ASH 2021: My Saturday Highlights 

ASH 2021: My Saturday Highlights 

Saturday at #ASH21 was a full day that began at 6:30 a.m. ET, with the #IMFASH21 team being invited to be a “Fly on the Wall” at the International Myeloma Working Group’s (IMWG) breakfast meeting. This prestigious group of over 250 global myeloma specialists meets twice a year to collaborate on projects. They form working groups, give updated status reports, produce guidelines for myeloma treatment, and decide upon new projects. At ASH, they also discuss and preview some ASH abstracts (which are embargoed until they are officially presented at ASH.)    

I am both grateful and in awe at the amount of work this group does — and I mean “group.” As Susie Durie often would say: “Their egos are checked at the door,” and they come together on behalf of helping the entire myeloma community — from the general oncologists who don’t have time to come to ASH, to the patients and caregivers trying to keep up with the rapidly changing treatment paradigm. Learn more about IMWG and its guidelines/publications here.   

After leaders attended the IMWG breakfast, we went directly into our schedule to view oral abstracts virtually. However, to our frustration, there were technical glitches, and we were not able to view some of the morning abstracts. But as resilient leaders, we will look to the replays. Our virtual badges give us the ability to watch #ASH21 replays until January 1.    

I mentioned in my pre-ASH blog that I would be reporting a bit on the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) project in each of my blogs. iStopMM aims to map the epidemiological and clinical characteristics of smoldering multiple myeloma (SMM) in the general population based on a large population-based screening study.    

Michael and I have been extremely interested in this project since its inception 5 years ago. This year at ASH, the iStopMM team has four oral abstracts and two posters — quite an amazing accomplishment! I listened with great anticipation, and I continue to be inspired by the results and the selflessness of the Icelandic people in their willingness to volunteer and to participate in this research! Read more in Oral Abstract 151: Prevalence of SMM: Results from iStopMM study Sigrun Thorsteinsdottir MD, Ph.D

Additionally, refer to oral Abstract 154 on monoclonal gammopathy of undetermined significance (MGUS) and COVID-19 presented by Sæmundur Rögnvaldsson, MD (University of Iceland – Reykjavík, Iceland). This, of course, is of particular interest as we all learn how COVID-19 affects us. For MGUS patients in this large population-based study that included 75,422 individuals screened for MGUS, they did NOT find MGUS to be associated with SARS-CoV-2 susceptibility or COVID-19 severity. This is contrary to multiple myeloma (which is preceded by MGUS). These findings suggest that immunosuppression in MGUS differs significantly from that of multiple myeloma and is important since they can provide information for management as well as recommendations for individuals with MGUS. 

For those with relapsed/refractory multiple myeloma (RRMM), Abstract 162 Iberdomide (IBER) in combo with dexamethasone (DEX) in patients with RRMM: Results from the Dose Expansion Phase of the CC-220-MM-001 Trial (Sagar Lonial)   

Patients were heavily pretreated with 97% triple-class refractory. For me, this was an abstract I had been looking forward to, as it is a new mechanism of action. Cereblon E3 ligase modulator  

(CELMoD) is “easy” since it’s all oral. Something to share with my support group members at home that is RRMM. 

Saturday was packed with excellent presentations that continue to give us hope and are getting us closer to a cure, with lots of updates on MGUS, SMM, MM, and RRMM. Please read all the other excellent blogs from the #IMFASH21 Team members. Sharing the Hope!  

Thanks to all the dedicated researchers. Cheers to your continued hard work that our futures will benefit from!   

Robin Tuohy, on Twitter @IMFsupport  

The Day of Symposiums

The Day of Symposiums

Hybrid Meeting Format  

As with previous years, the International Myeloma Foundation (IMF) held its signature satellite symposium during that 63rd annual meeting of the American Society of Hematology (ASH). It featured Drs. Brian G.M. Durie (IMF Chairman of the Board), S. Vincent Rajkumar (Mayo Clinic — Rochester, MN), Tom Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA), Jesus San-Miguel (Clinica Universidad de Navarra — Navarra, Spain), Philippe Moreau (University Hospital — Nantes, France). Absent this year was Dr. Shaji Kumar (Mayo Clinic — Rochester, MN).   

The symposium flow included a hypothetical case presentation, followed by how you treat questions and audience vote, the speakers’ case for why they voted the way they voted, and then audience polling to see if the speakers changed any audience minds.   

The case studies and presentations ranged from smoldering myeloma to relapsed/refractory myeloma, approved drugs, drug combinations, and drugs in the pipeline.   

I noted on the disclosure slides the only one that did not have ANY disclosures was Dr. S. Vincent Rajkumar. Does it mean the others are conflicted, and you should consider their discussions to be biased? Well, NO! I invite you to read this Twitter thread to see why not.   

The significant benefit of treating high-risk SMM patients in myeloma is high, noted Dr. San-Miguel, up to 7 years of progression-free survival (PFS) before the smoldering myeloma progressed to full-blown myeloma. Not only was the progression delayed, but the risk profile post-progression was similar to those on the wait-and-watch approach. Dr. Rajkumar indicated the wait-and-watch experiment has failed for high-risk smoldering myeloma patients.    

The speakers noted the features that made SMM high risk (seen below), where the presence of these features indicated an up to 50% chance of progressing to myeloma in two years.    

Factors Identifying 50% Risk of Progression at 2 Years 

Over the last two years, the researchers consider high-risk indicators have evolved. You may have heard the 2/20/20 model. They are now indicating the potential for the model to evolve to a 2/20/0.02% model allowing for frequent monitoring of the SMM patient and early warning system that the smoldering myeloma will progress to full-blown myeloma. Watch the studies in this area as research has indicated the importance of early intervention pre CRAB.    

Circulating Tumor Cells Predict Risk of Progress in SMM Patients 

Some exciting questions are being asked: Can CAR T replace upfront high-dose autologous stem cell transplant (ASCT)? Dr. Morreau indicated that a clinical trial is in the design phase in Europe.   

Dr. Martin’s wish list for future bispecific antibodies in relapsed/refractory myeloma included outpatient dosing with low cytokine release syndrome (CRS) and neurological toxicity, convenient administration (every 4, 6, 8 weeks). Dr. Martin had a similar wish list for BCMA CAR T cells, including faster manufacturing, better expansion, dual targeting, and outpatient administration.    

One of the highlights of the symposium was that all the bispecific antibodies for relapsed/refractory myeloma have a single drug overall response rate (ORR) of over 50%, some even 80%. This high ORR was unheard of in the chemotherapy era and even in the age of novel drugs such as Velcade® (bortezomib), Revlimid® (lenalidomide), Kyprolis® (carfilzomib), or Darzalex® (daratumumab).   

Summary of Bispecific Antibodies in RRMM 

Dr. Durie discussed the unmet need of triple-class refractory myeloma patients. Those patients, despite all efforts, their myeloma continue to progress and eventually die. He indicated the issue is even more exasperated with the withdrawal of melflufen and panobinostat from the market, and the limited use of venetoclax. 

The Unmet Needs of Triple Refractor Myeloma Patients 

And finally, Dr. S. Vincent Rajkumar of the Mayo Clinic unveiled his “Treatment Algorithm for 2020”. This algorithm embraces the principle of triplet preference, including at least two new drugs (not sure just drugs or if feasible drug classes), consideration of transplant in patients eligible for transplant. He said, “My preference is for people not to use this algorithm and urge patients to sign up to clinical trials.”   

During this symposium, I heard the phrases   

  • Flattening of the curve (the survival curve)   
  • Long treatment-free interval (drug holidays)  
  • Ease of administration (at home and subcutaneous administration, treatment intervals of >2 weeks)  
  • Fewer side effects   

There was an acknowledgment by the group that more needs to be done to bridge the gap between what the on-the-ground country by country reality is and the potential these new drugs offer.   

The IMF teams will be busy at ASH and will be facilitating either virtual or hybrid meetings:   

Yelak  

Sharing The Hope!  

Yelak Biru, on Twitter: @NorthTxMSG  

With a goal of CURE

With a goal of CURE

“The difference between the impossible and the possible lies in a man’s determination.”
-Tommy Lasorda

The International Myeloma Foundation’s International Myeloma Working Group (IMWG) Symposium included case discussions that highlighted emerging topics in multiple myeloma. Dr. Jesus San Miguel (Clinica Universidad de Navarra – Navarra, Spain) presented the first case. His presentation involved The treatment of high-risk smoldering multiple myeloma (HRSMM). During his presentation, he convinced the audience that the CESAR study was the most agreed-upon therapy of those that were offered. This was done after he polled the attendees before and after his presentation.

The initial pre-presentation poll completed by the audience wasn’t unanimous regarding the various therapies for HRSMM. After presenting the CESAR trial data, the post-presentation poll completed by the audience overwhelmingly favored the recommended treatment to achieve a cure of myeloma.

The CESAR trial is a Spanish study that involves Kyprolis® (carfilzomib)+ Revlimid® (lenalidomide) + dexamethasone (KRd). The drug regimen is followed by a stem cell transplant and subsequent maintenance therapy after consolidation treatment. Cure is defined as complete remission for 10 years or negative minimal residual disease (MRD) for 5 years.

Smoldering multiple myeloma (SMM) is a precursor to symptomatic multiple myeloma that has a 10% per year of progression to symptomatic disease in 5 years with CRAB symptoms. These include hypercalcemia, renal disease, anemia, and lytic bone lesions. Dr. Jesus San Miguel recommends treating high-risk smoldering myeloma and recommends that patients consider an open clinical trial. The ASCENT trial (Aggressive Smoldering Curative Approach Evaluating Novel Therapies) is evaluating the combination of Darzalex® (daratumumab) + Kyprolis + Revlimid + dexamethasone (dara + KRd) in HRSMM in the US. Awaiting the impossible, a cure.

John DeFlice, on Twitter: @johnde1Myeloma

Bispecifics and the Hope They Bring 

Bispecifics and the Hope They Bring 

I’m very encouraged by all the abstracts related to bispecifics because they offer a unique way to attack myeloma. As we all know, myeloma is very smart and sly. It continually changes to evade the current treatment and can become more high-risk over time which complicates things even more. Finding new ways to outsmart myeloma becomes ever important as the number of relapses increases. 

Ultimately, you never want to run out of lily pads to jump to and this requires novel methods of treatment. Developing new treatments takes years of research and trials before approval is granted.   

Bispecifics are one of the most promising new ways on the horizon to fight myeloma. They attack myeloma cells in two ways. First, they identify an antigen expressed on myeloma cells, like BCMA. Secondly, they engage your circulating T cells. All this leads the drug into the malignant myeloma cell resulting in cell death. I first remember a large amount of attention on bispecifics at ASH 2018 and all the buzz was on using the BCMA antigen on the myeloma cells. 

Moving forward to 2021, BCMA bispecifics are moving forward and there is also a focus on bispecifics that use different antigens, such as GPRC5D, CD3, and FcRH5, and looking at using bispecifics in combination with existing therapies like Darzalex® (daratumumab). Regardless of the antigen, it needs to be widely expressed on myeloma cells and not on your healthy cells. 

There is the promise that in 2022, we will see the Federal Food & Drug Administration (FDA) approval of at least one bispecific. Bispecifics, like all treatments, do come with side effects. We’ve all experienced the typical side effects like fatigue, GI issues, and low blood counts, but bispecifics have a side effect most may not be familiar with — Cytokine release syndrome (CRS). CRS is a syndrome that results from the immune cells being activated and releasing large amounts of cytokines into your body. Cytokines are small proteins that help direct your body’s immune response and large numbers of them increase inflammation in the body. Much has been learned about the treatment of CRS and it has shown to be successfully controlled with medications as needed. 

This is a new treatment category that you will want to watch for in the coming months and years. I know it will be discussed in the “IMWG Conference Series – Best of ASH 2021” that you can view online beginning on Monday (https://www.myeloma.org/videos/imwg-conference-series-ash-2021) and the International Myeloma Foundation (IMF) has a terrific video series on “Using Your Immune System To Fight Myeloma” which features a segment on how bispecifics work (Myeloma and the Immune System | Int’l Myeloma Fndtn). As always, knowledge is power! 

Linda Huguelet, Chattanooga Multiple Myeloma Networking Group 

Linda Huguelet, on Twitter: @LindaMYELOMA 

The Words Are HOPE and GRATITUDE

The Words Are HOPE and GRATITUDE

As I reflect on the end of this first official day of the ASH Conference, I must say that I feel HOPE and GRATITUDE. I pored over the very complicated ASH Agenda. The IMF-SGL team of veterans and newbies is well-organized and so generous with sharing lessons, hints, and strategies to get the most out of this opportunity.

My focus was on studying the agenda and setting my personal ASH schedule, listening to pre-recorded sessions, and participating in the day’s live educational sessions. I came to this meeting hoping to see evidence of health equity and translational research from “bench to bedside to curbside.”

It is stated throughout the agenda that each program at ASH is expected to demonstrate diversity. In every part of the program, there was an expressed intentional focus on Diversity, Equity, and Inclusion (DEI). There is an Anti-racism Studio with presentations each year to raise awareness and encourage a thoughtful approach to race (ism) in medicine.

Props to Dr. Deepika Darbari (Children’s National Hospital, George Washington University School of Medicine and Health Sciences), who received an ASH award for leadership in diversity. She is engaged in the mentorship and training of underrepresented minority researchers and in advancing the care for underrepresented patient populations, primarily individuals living with sickle cell disease (SCD).

While at Howard University, an HBCU, she saw firsthand many disparity issues, such as inadequate funding, limited treatment options, and biases and stigma. She also learned about barriers to career development that minority students faced. There is hope that a new generation of scientists will bring their unique talents to the research agenda. They can use their unique perspectives to ask and answer questions that can help to unravel the mysteries of myeloma.

My educational sessions were a dive into the deep end of the pool, with a great harbinger of things to come. “High-Risk Multiple Myeloma and Treatment at Relapse” was the topic of the pre-recorded session from a Spain presenter. The live session was a series of case studies for which five international physician-scientist experts from France, Spain, and the U.S. and the audience responded to Zoom polls on the best course/s of treatment.

The session was aptly entitled “Adapting Clinical Practice to a Rapidly Changing Therapeutic Landscape.” This is one of my favorite types of sessions. It’s a reminder that myeloma is a complex disease that can require a complex response to get it under control. I was reminded of the deep pipeline of ongoing myeloma research and of the need to adapt treatment to the individual, their type of myeloma, and their lifestyle.

The “HOPE” is that there are approved treatment options or clinical trials for almost every scenario. The need for continuous education for multiple myeloma specialists, community oncologists, and primary care doctors is crystal clear. I HOPE one day that the protocol for any physician who treats myeloma is that they schedule a telemedicine conference that includes the patient.

These specialists respectfully disagreed on several points, but we were able to hear and appreciate their reasons for the divergence. It was like a Masterclass for the physicians/clinicians in the audience. We could see from the polls their votes on the appropriate regimen – pre-and post-presentation. In some cases, there was a dramatic change in their opinions.

In addition to the regimen, the presenters did not shy away from the expense related to some treatments versus others and the availability of certain drugs. Insurers can sometimes determine whether a particular treatment will be approved. Some prerequisites for regimens make them inaccessible to entire populations of myeloma patients.

So, there is much to be about. This first day heightens my HOPE for a cure. I am eternally GRATEFUL for the curious and determined researchers, physicians, providers, patients, caregivers, and sponsors, and others who together move us towards a cure.

Gail G. McCray, on Twitter: @IMFgailMyeloma

Myeloma researchers and experts from around the world present and discuss case studies.