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

The Amazing Power of Proteins (and RNAs too)

The Amazing Power of Proteins (and RNAs too)

In my scientific career as a protein scientist studying protein misfolding, I’ve always been a little protein-centric in my view of biology. It’s a bit ironic because I work at an academic institution that is an RNA mecca, where many of my colleagues are doing amazing research understanding the role of RNAs in biology.  

Simplistically, proteins do all the work in the cell. DNA gets all the glory, but RNA is the master regulator controlling the fate of each cell. How exciting it was for me to see proteins (specifically antibodies) playing such a major role in myeloma treatment on this first day of #ASH21! 

One of the biggest take-home lessons for me today: Darzalex® (daratumumab) is the current “darling” of myeloma treatment strategies. Maybe I’m being biased because I love proteins, but it was awesome to see proteins as powerhouses of therapy in myeloma. There were many talks that discussed clinical trial data showing daratumumab and other CD38+ antibodies’ increased progression-free survival when added as a 4th agent to standard triplet regimes in newly diagnosed patients or when included as part of a new triplet regimen for relapsed myeloma.  

During the International Myeloma Foundation sponsored session on “Adapting Clinical Practice to a Rapidly Changing Therapeutic Landscape in Multiple Myeloma”, there was a related thought-provoking discussion led by Dr. S. Vincent Rajkumar (Mayo Clinic – Rochester, MN) on the importance of shared decision-making between myeloma patients and their myeloma specialists when making decisions about next steps in treatment because of the complexity of issues that each patient faces. 

For patients who are refractory to immunomodulators, proteasome inhibitors, and CD38+ antibodies, clinical trial data reported showed BCMA-targeted therapies to be very promising, with response rates of >60% in heavily pretreated myeloma patients. These therapies include FDA-approved CAR T cells and the antibody drug conjugate Blenrep® (belantamab mafodotin), which has a manageable ocular toxicity. Additionally, several bispecific T cell engagers (BiTEs) are anticipated to obtain FDA approval in the next few years. These BCMA-targeted therapies are changing the treatment landscape for relapsed/refractory myeloma and providing new hope. 

I found myself thinking a lot about shared decision-making between a myeloma specialist and a patient whenever there is a progression of disease. Making a next therapy decision is a very personal decision — influenced by toxicities, comorbidities, cost, access to care and so many other things. For me, I tend to want to focus on hitting my myeloma hard to prevent the development of drug-resistant clones so I can be around long enough to see my four kids become thriving adults.  

I’m grateful that I moved to a combination CD38+ antibody/immunomodulator/steroid therapy line at the very first hint of relapse, right when the pandemic started. I am so grateful for my myeloma specialists, Dr. Muthalagu Ramanathan (UMass Memorial Health Care – Worcester, MA) and Dr. Giada Bianchi (Dana-Farber Cancer Institute – Boston, MA) who have helped me navigate my own therapy decisions. 

I enjoyed following the #ASH21 meeting on Twitter, including attending my first @TwitterSpace today hosted by Dr. S. Vincent Rajkumar. I also smiled when I read this tweet about a talk by Dr. Nina Shah(University of California – San Francisco, CA) : 

I’m glad that my myeloma specialists and I are “cool,” as I am using daratumumab for a 2nd line. I’m also excited about all these other key points about treatment options for relapsed/refractory myeloma, and I am looking forward to learning about other new targets in the pipeline, like CELMoDs and other immunotherapies in the days ahead. 

Today, I heard data that made me even more confident about my decision to start a new line of therapy 21 months ago. I learned that circulating tumor cells predict risk of progression for smoldering myeloma patients. I also really enjoyed a talk by Dr. Giada Bianchi which discussed the role of the tumor microenvironment in the progression from MGUS to SMM to myeloma. I enjoyed thinking about how changes in the bone marrow milieu can influence progression of myeloma, and it was striking to me that changes in both protein and miRNA levels were playing a role in this interaction between the bone marrow components and the plasma cells in a way that leads to progression.  

Specifically, bidirectional exchange of exosomes (vesicles that deliver lipids, proteins and nucleic acids) between myeloma plasma cells and components of the bone marrow niche supports pathogenesis. As a scientist, it makes sense to me to hit my myeloma hard to limit the development of new myeloma clones, and I’m so grateful that I, so far, have been able to manage the side effects of treatment and to continue teaching that I love. 

It seems like proteins are indeed becoming powerful players in the development of new therapies, and new technologies like single-cell RNA sequencing will also help develop new biomarkers and therapies for myeloma patients with aggressive disease.  

Yay Proteins! Yay RNAs too!  

Jill Zitzewitz, PhD, on Twitter @JillZitzewitz