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 

Off the Beaten Path

Off the Beaten Path

There are so many amazing programs available to attend at the American Society of Hematology (#ASH21) meeting.  Scientific and Clinical Education spotlights, award ceremonies, poster and oral abstracts covering everything from “bench to bedside,” and beyond.  Many of the sessions of interest overlap, historically making it a challenge to choose which session to attend. The virtual/hybrid model is quite handy, as it allows for people to go back and view sessions they missed.  

For good reason, there is much reporting on studies looking at drug development and updates in combination therapy in myeloma.  I will be reporting on some of these in my next blog. However, for this blog, I want to focus on some of the sessions not frequented based on title or content, but for some of the readers, the information may be quite relevant.

There was a presentation on Sunday, December 12, by Dr. Jason Valent (Cleveland Clinic —Cleveland, OH) in the 653 session: Myeloma and Plasma Cell Dyscrasias: Clinical-Prospective Therapeutic Trials; treatment of NDMM and amyloidosis patients.  The topic of interest was a drug in development for light chain amyloidosis (AL). The current available treatment approach is to stop the production of light chains that deposit into tissue by using chemo- and immuno- therapy to prevent further tissue damage.  

However, this does not remove the deposits and damage already created.  This monoclonal antibody targets fibrils already deposited, binds to a neo-epitope — leading to the removal of fibril deposition.  It’s VERY exciting to take a dual approach to treating this nasty plasma cell disorder.  Dr. Valent valiantly expressed that this monoclonal antibody is “incredibly safe” – the cardiac safety profile was exceptional, and the addition of dara did not alter pharmacokinetics of CAEL-101.

468 Safety and Tolerability of CAEL-101 in Combination with Anti-Plasma Cell Dyscrasia Therapy in Patients with AL Amyloidosis: 1-Year Results from an Open-Label Phase II Trial (Dr. Jason Valent, Cleveland Clinic) 

On Monday, December 13, there were two presentations in the 902. Health Services Research—Lymphoid Malignancies: Cost of Care & Cost Effectiveness session that really caught my attention. They both have the potential for “real-clinic” impact, both in saving money and patient time.  

Paper Number: 665 Trends in Utilization of Stored Cryopreserved Autologous Peripheral Hematopoietic Cells (APBHC) Intended for a Second (or beyond) Autologous Hematopoietic Cell Transplantation (AHCT) in Patients with Multiple Myeloma (MM): A Single Center Experience presented by Dr. Farah Yassine, MD,MSc (Mayo Clinic — Jacksonville, Florida)

Dr. Yassine did a retrospective review of cryopreserved (stored) stem cell collection usage at Mayo Clinic-Florida from 2010 to 2019.  Nearly 92% of patients who underwent stem cell collection and first transplant had cells in storage for a possible second transplant. 

 However, usage for a 2nd transplant has continually decreased.

The financial and time expenditure for cryopreserved cells was estimated.

There was a good discussion following this presentation.  It was noted that this is one center’s analysis for cost, and that the cost of prolonged storage is absorbed by the medical institution. 
In the era of CAR T therapy and related cytopenias, stored stem cells may have greater utilization. However, as CAR T moves earlier in the treatment sequence, cytopenias may not be as much of an issue. 

Again, it was noted, this is discussing stem cell storage for a second (salvage) transplant, not a delayed or planned tandem transplant. Likely, only one transplant will ever be performed and additional collection for multiple delayed transplants is not needed. This has potential for time and cost savings.   

This was followed by Paper Number 666Decreasing Costs and Clinic Wait Time While Maintaining Safety for Patients Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD) for Multiple Myeloma, presented by Eno Inyang, PharmD (Dana-Farber Cancer Center — Boston, MA).

For those of you who have received VELCADE® (bortezomib), REVLIMID® (lenalidomide) and dexamethasone (VRd) therapy, you are familiar with the weekly (or twice a week) routine – go to the lab, wait to be called; get blood drawn, wait for results; go to infusion center, hope the results have been received and reviewed; then finally, get your Velcade injection.  And how often do those results impact your ability to get your Velcade injection, and what cost (time/money) is this to you?  This study looked at exactly these concepts: 

It is well-known that people can experience decreased neutrophils in absolute neutrophil count (ANC) and platelets from VRd therapy.  However, if patients had ANC>1,000 and Platelet count >75,000 on Day 1 of their cycle, additional labs prior to each dose were not needed, and would be checked with Day 1 of subsequent cycles.  

They went on to validate their findings by implementing a workflow in their clinic. 

Time saved – patients spend >50% of their time in clinic waiting for labs:

Money saved – the cost of the lab services and blood processing: 

The discussion was, again, very robust after this presentation. This has real implications for time and cost savings for so many.  However, as daratumumab becomes more incorporated into frontline therapy (Abstract #79: GRIFFIN Trial, Dara+VRd, presented by Dr. Jacob Laubach, Dana-Farber Cancer Institute — Boston, MA), additional analysis will be needed. 

I continue to sift through the wealth of information provided at the 63rd annual ASH meeting. As discussed in my Pre-ASH blog, I want to review the “one-off” aspects of myeloma (such as high-risk components and extramedullary disease) and capture these in my next post.

Thanks for reading. Please follow me and the other support group leaders on social media.

Teresa Miceli, RN BSN OCN  
Myeloma Nurse Navigator,
Mayo Clinic – Rochester 
IMF Nurse Leadership Board
Rochester MMSS, Facilitator 

Teresa Miceli, on Twitter @IMFnurseMYELOMA 

ASH 2021 Day 1: From Iceland to Bispecifics

ASH 2021 Day 1: From Iceland to Bispecifics

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

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 

Symposium Day: Insightful Comments from Myeloma Specialists

Symposium Day: Insightful Comments from Myeloma Specialists

The Friday before the official start of ASH is always considered as Symposium Day. Symposiums typically last a couple of hours and involve several myeloma expert doctors discussing patient cases and various treatment options. Patient cases can vary from smoldering to newly diagnosed, to early and late relapse, and along with them — the consideration of risk factors and comorbidities.

These meetings are sponsored by advocacy organizations: the International Myeloma Foundation, Healthtree Foundation, Research To Practice, as well as Pharma companies. While they don’t include new information that will subsequently be presented at ASH, they provide treatment suggestions currently approved by the FDA as well as consideration of ongoing clinical trials.

In particular, my goal was to listen for insights provided by the specialists and to offer those takeaways in this blog. 

After attending 3 symposiums, here’s what I heard:

  1. At an Education Program discussing high-risk MM (HRMM), Dr. María V. Mateos (University of Salamanca – Salamanca, Spain) remarked: “While there’s no specific treatment for HRMM, our goals should be to provide continuous therapy and focus on getting MRD (minimum residual disease) as low as possible.”
  2. Dr. Suzanne Lentzsch (Columbia University Medical Center – New York) noted an important study from Dr. Rafael Fonseca (Mayo Clinic, Rochester, MN) which showed “that 57% of non-transplant eligible patients only get 1 Line of Therapy, so many patients are not getting newer treatments.” [Personally, I’m trying to track down this report.]
  3. Dr. Noa Biran (Hackensack University Medical Center – Hackensack, NJ), when treating relapsed MM, suggested using the TRAP algorithm when making subsequent treatment decisions. T=Timing of relapse; R=Response from prior therapy; A=Aggressiveness of disease; and P=Performance status. This algorithm was reiterated by Dr. S. Vincent Rajkumar (Mayo Clinic, Rochester, MN).
  4. Dr. Biran also noted that “triplets outperform doublets in early relapse.”
  5. Dr. Philippe Moreau (University Hospital Hotel Dieu — Nantes, France) noted that an upcoming study for newly diagnosed MM will show no benefit of adding Ninlaro® (ixazomib) to Rev-dex maintenance.
  6. For non-transplant eligible patients, Dr. Moreau noted: “I think DaraRd till progression [Maia study] is the best treatment for elderly patients. Dr. Rajkumar countered “But VRd for 6 months, then Rev maintenance is more cost-effective, easier on the patient, and also provides excellent results so either treatment choice is okay.”
  7. Dr. Rajkumar’s principles for selecting treatments for relapsed MM: 1) use a triplet; 2) change 2 drugs; 3) consider a transplant; 4) consider a clinical trial.
  8. Dr. Thomas Martin (University of California SF – San Francisco, CA) predicted: “Ultimately bispecifics will be used in all lines of therapy and CAR T will replace transplant.”
  9. Dr. Morie Gertz (Mayo Clinic — Rochester, MN)  “If Blenrep® is working, don’t give up due to ocular side effects. Rather, try dose adjustment, give less frequently, even adding prednisone has helped with eye effects…don’t give up.”
  10.  For triple-class refractory patients, both Drs. Martin and Gertz commented that the alkylating agent cytoxan should be considered if it hasn’t been previously used.

That’s it for tonight.  My first meeting tomorrow is at 3:30am PST so it’s early to bed for Day 1 of ASH!

Be your own best patient advocate.

Jack Aiello, on Twitter @JackMAiello