ASH 2021 Day 1: From Iceland to Bispecifics

ASH 2021 Day 1: From Iceland to Bispecifics

by | Dec 11, 2021 | Jack Aiello

Dec 11, 2021 – The day began at 3:30 a.m. PST for the privilege of being able to attend the International Myeloma Working Group (IMWG) meeting. The IMWG has over 250 myeloma specialists who meet twice a year. The agenda included a review of current projects and a discussion of possible proposals to specifically produce guidelines for myeloma treatment. For example, in 2021, guidelines were produced for redefining plasma cell leukemia as 5% circulating plasma cell, infection prevention (very timely during this pandemic), bone disease, and the role of mass spectrometry. Ongoing projects include the management of renal failure, CAR T, and smoldering multiple myeloma (SMM) guidelines.  

Then it was off to “virtually” attend a number of first-day oral abstract presentations.  The format of these 15-minute talks is for the primary investigator to present their slides for 10 minutes and allow 5 minutes for questions. The hybrid nature of this year’s ASH — where facilitators, presenters, and the audience is a blend of in-person and virtual— made this quite a challenge. This format worked better as the day went on but did cause some information to be missed, if you attended virtually.  [On the other hand, it snowed in Atlanta 2 years ago and I missed some information while being there in-person.] 

These are my highlights from today’s presentations: [Abstract#] 

Iceland 

There were at least 3 studies presented from the iStopMM project, which is in its 5th year. If you’re not familiar with this project and its potential importance, check out Dr. Brian G.M. Durie’s recent blog video.  

One essential question asked was whether or not we should screen for monoclonal gammopathy of undetermined significance (MGUS). Other diseases offer early screening, resulting in the improvement of overall survival so why shouldn’t this be true for MGUS, a possible precursor to myeloma? Over 75,000 individuals were screened with nearly 4,000 MGUS patients found and after 3 years of follow-up some have become SMM and myeloma patients. [156] 

While this is a long-term study, several interesting outcomes have already been determined: 1) SMM occurs in 0.5% in persons 40 years or older but according to today’s risk stratification, only 1/3 of these SMM patients are considered intermediate or high risk; [151] 2) There is no relationship between MGUS and the susceptibility of either getting COVID-19 or the severity of it. [154] 

Bispecific Antibodies 

There were several updates provided on bispecific antibodies with more to come on Sunday and Monday.  The Bispecifics often use 1-2 “step-up” doses (start with lower amounts) to mitigate potential cytokine release syndrome (CRS). Today, abstracts provided results for:

1) Cevostamab (FcRH5 marker on the MM cell x CD3 on the T cell) given every 3 weeks to n=161 patients (pts) heavily pre-treated (including prior BCMA) resulted in ORR of 57% and mDOR of 11.5 mos for dosing 132-198mg via IV; [157]

2) Talquetamab (GPRC5D x CD3) given SubQ to N=55 pts resulted in ORR 67-70%; [158]

3) And when talquetamab is combined with dara N=21 showed an ORR 77-85% (no dara within prior 90 days); [161] 

4) REGN5458 (BCMAxCD3) N=73 provided ORR = 75% at the combined 200-800mg dose levels. [160] 

Other Studies 

  1. An update with a 2-year follow-up was provided for the Griffin study: [Dara]RVd -> SCT -> [D]RVd -> [D]R maintenance (2 yr). Dara arm results in superior outcomes after 2-year follow-up: MRD- (10-5) 64% vs 30%, CR 82% vs 61%, and MRD- >12 mos durability 44% vs 13%. [79] 
  1. Iberdomide (a CELMod) + dex demonstrates efficacy in triple-refractory patients, including those 100% refractory to IMIDs, ORR 26% N=26 and pts with previous BCMA, ORR 25% N=24. [162] 
  1. The PROMISE study examines potentially high-risk individuals, specifically Black/AA (N=2439) and those with first degree relative dx with hema malignancy or precursor to MM (N=3866). MGUS screening via both SPEP (6%) and Mass Spec (13%) confirmed both higher rates and increased sensitivity with Mass Spec. [153]  

That’s it for tonight.  While my first meeting tomorrow isn’t until 6:30 a.m. PST, one benefit of a virtual ASH is that many sessions are recorded and available for replay (just in case I oversleep).   

Be your own best patient advocate. 

Jack Aiello, on Twitter @JackMAiello 

Symposiums Promise Many New Lily Pads

Symposiums Promise Many New Lily Pads

by | Dec 11, 2021 | Linda Huguelet

Today was filled with educational symposiums that offered medical professionals attending the 63rd American Society of Hematology (ASH) conference the opportunity to earn continuing education credits. 

For me, it provided a glimpse of what is to come this weekend and it reconfirmed that there are many more treatment lily pads that I can leap to in the future. Thanks to the International Myeloma Foundation (IMF) and our generous sponsors, this is my 9th year attending this conference. 

Every year offers great insight into the amazing research that is ongoing to find a cure for multiple myeloma. But some years, I feel like there are more leaps than others. I think 2021 will be one of those years pushing future treatment options to the next level. Bispecific antibodies and CAR T-cell therapies have been featured at previous ASH conferences, but the number of options is reaching a new level and new targets being studied provide more ways to outsmart our continually changing myeloma. 

With all this advancement comes more choices — another reason to be an informed patient. There will be a greater need to understand the sequence of treatments. For example, can you take a bispecific antibody before having CAR T-cell therapy if they target the same antigen on the myeloma cell? Recently approved new therapies and several on the verge of approval target BCMA. So, this is a question that will be widely discussed this weekend. And there is literally an alphabet soup of new targets being explored, so the options and combinations continue to explode. 

Saturday began at 6:30 a.m. (3:30 a.m. for our team members from the West Coast) with the International Myeloma Working Group (IMWG) meeting and was followed by a day filled with abstracts on all these amazing studies. 

Stay tuned to all the information our team will be sharing with you over the next few days. 

Linda Huguelet, Chattanooga Multiple Myeloma Networking Group 

Linda Huguelet, on Twitter: @LindaMYELOMA