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  

Searching for the ‘Magic Wand’

Searching for the ‘Magic Wand’

What a whirlwind of information it was this weekend! #ASH21 #IMFASH21  

We learned about new and exciting studies related to monoclonal gammopathy of undetermined significance(MGUS) smoldering myeloma (particularly high-risk), and then active myeloma. I am so blessed to be able to participate in these presentations and gain this new level of insight into the myeloma world.

As a current high-risk myeloma patient with two young children, I started out as high-risk IGA MGUS and then developed high-risk smoldering myeloma (SMM). However, I continue to hope for a “magic wand” (as my son says) to cure this disease.  Therefore, I am writing this blog from that perspective: (1) to encourage other multiple myeloma patients and caregivers, especially those with young children; (2) to provide uplifting information; and (3) to empower those with myeloma through these new educational resources.

As a previous high-risk IGA MGUS patient who had it for almost five years, the new studies out of Iceland with the iStopMM (Iceland Screens,Treats, or Prevents Multiple Myeloma) Study showed the importance of tracking MGUS.  Depending on which type of MGUS you have, MGUS may have a greater tendency to turn into active disease.  The iStopMM Study demonstrates the importance of tracking the disease so that doctors can monitor who may or may not progress into a different stage. Tracking the disease at an early stage allows myeloma patients and their medical team to monitor it carefully and decide when and if to move on to doing treatment. With early detection, a person can hope to avoid certain struggles and issues that they could face without early treatment.  

If a patient moves from MGUS to smoldering myeloma, wow! What choices are coming down the road!  Very exciting!  As a patient who went from high-risk smoldering myeloma to active myeloma within 8 months, it is so encouraging to see the latest studies that show the benefits of treatment on high-risk SMM. It used to be that many high-risk SMM patients would use the “watch and wait” approach.  While that still is a viable option (as there are considerations of starting therapies), it seems that there are some great outcomes when treating high-risk SMM patients.  Some studies are showing promising results by using Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone (also known as KRd) and even KRd with a stem cell transplant. [Carfilzomib, Lenalidomide and Dexamethasone (KRd) as Induction Followed by HDT-ASCT, Consolidation with KRd and Maintenance with Rd.  GEM-CESAR, paper 1829.]

If the patient then goes into active myeloma, again – I just have to say, wow!  There are all sorts of options!  There were a lot of presentations that added daratumumab to various drug combinations. From a non-medical standpoint, it seems that in most cases, Dara added to these various drug combinations increased the survival rates and deepened the responses.  However, for some patient groups, Dara wasn’t always the “magic wand.” While Dara may still help that segment of myeloma patients, it was not as effective as it was in other groups.  But overall, it was great to know about the effectiveness of the drug, and how Dara provides another available option in the treatment arsenal in this myeloma journey.

Another interesting topic point was the discussion on CAR T therapy and minimal residual disease (MRD) negativity.  CAR T therapy may be another treatment option for myeloma patients that could beneficial. Again, looking at it from a lay person’s perspective, it seems that CAR T therapy has advanced and some of the side effects have gotten a bit better. The stats related to progression free survival (PFS) and overall survival is amazing!  It is also exciting to see how CAR T affects MRD negativity. MRD negativity seems to be a key factor in a person’s success in their myeloma journey. It is interesting to see how CAR T continues to develop as part of the myeloma treatment plan.

One of the primary outcomes of attending ASH this weekend was gathering INFORMATION!  While I may not completely understand the ins and outs of the therapies, drugs, side effects, charts, stats, and everything else (my head is still spinning!), ASH provides the latest information that allow for intelligent and meaningful conversations with the medical/treatment team.  

Information allows myeloma patients to be empowered, be their own advocate, and partner with their healthcare team to help make the right decisions with current available information.  By learning more about different treatment options, myeloma patients can ask questions like: Is the current treatment plan still the best approach?  Are there novel advances that may work better at the current stage of myeloma? Is now the best time to hit myeloma harder?  For all these questions, I have no answers.  But, by learning about new treatment options and therapies, myeloma patients are empowered to talk to their doctors about options and to see if status quo is the way to go or if there are any changes that should be considered based on the new research.  

Furthermore, as most people on this journey know, each person’s path is unique and can change at any moment.  I believe that partnering with your medical team is key to understanding what is right for each person’s situation and their type of myeloma.  This concept was supported by some of the studies which are researching the need for personalized therapies. [A Machine Learning Model Based on Tumor and Immune Biomarkers to Predict Undetectable Measurable Residual Disease (MRD) in Transplant-Eligible Multiple Myeloma (MM), Paper 1596.]

I have learned so much this weekend!  It was interesting to see the developments that are happening within the myeloma community.  The treatments are advancing every day.  Hopefully, one day, we will find that “magic wand.”

My son and what he would love to be his magic wand!

Sue Massey, on Twitter @Mmfamilies_IMF

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

To Treat or Not To Treat?

To Treat or Not To Treat?

The IMF CCO CME Friday Satellite Symposia is a physician educational activity that is available for those who register, either for the online virtual or in-person option.  

The diagnosis of active multiple myeloma (MM) and when to initiate therapy for patients with MM continues to evolve as we learn more about the biology of this disease and how we can use various biomarkers to determine the risk of progression to active disease. 

Currently, some consider beginning therapy for patients with smoldering multiple myeloma (SMM) once they have >50% risk of progression to active disease based on the 20/2/20 model. Some healthcare professionals feel uncomfortable and do not wish to start treatment for high-risk smoldering multiple myeloma (HRSMM), and ongoing monitoring happens. Today, we are hearing that we need more than the 20/2/20 model to determine treatment for HRSMM. 

I’m sure some of the other #IMFASH21 Team Leaders will blog on other cases presented at the Symposium, but I’ll focus here on the HRSMM. Below is the excellent agenda for the IMF Symposium where 6 cases were presented, voted on, discussion ensued, voted on again.   

Dr. Jesus San-Miguel (Clínica Universidad de Navarra – Pamplona, Spain) presented virtually on “Case Study 1: Evidence for Treating HRSMM.”

To Treat or Not to Treat for HRSMM: 

When I was diagnosed 21 years ago, there was not even a classification of HRSMM vs SMM. I remember at previous ASH when these discussions and research first started and the interest that developed. Today we have from the International Myeloma Working Group (IMWG) progression risk by group, see below: 

“Having these tools helps a SMM determine to treat or not to treat – but you need more than 2/20/20!” – Dr. Jesus San-Miguel.

Today, my rock n’ roll reference song is “Treat Me Right” by Pat Benatar (1980).

Enjoy! 

Michael Tuohy, on Twitter: @IMFmikeMYELOMA 

Pre-ASH Blog: To Think What Nobody Else Has

Pre-ASH Blog: To Think What Nobody Else Has

Research is to see what everybody has seen, and to think what nobody else has.” 

Albert Szent-Gyorgyi

I tweeted the above quote after Dr. Ola Landgren (Sylvester Comprehensive Cancer Center at the University of Miami — Florida) had spoken to our International Myeloma Foundation (IMF) virtual support group in New Mexico.  

Dr. Landgren, a myeloma expert, discussed new myeloma treatments and shared his new lines of research at the Sylvester Comprehensive Cancer Center in Miami—South Florida’s only NCI-designated Cancer Center. Listening to Dr. Landgren speak to our group reminded me of just how far myeloma researchers and clinicians have come in the development of myeloma treatments.  

Thalidomide was first introduced as a myeloma treatment at the University of Arkansas by Dr. Bart Barlogie. Back then, the five-year survival for a newly diagnosed myeloma patient was 34% nationally. With the therapeutic advances today, we can look to overall survival from 1-3 years to 10-20 years. We also have a tremendous amount of excitement about the possibility of curing myeloma by treating high-risk monoclonal gammopathy of undetermined significance (MGUS) and high-risk smoldering myeloma (HRSMM).

Since my diagnosis in 2010, I have become so encouraged by the various treatment advances. Such advances include CAR T-cell therapy, novel bispecific antibody therapy, and new modalities to measure minimal residual disease (MRD) in early relapsed disease, along with improved imaging techniques.  

Also, the advancement of genomics in multiple myeloma suggests that targeted treatment may become available in the future. I’m very excited to hear about all the research that will be presented at ASH 2021, and I am especially grateful to be part of this conference as an IMF support group leader.

John DeFlice, on Twitter: @johnde1MYELOMA