Monday afternoon at ASH found me listening to an abstract by Nora Grieb. It was a study from the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy. Autologous stem cell transplantation (ASCT) following high-dose chemotherapy is a standard treatment for newly diagnosed multiple myeloma patients. Tandem transplantation, involving two ASCTs, is generally recommended for those who do not achieve at least a very good partial response (VGPR) after the first ASCT, or those with high-risk features. The reason I found this interesting was that I faced a decision of single or tandem transplant in 2007.
The results of the study got very detailed for me but what I understood was important for the patient. Out of 12,763 patients, 6,581 underwent a single ASCT and 4,027 underwent tandem ASCT. Patients who received a second ASCT or an allogeneic transplant after the first six months of the initial ASCT were considered part of the single ASCT group. There was a shift in transplantation practices over time, with tandem ASCT becoming less common: 47.4% before 2008 versus 25.7% in 2017-2021. Moreover, the percentage of patients in complete remission (CR) post-induction therapy increased over time (7.4% between 1998-2007 versus 13% after 2017), as did the percentage achieving CR after the first ASCT (20.5% before 2008 vs. 32.3% after 2017).
When comparing single and tandem ASCTs, no significant difference in OS or EFS was observed for patients who achieved CR after the first transplant. However, patients who did not achieve CR after the first ASCT experienced a significant OS benefit with tandem ASCT. This benefit was also evident in patients who did not reach CR after induction therapy. Interestingly, there was no significant difference in OS or EFS for patients who transitioned from non-CR to CR after the first ASCT. The study analyzed the impact of the International Staging System (ISS) and renal impairment on outcomes. ISS stage III was significantly associated with worse OS for patients with renal impairment. Notably, patients with ISS stage I and no renal impairment showed a significant benefit in OS from tandem ASCT, while those with ISS stage III and renal impairment fared better with single ASCT.
Conclusion
Don’t ask me to explain much more than my current thoughts but the study shows that patients who did not achieve CR after induction therapy or the first ASCT benefited from a second ASCT. However, patients with ISS stage III and renal impairment had poorer outcomes, and in these cases, single ASCT was associated with better survival. What I liked about the study was these findings suggest a need for tailored approaches based on patient characteristics to optimize treatment strategies for NDMM patients. And I believe that is a good thing for the patient.
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!
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.
