Dec 15, 2024 | Linda Huguelet
This year’s American Society of Hematology (ASH) Annual Meeting was filled with fascinating new treatments and treatment combinations which left me thinking that there is so much more information to digest as a patient than when I was diagnosed in 2010. Over my 14 years as a myeloma patient, I’ve been through 5 lines of therapy. In conjunction with my specialists and local hematologist, I’ve made treatment decisions over the years at each relapse. I used the available information to help me have a candid discussion with my physicians before coming to a decision. Several of the options seemed fairly obvious at the time, given the more limited number of choices.
In 2010, there was no question that Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone was the way to go for upfront treatment. It was somewhat comforting that there wasn’t a need to decide on a treatment plan on day 1 when your head was still spinning from the fact you had cancer and all the new terminology. If you were transplant-eligible, it was basically assumed you would do this following your upfront cycles.
In 2024, the standard of care for a newly diagnosed patient is a combination of 4 medications which includes the addition of a monoclonal antibody – Darzalex (daratumumab) or Sarclisa (isatuximab). Which is best for each individual patient? These combinations have proven to produce very deep responses in most, so is there a need for a transplant upfront or ever? Some physicians still favor transplant, some say save it for relapse, and some aren’t convinced the exposure to the high dose chemotherapy is necessary.
At this year’s ASH, TECVAYLI (teclistamab) was presented in several abstracts as a possible future option in upfront and maintenance therapy. This drug is currently only used after multiple lines of therapy. If the trials prove this out and it gets approved by the Federal Drug Administration (FDA), this adds yet another layer of complexity to the treatment sequencing puzzle. The passion the researchers display at ASH is comforting because they are doing everything they can to provide more and better options for myeloma patients. On the flip side, this makes the need to have a myeloma specialist on your team essential to help understand the options and help you evaluate the options.
At my first Support Group Leader Summit in 2011, I vividly remember Susie Durie standing before the group and exclaiming that knowledge is power! She encouraged us to be as informed as possible and be an advocate for ourselves during your entire myeloma journey and to encourage our support group members to do the same. Those words could not ring truer today. Thanks to the International Myeloma Foundation (IMF), we have the tools to be informed. Take advantage of reading the blogs from all participants in this year’s meeting because each provides information for you to consider, call the InfoLine, ask Myelo questions on the IMF website, register for the December 18th webinar (IMWG Conference Series – Making Sense of Treatment) — do whatever works best for you to stay informed and on top of the latest developments. This will help you put all the myeloma pieces of the puzzle together more easily!
Linda Huguelet, Chattanooga Multiple Myeloma Networking Group
@LindaMYELOMA
Dec 12, 2024 | Terry Glassman
I am traveling today and then a very busy treatment day, so I’m going to do a quick post-ASH blog. Yet, if you want to hear more in-depth, check back because I promise another blog within a week.
First off, one of my fellow patients who follows me asked, “it must be hard listening to all this information.” Honestly, it was not; it was encouraging and hopeful. As I’ve mentioned before, my Myeloma Specialist told me on my first visit; “The longer I keep you alive, the longer I can keep you alive.” That sentiment stayed with me throughout ASH. It was palpable as I listened to the latest research and advances in treatment…hopeful progress everywhere!
It was heartening to see how dedicated these physicians and scientists are. So many brilliant minds sharing, questioning, and learning from each other! Sure, at times I felt like they were talking about me and us, but I’ve long come to terms with the reality of living with a serious disease. I follow that up with: I have these incredibly serious people working on controlling, and ultimately, curing it! That gives me hope, and that’s what keeps me going.
I’d also like to reiterate another mantra of mine here; see a Multiple Myeloma (MM) Specialist—it really matters!
Okay, Days 2 & 3 Quick Synopsis
Dara, Dara, Dara, Isa!
It is a big deal when a treatment changes the standard of care, and the anti-CD38 antibodies have done just that! Quadruplet therapy as a standard of care in induction therapy has shown amazing results! Even more exciting? Darzalex (daratumumab) has also been shown to prolong progression-free survival (PFS) when used in maintenance therapy. But…wait…there’s more!
Dara is showing incredible promise in high-risk smoldering multiple myeloma (HR SMM). And although Dara took up a lot of space, Sarclisa (isatuximab) showed promising results in induction therapy as well! Isa “might” change the microenvironment, which “might” slow down the rate of progression. It will be interesting to see if this theory plays out and how it plays out!
Next up: Bispecific Antibodies!
Tecvayli (teclistamab) took the center stage in a phase two study, showing promise in induction therapy as both a safe and highly effective treatment. On to phase 3, but it looks very promising. All evaluable patients achieved Minimal Residual Disease (MRD) negativity during maintenance. Patient note: Here’s where the hope keeps sneaking back in!!
Teclistamab is also being looked at in maintenance therapy and early results are positive as well as relapsed/refractory multiple myeloma (RRMM). Elrexfio (elranatamab), Kyprolis (carfilzomib) with dexamethasone are being studied as well.
SO much in the pipeline for Bispecific Antibodies! AND…as if that weren’t enough a bispecific antibody with a new target, Cevostamab is being studied in a phase one clinical trial in heavily pretreated patients and has shown meaningful activity and manageable safety in this patient population at the 160mg TD level given once every 3 weeks.
Studies with Talvey (talquetamab) and Blenrep (belantamab mafodotin) are also showing promise. Though they are sometimes considered harder to tolerate due to the negative side effects, there’s good news here: With adjustments in timing and dosage, these treatments are still effective in managing disease while keeping side effects under control.
New on the scene is Etentamig (also known as ABBV-383), a monthly dosed bispecific antibody. Early studies are promising, and it’s definitely one to watch. I personally was intrigued by its binding domain and its potential to mitigate cytokine release syndrome (CRS) More to come!
Smoldering Multiple Myeloma (SMM): New Hope on the Horizon
When a person has smoldering multiple myeloma and their myeloma is growing, doctors often consider this a “watch and wait” situation. This can be stressful and anxiety-inducing for patients, but the AQUILA study offers hope. It shows that treatment with Dara can extend time before active treatment is required in the high-risk SMM population.
Frailty
Research was presented that looked into the following: reduced dosing, decreased dexamethasone, and clinical trials including older patients. More to come on that, but I will say Darzalex (daratumumab), Revlimid (lenalidomide), or DR outperformed Revilimid (Lenalidomide) and dexamethasone (Rd) in the frail population…down with Dex!!
I’ll stop here for now with the promise to return and further clarify. I hope to share more information once I stop long enough to look at my notes and absorb the immense amount of information I took in over the past three to four days! This is by NO MEANS a comprehensive review; it’s just what caught my attention. Again, I remind all who are reading, this is the takeaway from me…a humble fellow MM patient, and it is how I personally understood the information presented! I hope it gives you a good starting point to delve deeper into the information yourself and discuss what you find with your care team.
It’s exciting to see all this research across the spectrum of treatment lines. It is a non-ending quest for better, safer, and more effective treatment of MM. I was humbled and honored to be a part of the IMF team, and this nerd can’t wait to look at a few of the presentations I did not get to attend! I did have a focus on High-Risk Multiple Myeloma (HRMM), but I did not find much discussion on this. Yet, many studies did include high-risk patients. I will delve deeper in the coming days and share what I find.
That’s it for now! I’ll be back soon with a more detailed post on what I’ve learned from ASH. Thanks for following along and remember: There is always hope! Stay strong, keep fighting, and always reach out to your specialist and team with any questions you may have! They are working every day for us!
HOPE
Hardworking MM specialists and oncologists.
Optimism SO much research for newly diagnosed and those exposed to many lines.
Patients…the center of it all!
Energy! That is what I saw most at ASH an uncontainable energy to do more, know more, help more!
Dec 8, 2024 | Barbara Davis
Regarding sequencing of CAR T: Prior High-dose melphalan (HDM) and stem cell transplant was associated with lower progression-free survival (PFS), but it does not seem to impact overall survival (OS). A question from Dr. Banerjee (MM celebrity), ”Would collecting stem cells and T-cells before transplant fix this problem?”
Hopefully, a study will be conducted to address this.
One of the big new studies by Dr. Banerjee was looking to see if our least favorite lab test, the twenty-four-hour urine, is still needed in light of better testing. The answer is NO! (with several caveats). It is still needed at initial diagnosis or if Bence-Jones proteinuria is the only marker of disease. The hope is that this new recommendation will be adopted by IMWG in the near future. I plan to make this a non-negotiable plan with my doctor starting now!
A special kind of session has been added to ASH, the Health Equity Studio Program, to address Diversity, Equity and Inclusion (DEI) in the healthcare field. The presenter talked about the very complicated issues for undocumented immigrants and mixed-status families. I’m proud to live in a state (MN) that has passed a law allowing undocumented immigrants to enroll in MinnesotaCare. Some states deport ill patients to other countries where they may not get the care they need. Philadelphia has outlawed this practice, showing that change can happen on the local level.
For newly diagnosed patients there are many choices and many questions. Dr. Shaji Kumar says that while four drugs (quads) show improved PFS, a patient’s frailty and tolerance may affect the choice. Drug maintenance with Revlimid (lenalidomide) and dexamethasone (len/Dex) is recommended, yet it is better if both drugs’ doses are reduced.
A presentation about transplantation says that it’s still preferable to chemo alone. I can’t help but wonder when it will be phased out in preference for BsAbs and CAR T.
We all know what MGUS is, but I learned about 2 new ones, MGCS and MGRS, clinical significance, and renal significance.
Dec 8, 2024 | Terry Glassman
We started our day at 5:30 am by hopping on a shuttle to head over to the International Myeloma Working Group Breakfast sponsored by the IMF. I must say it was an extraordinary experience to be in the room with all the top Myeloma Doctors, listening to their research (which I can’t tell you about or I’d have to kill you…not really, that’s from a movie…but I can’t tell you)! What I can tell you is that this is a VERY dedicated group of physicians, and they are working hard to advance treatment in multiple myeloma (MM) for us all. We are in VERY GOOD hands! I’ve listened to so many of these specialists in webinars that I felt like I knew them! I had to remind myself that I indeed did not know them, but I thanked whomever I did talk to for the work they do! Some pretty exciting stuff in the pipeline: some of it will be reported on in the coming days, so I’ll try to get that to you all.
As for reporting on the actual conference today, I am going to leave that to a future blog so I can do it justice—but here are some key takeaways:
- Darzalex (daratumumab) is awesome, and treating the newly diagnosed with quadruplets is the way to go!
- Twenty-four-hour urine collections are very useful in initial screening, but they may not be necessary in later assessments.
- There were a few abstracts speaking to quicker assessments in relapse, which one would hope will translate into quicker treatment of the patient.
- There was an interesting abstract on the Influenza vaccine; it might benefit MM patients to do a three-dose series rather than the one vaccine, especially if you are on a CD38 monoclonal antibody like Darzalex (daratumumab).
- IVIG (Intravenous immunoglobulin) reduces infections in patients treated with BCMA (B-cell maturation antigen) bispecific antibodies.
- There were a few abstracts on minimal residual disease (MRD) testing, but I’ll write more on that next time!
- And, the last abstract talked about measuring serum BCMA levels in non-secretory disease to monitor for disease progression—it showed some promising results.
That’s my abridged synopsis of day one. Please read this understanding that I am a myeloma patient telling you what I personally understood from all I listened to. I’ll write in a little more detail in the coming days. All in all, a GREAT experience and very heartening and comforting to see all that is being done to enhance the treatment of multiple myeloma patients!
One word: H O P E !!!
@TerryGlassman
Dec 7, 2024 | Linda Huguelet
Friday evening (Eastern time), I attended one of the best symposiums I’ve seen in my 12 years of attending the American Society of Hematology (ASH) Annual Meeting. Sagar Lonial, MD moderated a panel of elite myeloma specialists through five modules of discussion. The panel included Professor Philippe Moreau, MD; Robert Z Orlowski, MD, PhD; Noopur Raje, MD; Paul G. Richardson, MD. The discussion also included real-world clinical questions from six community-based hematologists.
The Modules ran the spectrum from newly diagnosed to what the future holds. The modules were Management of Newly Diagnosed Multiple Myeloma (MM), Integration of Novel Therapies into the Management of Relapsed/Refractory MM, Chimeric Antigen Receptor (CAR) T-Cell Therapy for MM, Bispecific Antibodies for the Treatment of MM, and Other Novel Agents and Strategies Under Investigation for MM.
Each panelist led one of the modules which sparked good conversation and sometimes debate among the group. I can’t include all the items that caught my attention from the two-hour event, but a few key takeaways for me included:
- Quad therapies of Darzalex (daratumumab), Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone; or Sarclisa (isatuximab), Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone definitely show benefit and no need to avoid adding the monoclonal antibody to the tried and true Revlimid, Velcade, dex induction therapy. They produce increased response and increased minimal residual disease (MRD) negativity.
- The use of autologous stem cell transplant (ASCT) did not have 100% endorsement from the panelists. Drs. Lonial, Moreau, and Raje continue to see value, while Dr. Orlowski did not favor using it upfront and Dr. Richardson was undecided. What does the future hold for ASCT? Will CAR T-cell therapy take its place in the future? I’ll be listening closely in the abstracts for more information on this topic.
- The use of Xpovio (Selinexor) got favorable reviews from the panel when it was used at lower doses than originally prescribed. Its unique mechanism of action provides a new way to attack myeloma. I used this drug as part of my bridging therapy before my CAR T-cell therapy in 2023. I was wisely advised by the late Jack Aiello on the dosage—which concurs with what was presented in the symposium, and I had a very positive experience with this treatment.
- There was consensus that PET/CT is advised post-CAR T-cell therapy to monitor for extramedullary disease. I questioned the need for this in my last visit with Dr. Lonial and this reason, which was also confirmed by my local hematologist, convinced me of the true need. I have this scheduled for two weeks from now.
- Blenrep (belantamab mafodotin)—the antibody drug conjugate—will be back in the arsenal of FDA-approved treatments. I’ll be looking for additional data from the DREAMM 7 and DREAMM 8 studies over the next couple of days. Given at reduced dosing and spread out over as much as 8-12 weeks, this is showing efficacy without the previously reported difficult ocular side effects.
- Iberdomide and Mezigdomide, which are advances of immunomodulatory agents like Revlimid and Pomalyst, show great promise. There was a discussion that they may even replace Revlimid in the induction therapy regimen in the future.
I’m excited to get started in the Annual Meeting which starts virtually for me this afternoon. Please check out the blogs and tweets on Twitter (X) of the entire ASH 24 team throughout the conference to stay up-to-date on all the promising advancements.
Linda Huguelet, Chattanooga Multiple Myeloma Networking Group
@LindaMYELOMA
