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 

ASH Day 3: It’s a Wrap!

ASH Day 3: It’s a Wrap!

December 13, 2021 – Today was the final day of ASH but it was still full of information, and to be honest, I’m a bit brain-fried.  The day began with the IMWG Conference series (with the replay available on the IMF website). I jotted a few quotes that I found interesting:

IMF Chairman of the Board Dr. Brian G.M. Durie noted that he expects “mass spec will be rolled out in the next year or so.” We’ll see it as a blood test called “Exent” from The Binding Site, which designed the original free light chain test. For many, the results on Exent may be used instead of minimal residual disease (MRD) testing via a bone marrow biopsy.

Dr. Thomas Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA) remarked: “We at UCSF are considering 4-drug therapy Griffin (dara + RVd) to be the new standard of care for transplant-eligible multiple myeloma patients, pending insurance coverage for the dara.”

Dr. Maria-Victoria Mateos (University of Salamanca — Salamanca, Spain) commented: “CELMoDs such as iberdomide will replace immunomodulatory drugs (IMiDs) Revlimid® (lenalidomide) and Pomalyst® (pomalidomide).”

Dr. Martin: “We’ve seen poor responses to the COVID-19 vaccine for patients on anti-B cell maturation antigen (anti-BCMA) and anti-CD38 treatments, but some patients have efficacy after their booster shot. Stopping CD38 treatment for a period of time doesn’t appear to improve booster benefit.”

And now for a few of my takeaways from today’s ASH (all treatments for relapsed/refractory multiple myeloma (RRMM) patients unless otherwise noted:

  • Dr. Jonathan Kaufman (Winship Cancer Institute, Emory University — Atlanta, GA) presented early results from a trial comparing venetoclax plus dara and dexamethasone (VenDd) vs Velcade®(bortezomib) plus dara-dex (VenDVd) for RRMM and found an overall response rate (ORR) improvement of 20+ points (87% vs 63%) [817] 
  • This study examined outcomes of RRMM patients (pts) following treatment of bispecific antibodies and concluded for N=57 pts that getting another T cell directed therapy significantly improves median progression free survival (PFS) (mPFS:19 vs 2 months) and OS (NR vs 12 mos) [821]
  • For clinical trials, it was proposed that PFS and QoL measures be co-primary endpoints rather than just PFS since many MM patients favor one over the other. [836]
  • Dr. Sham Mailankody (Memorial Sloan Kettering —Commack, NY) presented another CAR T study of MCARH109 that targets GPRC5D (not BCMA) and CD3, and eligible patients included those with prior BCMA therapy (inc CAR T as well as allo-SCT). N is small at 16 but 69% had ORR (inc 25% CR) with similar ORR for prior BCMA/CAR T. [827] 
  • For N=55, this bispecific called elranatamab from Pfizer achieved 69% ORR at the recommended phase 2 dosage (RP2D) [895]
  • Dr. Philippe Moreau (University Hospital — Nantes, France) presented results of teclistamab, another bispecific, from a study called MajesTEC-1. For N=165, ORR=62%, CR=29%, 9-mos PFS = 59% and MRD- is 17% (10-6). Dosage is .06 -> .3 mg/kg, using a step-up dosing to minimize side effects such as cytokine release syndrome (CRS), which were all grade 1/2. [896]
  • The DREAMM-5 study showed that combining Blenrep® (belantamab mafodotin-blmf) with a T cell Co-stimulator Agonist aICOS resulted in increasing single agent Blenrep ORR from 32% to 52% without increasing side effects. [897]
  • Another bispecifc ABBV-383 (previously called TNB-3838) targets BCMAxCD3. For N=76 at the RP2D (40mg via IV), ORR was 81% with >= VGPR of 69%, although for triple-class refractory, ORR dropped to 53%. [900]

Finally, there were a couple of interesting abstracts 665 and 666 that looked at the cost of saving stem cells for a 2nd transplant and the cost /wait times for doing blood draws (CBC and chem panel) before every Velcade infusion as part of RVd treatment. At Mayo Clinic-Florida, only 2% of patients get a 2nd transplant but the cost of harvest and cryopreservation totals $8 million for all their patients (average 4 years storage). And changing protocols to perform blood draws only once per cycle can save $1,500 and 3-4 hours wait time per draw times the number of draws previously done per cycle.

Well, that’s it for 2021 ASH, although I’ll likely created a blog with my final thoughts, as well as a multipage write-up for anyone that wants it.  This “virtual” hybrid platform worked for the most part, though I do miss connecting face-to-face with others. Perhaps that will happen at the 2022 ASH in New Orleans.

Be your own best patient advocate.

Jack Aiello, on Twitter @JackMAiello

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

Pre-ASH Blog: Virtual to Hybrid: 63rd ASH Annual Meeting and Exposition to Highlight Progress of Critical Research

Pre-ASH Blog: Virtual to Hybrid: 63rd ASH Annual Meeting and Exposition to Highlight Progress of Critical Research

On December 12, 2021, there were 545 open and recruiting clinical trials on the clinicaltrials.gov website. There are over 800 #ASH21 abstracts with the word #myeloma in them.  There was a four-fold increase in Google’s keyword trend for #myeloma after the death of Secretary of State General Colin L. Powell. Over 750,000 men, women, and children have died in the US and over 5 million worldwide due to the #COVID19 pandemic. Delta and Omicron COVID variants continue to humble and teach us that collaboration is key to overcoming. 

Google Keyword Search Trend for Myeloma 

The FDA approved the first BCMA-targeted CAR T-cell therapy for multiple myeloma, Abecma® (idecabtagene vicleucel). The hopeful approval for the second CAR T, cilta-cel, had been delayed by three months but is expected in Q1 of 2022.  

The American Society of Hematology (ASH) 63rd Annual Meeting and Exposition will be held from December 11-14 in hybrid mode. As in previous years, the International Myeloma Foundation will be sending 13 support group leaders. Just like last year, these leaders will attend the conference virtually.  

This year’s ASH will highlight the progress of several critical research: 

  • MGUS and SMM – Is screening the way to go? What is the psychological impact of “knowing early?” Are African Americans at a higher risk for MGUS and as a result, myeloma? What is the effect of high-dose treatment for SMM patients? 
  • MRD-guided therapy – Can we use MRD to pause treatment? What is the impact of quadruplets on MRD? 
  • CAR T, BCMA therapies – What are the outcomes of phase 1/2 or 2/3 studies for CAR T and BCMA, such as teclistamab, and others that don’t even have a name yet? How about off-the-shelf CAR Ts to alleviate collection and production issues of CAR Ts? 
  • Maintenance – Is maintenance the way to go? Which single or double is best for maintenance? How about QOL, affordability, and impact on subsequent therapies? 

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

  • The Friday IMF Satellite Symposium  
  • International Myeloma Working Group (IMWG) Breakfast   
  • IMWG Conference Series  
  • Global Myeloma Action Network (GMAN) Summit  
  • Best of ASH Conference  

The IMF SGLs will be attending ASH virtually, so we won’t have that awkward moment of fist-bumping while someone else is extending a handshake!  

Yelak 

Sharing The Hope! 

Yelak Biru, on Twitter: @NorthTxMSG 

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