Power Over Your Mind

Power Over Your Mind

“You have power over your mind – not outside events.  Realize this, and you will find your strength.”—Marcus Aurelius, Meditations

As the 63rd annual meeting of the American Society of Hematology (ASH) wrapped up this week, I am looking to the future with hope and excitement. I admit my brain is a bit tired from trying to process all the technical data, but I am trying to have power over my mind!

Since I have relapsed twice in my 10 years of living with multiple myeloma, I tend to be very interested in any studies or information pertaining to my options at relapse.  This chart shows that there are many options and combinations available.

This year’s ASH had many updates on key clinical trials. Many of the trials were for heavily pre-treated patients who are running out of options.  My other teammates have summarized this information better than I could.  However, there was one presentation by Dr. Thomas Martin (UCSF Helen Diller Family Comprehensive Cancer Center – San Francisco, CA) with an update on the CARTITUDE-1 trial that got my attention. This is a study of a B cell maturation antigen (BCMA) directed CAR T-cell therapy called Ciltacabtagene autoleucel (cilta-cel) for heavily pre-treated, relapsed/refractory multiple myeloma patients.  When Dr. Martin took the stage, you could see the excitement in his face.  He was excited to present the data but more importantly, I think he was happy to be there, presenting to his colleagues who were able to attend in-person.  

At the International Myeloma Foundation (IMF) Best of ASH presentation, Dr. Brian G.M. Durie (IMF Chairman of the Board) commented that cilta-cel could have FDA approval by the first or second quarter of 2022.  

Last year’s ASH was all virtual.  I watched everyone make their presentations virtually.  And it is just not the same.  Even though we were virtual this year, you could sense the excitement from those who were there in-person during their presentations in front of colleagues. 

For those able to attend this year’s ASH in-person, it must have seemed like a family reunion.  So many doctors tweeting out pictures with friends or colleagues whom they haven’t seen in 2 years.  And all these myeloma doctors and researchers from all over the world work so hard to find ways to treat and hopefully, cure multiple myeloma one day.  I am in awe of what they do, and I am deeply grateful for their dedication.  

Finally, I was amazed by the Support Group Leaders’ participation in the International Myeloma Foundation’s (IMF) ASH team this year.  As I go back and read their blogs, I was amazed at the diversity of the topics. I urge you to take some time to read their blogs.  They are all so very interesting, and all from a slightly different point of view.  That’s what makes us a great team!  

Stay well and stay strong!

Sheri Baker, on Twitter @blondie1746 

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 

#ASH21 Trial Design Acronyms

#ASH21 Trial Design Acronyms

I was going to write something insightful – my biggest takeaways – from the last two days of the 63rd annual meeting of the American Society of Hematology (ASH) meeting. I started saying that: 

  • the MASTER trial was very patient-centric; it had over 23% African Americans enrolled in the trial, the MRD response adopted treatment secession strategy is innovative, the trial enrollment was enriched and powered for high-risk patients, and the MASTER-2 trial design is future-looking, the result of 
  • the GRIFFIN trial could be setting quadruplet (dara-RVd) standard of care for high-risk patients in those countries where dara is approved and can afford it
  • the near 100% ORR, deepening stringent complete response (sCR) at year 2, results of CARTITUDE-1 are going to be game-changing and an indicator that myeloma has indeed entered the era of immunotherapy 
  • the OPTIMUM data showed the benefit of adding a CD38 to a quadruplet for those prospectively identified as having ultra high-risk disease by gene expression profile (GEP) 

Then I said, what were the drugs in the GRIFFIN trial again, and what are the randomization criteria for those trials with one?  That is when I pivoted to collecting the trial design in one place for some of the clinical trials presented or referenced at #ASH21.  Below is a non-exhaustive list of trial designs for us clinical trial mortals. In no particular order: 

OPTIMUM [Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, Dexamethasone (Dara-CVRd), V-Augmented Autologous Stem Cell Transplant (V-ASCT) and Dara-Vrd Consolidation in Ultra-High Risk (UHiR) Newly Diagnosed Myeloma (NDMM) and Primary Plasma Cell Leukemia (pPCL) Compared with Myeloma XI/XI+ Trial Treatment for Uhir MM: The UK Optimum/Muknine Trial (Clinically Relevant Abstract)]

MASTER [Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone (Dara-KRd), Autologous Transplantation and MRD Response-Adapted Consolidation and Treatment Cessation. Final Primary Endpoint Analysis of the Master Trial] 

CASSIOPEIA [Daratumumab (DARA) with Bortezomib, Thalidomide, and Dexamethasone (VTd) in Transplant-Eligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Analysis of Minimal Residual Disease (MRD) Negativity in Cassiopeia Part 1 and Part 2]

MAIA [Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): a randomized, open-label, phase 3 trial]

Forte [Evaluation of the Safety and the Efficacy of Carfilzomib Combined With Cyclophosphamide and Dexamethasone (CCyd) or Lenalidomide and Dex (CRd) Followed by Autologous Stem Cell Transplant (ASCT) or 12 Cycles of Carf Combined With Dex and Len for Patients Eligible for ASCT With Newly Diagnosed Multiple Myeloma] 

GRIFFIN [Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma]

GMMG-HD6 A Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG-HD6)

GMMG-HD7 Trial on the Effect of Isatuximab to Lenaliodomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7)

CARTITUDE-1 A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma. Please note there are now CARTITUDE-2, 3, 4, and 5 in progress. You can read about them at clinicaltrial.gov site 

CC-220-MM-001 [Iberdomide (IBER) in Combination with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Dose-Expansion Phase of the CC-220-MM-001 Trial]

Bb21217 [Study CRB-402 a BCMA-Targeted CAR T Cell Therapy, bb21217 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb21217 in adults with relapsed/refractory multiple myeloma (MM). KarMMa is the bb2121-MM-001, the original bb2121 study]

MajesTEC-1 (Phase 1/2 Study of Teclistamab, a B-Cell Maturation Antigen x CD3 Bispecific Antibody, in Relapsed/Refractory Multiple Myeloma)

iStopMM [A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM) (iStopMM)]

I hope this list of clinical trial design in one place will be helpful for patients, advocates, and those who don’t always speak myeloma. 

Sharing The Hope!  

Yelak Biru, on Twitter: @NorthTxMSG