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!
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.
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.
