What another great experience for myself and our Myeloma Voices Team at ASH (American Society of Hematology). San Diego is such a nice place to visit, and I really enjoyed being with our in-person team as we attended the sessions together, discussed what we had heard, and dined together. We all come from slightly different backgrounds and myeloma journeys, but we all have one thing in common: The hope of finding a cure for multiple myeloma (MM).
There were a variety of abstracts that caught my eye. The first one was Saturday morning with the study that showed previous treatment with high-dose melphalan (HDM) and an autologous stem cell transplant (ASCT) adversely impacts progression-free survival (PFS) in BCMA-directed CAR-T therapy. Their findings showed that having a prior HDM/ASCT is associated with a shorter PFS to a BCMA CAR-T, but it did not impact the response rate or overall survival (OS). Which CAR-T product you received made a difference.
Ide-cel (Abecma) showed a lower complete response (CR) and a shorter PFS. But, there was no difference between the 2 groups (ASCT or no ASCT) with Cilta-cel (Carvykti) or Anito-cel (still in clinical trials). Will these findings make a difference in the future of ASCT or help to decide which CAR-T therapy is best for which patient? Further clinical trials of CAR-T therapy for newly diagnosed multiple myeloma (NDMM) patients could provide further insights into this question.
The next abstract presented by Dr. Rahul Banerjee (Fred Hutchison Cancer Center), stated that the infamous twenty-four-hour urine testing does not add value to the assessments of MM patients. Real-world analysis showed that only 28% of U.S. patients with MM had any twenty-four-hour urine testing done at diagnosis. In his study, only 1.1% of the analyzed patients had different responses between traditional and urine-free response criteria. The 24-hour urine testing is still essential in screening patients with MGRS (monoclonal gammopathy of renal significance), for example, having AL amyloidosis. But Dr. Banerjee is hoping to have the International Myeloma Working Group (IMWG) place less emphasis on the twenty-four-hour urine requirements in future revised response criteria.
An interesting study was presented by Dr. Craig Hofmeister with the Winship Cancer Institute of Emory University in Atlanta, GA. He presented a trial that demonstrated a three-dose flu vaccine series improves protection over a single flu shot. This was especially true for patients, like myself, who are on Darzalex (daratumamab). The study showed that a single flu vaccine’s seroprotection wanes by the end of the flu season. Giving the vaccine at week 1, week 9, and week 17 improves protection, especially for patients on daratumamab.
Of course, there are obstacles to this in the real-world. It can be hard to convince patients to get 1 flu vaccine, much less 3 over the flu season. And getting insurance to pay for 3 would be difficult, as would asking patients to pay out-of-pocket for 2 of the 3 vaccines. It is still an interesting study, given the older population of myeloma patients, and the propensity for serious illness from getting the flu.
Every year at ASH my takeaway is how many patients are participating in clinical trials around the world. If it were not for these patients, we would not have new myeloma treatments. At the end of every abstract presented, the doctor thanked the patients and their families for participating. I have not been able to participate in a trial yet, but it is my hope that I may be able to give back and participate one day. There is so much more, and I hope you read the blogs of my fellow Myeloma Voices Team. And join us on January 8th as we discuss the latest myeloma updates from ASH 2024.
This was my first ASH Conference, and my expectations were exceeded.
The volume of oral and poster abstracts was overwhelming. To get through just the multiple myeloma (MM) information presented would have taken more than the three days that I was in attendance. An incredible amount of work has been done in preparation for this conference.
Many of the top doctors in the world either presented or sat through the abstracts and asked questions. The commitment to learning and collaboration was on full display throughout the conference.
The number of treatments approved and now in use has accelerated over the previous several years, and this year was no exception. Moving newer therapies to earlier lines is a big theme, with Datatumamab and Teclistamab taking center stage.
I am not going to highlight or summarize treatments. More qualified people are already hosting events where the information is readily available. For many of us with MM, this ASH was great. Better treatments are available, and more are on the way.
Not so fast…
Infections are the leading cause of mortality in patients with MM, occurring in 22 to 45 percent of patients. This statement supports the case for IVRT in one of the presentations. In another presentation, the speaker stated fifty percent of patients do not make it to the following line of therapy for various reasons. I have repeatedly heard this from doctors since being diagnosed in 2020.
This information is glaring and alarming. As we move into the era of CAR T and Bi-specifics used in earlier lines, we should assume infections will rise. More patients will learn about and require IVRT much earlier than ever before. Even without new novel therapies, MM patients need to be proactive in seeking help earlier if they suspect they are sick.
If you are not feeling well, call your doctor. Over my four years of living with MM, I’ve never had a nurse tell me I should have waited to call when I did not feel well, although I have heard a few times I should have called earlier.
I am grateful for the ongoing work done by doctors and researchers to develop better treatments and, one day, a cure for MM. Until then, I hope we all get to the subsequent line of therapy if and when it is needed.
After yesterday’s abstract sessions, I think I have more questions than answers. Not exactly what I was hoping for, but questions do lead to more investigation and knowledge. There was a lot of discussion about the use of TECVAYLI (teclistamab). This bi-specific antibody is currently used only in later lines of therapy, but trials are now looking at it as part of induction and maintenance therapy.
This constant review of combinations may lead to even deeper initial responses, which is certainly the goal, so it’s certainly worth exploring. But the current induction standard of care quadruplet of Darzalex (daratumumab), Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone seems so effective for most patients that I continue to question whether you would not save bi-specifics for later use in your myeloma treatment arsenal.
Treatment sequencing is an ever-perplexing issue – somewhat of a blessing and a curse. A blessing because that means we have many more options to select from and a curse because it is ever more difficult to select the correct sequence as well as to understand how sequencing can be tailored to each patient’s situation.
Some of today’s abstracts will provide some insight into real-world data on how bi-specifics and CAR T-cell therapy are performing, which I am looking forward to.
I am also very excited about the Facebook live session this evening featuring Dr. Joseph R. Mikhael (“Dr. Joe”) and his thoughts on the conference highlights and he will be taking questions as well. It may be late for my group on Eastern time, but it will be worth it!
This is my fourth year attending the American Society of Hematology (ASH) meeting virtually. While I miss seeing my myeloma support group leader faMMily in person, there are some nice perks to attending ASH virtually. First, I can easily pop between sessions without having to race through the conference halls. This is a big plus because I always have trouble choosing between myeloma sessions focused on scientific innovations, clinical trials, or health outcomes and health equity. I can spend my breaks viewing talks that I miss rather than hurrying to the next location. A second related perk is that I can sit in my comfy chair. As a myeloma patient with bone involvement, I still have considerable bone pain at times, even though I’m in remission, and those conference chairs are not nearly as comfortable as sitting in a recliner with a heating pad against my back. Probably the best part of attending ASH virtually each year though is having Miss Lilypad on my lap.
We adopted Lili and her siblings Leo and Ellie a year after my autologous stem cell transplant at the prompting of my youngest daughter Ellie. Indeed, that’s how we ended up adopting 3 kittens; we almost left Ellie the Cat behind, not knowing that we had chosen to adopt her two siblings. Ellie the cat is now affectionately called Grumps and Leo is called Lenny or Nerd, and Lili has become Miss Lilypad. The nicknames suit them all so well. There is nothing that Miss Lilypad loves more than plopping down on a lap for some cuddles whenever a lap is available. That’s why she loves ASH so much, 8-12 hours of constant lap time – what can be better!
It’s a little bit challenging for me to navigate my laptop and take notes with Miss Lilypad on my lap, but she’s the boss, so I’m figuring it out. Turns out that Miss Lilypad is also quite creative and enjoys helping me write haikus about the ASH experience. One of her #ASHaiku X posts even made it into the Saturday evening ASH News Daily!
The first session that Miss Lilypad and I attended together on Saturday was a session entitled, “Multiple Myeloma: Clinical and Epidemiological: Decluttering Responses and Dynamic Risk: How Can We Improve Prognostication in Multiple Myeloma?” The entire session was excellent, but two talks particularly caught our attention. First, Dr. Joshua Gustine, MD from Massachusetts General Hospital in Boston, MA discussed how previous autologous stem cell transplant (ASCT) can affect length of progression-free survival (PFS) after CAR T-cell therapy. The results presented showed that Ide-cel, but not Cilta-cel or Anito-cel, exhibited a decreased PFS in patients who had a previous ASCT compared to those who did not. While the reasons for these differences are not yet clear, it’s another important consideration for patients to discuss with their doctor when deciding on next treatments. Miss Lilypad just hopes the CAR T-cell therapy is still off in the future for me because she thinks I have the best lap in the family as I’m the most likely to stay seated for long periods of time. The other talk in this session that caught our attention was a talk by Dr. Rahul Banerjee, MD, FACP, from the University of Fred Hutchinson Cancer Center in Seattle, WA. Dr. Banerjee made a case for eliminating the twenty-four-hour urine collection as a method for following myeloma status in clinical trials as it is a barrier for patients. While twenty-four-hour urine collection remains important at diagnosis and under some unique patient circumstances, such as concurrent amyloidosis or when there is no other clear biomarker of disease status, most patients are celebrating the results of this study because the twenty-four-hour urine collection can be quite a pain. Miss Lilypad and I were inspired to write another ASH haiku about this talk as we reflected on the years with pee jugs in the fridge when the kids were in high school, and Dr. Banerjee even gave it a shout out on X.
Miss Lilypad and I also attended an afternoon (evening on the east coast) scientific session entitled, “Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Understanding and Improving TCE and CAR-T Cell Therapies for Plasma Cell Disorders.” This session covered lots of cool scientific talks that addressed how to improve outcomes for immunotherapies like CarT cell therapies and bispecific antibodies. As a scientist and patient, I love these talks, and I find it encouraging that so many amazing researchers are working hard to understand the challenges of resistance and loss of PFS with current immunotherapies due to issues such as the role of the tumor microenvironment in T cell activation and exhaustion. Miss Lilypad likes these talks because many of these studies are done using mouse models. She fell asleep on my lap during the session, dreaming of mice, so I’ll save reporting on the science of these talks for my next blog since there are more exciting science talks in the days ahead. Good night Lilypad!
The first day is kind of a beginner’s day, with a number of Continuing Medical Education (CME) courses/presentations. I went to two: The first was Championing the Care of Relapsed/Refractory Multiple Myeloma: Practical Strategies to Integrate Bispecific Antibodies, and it was presented by Drs. Ajai Chari and Amitra Krishnan. Here are some of its key points:
Heavily pretreated relapsed/refractory (R/R) patients will continue to fail more and more drugs
In the HORIZON study, there were three bispecific antibodies: linvoseltamab, Tecvayli (teclistamab), and Talvey (talquetamab) used, each in a different arm of the study. Patients were heavily pretreated relapsed-treated MM patients, yet, they still each had an overall response rate (ORR) of over 60%
Oral and skin toxicities were higher with talquetamab, but the infection rate was lower. Both doctors agreed that patients must be warned about skin problems. Also dysgeusia (my new favorite word, means abnormal taste), weight loss, and (rarely) cerebellar ataxia (poor muscle coordination).
They discussed how to choose between CAR T-cell therapy and bispecific antibodiess? Timing is very important. Dr. Chari said to consider the time from “brain to vein,” meaning the time when the doctor first thinks about putting a patient into the CAR T list to when the patient’s T cells are reinfused is long. So, the question is can the patient last long enough, or is their disease rapidly progressing? In the latter case, a bispecific antibody would be the better choice.
There’s still much learning to be done about sequencing these new therapies. “More questions than answers,” said Dr. Chari.
Management of key toxicities is extremely important. Clinicians must treat for cytokine release symptoms (CRS) as the first symptom. Also, infection management must be done at first onset, often giving IVIG as soon as treatment is started.
“Bispecific antibodies will become as routine as Darazalex (daratumumab) now,” said Dr. Krishnan.
Bispecifics and other MM drug combos are currently off-label. Phew! It was an interesting discussion, and I was pleased that I understood so much. The next session was a bit harder, but I’ll tackle that report tomorrow. It was about Optimizing CD38 antibody-based triplet regimens for early relapse MM. For my fellow patients, you probably know that early relapse is a signal that your myeloma is showing itself to be high- risk. That sounds scary; and it is scary, but I was also impressed that so much energy is being put into drug development and clinical trials to learn how to successfully treat the high-risk patient.
