients have achieved a complete response (CR) that may be curative but it is much too soon to confirm this result.
  • Loposofine I-131 has shown good but not stellar responses.  This combination of a radioactive isotope conjugated to an antibody was tried two decades ago under the name Bexxar and was pulled from the market because of poor demand.  Additionally,  the drug produced high rates of transformation to myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) that did nothing to create demand.
  • Dr. Neil Berinstein of SunnyBrook Hospital in Toronto presented his initial BRAWM trial results where participants are being treated with Bendamustine plus Rituximab and Acalibrutinib.  To date, more than half the participants are achieving a Very Good Partial Response (VGPR) that represents a 90% reduction in serum IgM level from baseline and complete resolution of enlarged lymph nodes and enlarged spleen.  A China-based trial has reported roughly similar results using B&R plus Zanubrutnib.
  • Currently, researchers consider Pirtobrutinib to be the best non-covalent BTK (Bruton’s Tyrosine Kinase Inhibitor) but a novel variant, Orelabrutinib,may prove to have an edge.  We await further data.
  • Beigene’s BTK degrader BgB-16673 appears to produce results equivalent to those of BTK inhibitors.  Similarly, Beigene’s BCL-2 inhibitor Sonrotoclax is performing well in trials.
  • A trial of Loncastuximab at the Bing Center for Waldenström’s Macroglobulinemia at Dana-Farber Cancer Institute shows definite signs of promise.

And here is the report on abstracts from the ASH Conference:

  • Approximately 40 abstracts deal specifically with WM and 89 mention WM.
  • As many of the abstracts had just recently been presented at IWWM-12 in Prague, there was not much new.  Interestingly, the BRAWM trial did not submit an abstract to ASH.
  • Unlike the laborious system of locating abstracts from IWWM-12, the ASH system for locating abstracts is easily skimmed.  The link (also above) is repeated here.
  • Readers may be interested, in particular, to read Dr. Zach Hunter’s abstract “Analysis of Alternative Splicing in Waldenström’s Macroglobulinemia Reveals Novel Targets, Insights into IgM Production and Improved Gene Level Expression Estimates” to be found at this link.