End of the Line: The IMF’s Best of ASH!

End of the Line: The IMF’s Best of ASH!

Before ASH even started, there were many educational Satellite Symposiums taking place.  The IMF’s program is CME-certified and available online (Adapting Clinical Practice to a Rapidly Changing Therapeutic Landscape in Multiple Myeloma).  This program is one bookend of ASH, with the other being the IMF’s Best of ASH annual webinar.

This year, the IMF held the usual Best of ASH for everyone to register for free and participate in —with a live Q&A with IMF Chairman of the Board Dr. Brian G.M. Durie. Additionally, the IMF Support Group Leaders had a special Zoom room gathering where all the leaders were invited to join and watch the webinar and have an additional Q&A with Dr. Durie.  

Questions ranged from discussion on novel agents and how they are changing treatment for high-risk patients, smoldering multiple myeloma (SMM) and high-risk smoldering multiple myeloma (HRSMM) trials, newly diagnosed multiple myeloma (NDMM) patients and 4 drugs upfront (use the best treatment option available at each stage) and of course, CAR T and bispecifics in relapsed/refractory multiple myeloma (RRMM) and potentially upfront for even better responses.

Dr. Durie presented the highlights from ASH, including six iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) ASH Abstracts, consisting of 4 oral presentations and 2 posters. I’m excited for all the results from this important research, and I am looking forward to additional updates instead of using serum protein electrophoresis (SPEP), or mass spectrometry to measure the myeloma protein as it is so much more sensitive and showing deeper levels of minimal residual disease (MRD) negativity, even at the 10-5 and 10-6!  

I look forward to how this will be interpreted for treatment decisions in the real world.  Another focus I’m watching for is information on DNA genetic sequencing to help determine genetic features that predispose to monoclonal gammopathy of undetermined significance (MGUS) and progression to myeloma. 

When we had the opportunity to be in Iceland to listen to iStopMM updates in 2018 and 2019, the iStopMM team shared insights into the tree; there were a couple that stood out to me:

  • Flow Cytometry – The iStopMM study is employing Next Generation Flow (NGF) cytometry in the care of individuals with MGUS and those who are diagnosed with SMM and MM.  The aim is to be able to use this emerging technology to identify those who will progress to active disease so that their follow-up and treatment can be tailored to them in the future. NGF also gives insights into tumor microenvironment, the cells around the myeloma cells that nurture and support them.  Learning more about this crucial part of myeloma development might open the door to new ways of treating or preventing myeloma in the future.
  • Psychological impact of cancer screening – A part of the iStopMM project is to do deep analysis into the psychological effects of screening for MGUS and how knowing about precursor conditions (that, in most cases, is otherwise harmless) will affect mental health. This information is highly relevant for other cancer screening programs as well.
  • COVID-19 – The iStopMM team just published a paper using iStopMM data and “created a new branch of the tree” to answer pressing questions for individuals with MGUS —there is no increased COVID-19 severity with MGUS (Abstract #154)

On last night’s Q&A with Dr. Durie and leaders, Dr. Durie stated that Iceland may be a place where we can either prevent or even cure myeloma!  Thanks to all the Icelanders for participating in the iStopMM trials!

Of course, we all continue to be excited about CAR T therapy, and as Jack Aiello stated in his blog, “Which CAR to Hitch a Ride with?”  Well, CARTITUDE-1 (cilta-cel) continues to impress with excellent Overall Response Rate (ORR) of 97.9% and even more encouraging is the stringent Complete Response (sCR) Median 1-year follow up:  67 and actually deepened over time; Median 2-year follow up 83! (Abstract #549)  Remember, these are patients that have been heavily pre-treated.  Imagine what the results may be if used upfront in NDMM?

As #ASH21 comes to a close, the research continues on.  So, keep on keepin’ on and look to the future with hope and share that hope with others. We’re all in this together.

Thanks to the IMF for being the first to bring myeloma patients/support group leaders to ASH.  It’s an honor and privilege to be a part of the Team.  Thanks to all the sponsors for supporting this valuable opportunity:  BMS, Karyopharm, and Takeda Oncology.

My last song to share with you from #IMFASH21 is “End of the Line” by The Traveling Wilburys.  

Fun fact: The name “Wilbury” was conceived in 1987 while Jeff Lynne was producing George Harrison’s “Cloud Nine” album.  Whenever there was a mistake, Harrison would tell Lynne, “That’s okay, WE’LL just BURY it in the mix …” 

Michael Tuohy, on Twitter: @IMFmikeMYELOMA 

Day 1: A Long but Inspiring and Encouraging Day

Day 1: A Long but Inspiring and Encouraging Day

The first official day of ASH activities started at 6:30 a.m. with the International Myeloma Working Group (IMWG) Breakfast Meeting. The IMWG is exactly that — a working group of myeloma experts from across the world, who come together periodically to investigate and create new guidelines for everything myeloma. They form different subgroups to review, collaborate, and make recommendations for new, up-to-date guidelines on many topics.   

What a blessing it is to be in a room with this much talent and passion for myeloma! I feel very honored to have been given this opportunity to experience such collaboration and cooperation between experts for the good of myeloma patients all over the world.  

Now, on to the oral presentations. Some highlights from Day 1 include: 

  • Exciting information coming from the most recent update of the Griffin Study. This study is looking at Dara plus RVd in patients with ASCT eligible Newly Diagnosed MM and updated analysis includes subjects after 24 months maintenance treatment. It appears that the quad therapy yielded 81% MRD negative subjects vs the 44% with only the triplet VRd therapy. We know that sustained MRD Negativity is more important than one snapshot, but so far, 6-month and 12-month MRD negativity remain improved with quad therapy. Will this study further direct quad therapy as SOC in induction therapy and then dual therapy in the maintenance phase?  
  • Also, final analysis of the BELLINI study supports a biomarker-driven approach in the current Venetoclax development program in t (11;14) RRMM. Consistent results from this study are showing improvement in PFS and OS in patients with t (11;14) or BCL2 high expression. 
  • Liquid biopsies are gaining strength in research! Will checking circulating plasma cells in initial workups of patients and monitoring throughout disease management be the new standard, rather than serial bone marrow biopsies?  
  • For many studies, one of the AIMS is to eliminate dexamethasone from the commonly used regimens. This is good news when it comes to quality of life for myeloma patients. In the future, we may be able to remove this drug that, while effective, causes many patients so many side effects that affect quality of life.  
  • Bispecific antibodies are up and coming! Different targets are being researched including BCMA and GPRC5D, among others. Promising data from Phase I studies, doses are being escalated and safety profiles are being identified.  
  • iStopMM is a screening that is an unbelievably HUGE undertaking, giving endless amounts of data and assuredly, for years to come! Symptomatic screening for MGUS hasn’t been studied before, and the study’s aim states to determine if early detection can lead to the possibility of cure. Less than 2-6% of myeloma patients are diagnosed at precursor states. So how can we find them early? This Icelandic study had around 150,000 subjects show interest, with about 75,000 screened in the study. Of this group, 3,725 patients were found to have MGUS. Then this group blindly randomized into 3 arms: Arm 1 (current standard of care), Arm 2 (current IMWG guidelines), and then Arm 3 (more intensive follow-up). Initial findings are promising, but no recommendations are to be made until further research continues. Additional study looked into MGUS and COVID-19. Of 72,000 eligible subjects, 32,000 were tested. Results show that MGUS does NOT increase risk of contracting COVID, nor does it make the effects of the virus more severe, if infected. GOOD NEWS! Ideas for future research on this study population include evidence of chronic allergies/auto immune diseases/familial linkage —an important and expansive research! 
  • Reports given for dose expansion phase of iberdomide — a novel IMiD therapy, like Rev/Pom, but big differences exist. Iberdomide is tumoricidal, while Rev/Pom are not. Also, side effect profiles are completely different, as iberdomide appears to be more easily tolerated, with typical IMiD-related events like GI effects, rash, and fatigue not noted. This is exciting news, again, for quality of life!  

Final thoughts of the day: new and upcoming promising therapies are simply not cost-efficient or accessible for most patients. How do we improve access to these new therapies that can offer so much hope? For some patients that do not have access to large academic centers with myeloma specialists actively involved in their care, will these therapies remain unreachable to them? How do we bridge the gap? Food for thought!  

Also, I am grateful that so many studies have a focus of improving quality of life for patients. This should ALWAYS be the AIM. Some thoughts from an oncology nurse, who is passionate about myeloma and from our 10-month-old, 110-lb. Newfoundland puppy, Bean, who just wants to have some attention today. 

Becky Bosley, on Twitter @MidAtlanticMSG