ASH Day 2: Which CAR to Hitch a Ride with?

ASH Day 2: Which CAR to Hitch a Ride with?

December 12, 2021 – Today began with watching a few presentations that focused on the epidemiology of myeloma patients. For example, abstract 400 examined COVID-19 vaccine effectiveness for multiple myeloma (MM) patients associated with the VA. They examined nearly 7,000 MM patients and compared COVID-19 results with vaccinated and unvaccinated patients, as well as compared these with non-MM patients. Not surprisingly, they concluded that vaccines were an effective strategy for preventing COVID-19, but less so for MM patients.

Abstract 402 examined racial and ethnic differences in MM patients. The presenter, Dr. Nancy Gillis (Moffitt Cancer Center – Florida) remarked that “Blacks are getting one-half the benefit of improved survival outcomes compared with whites. However, similar access to care results in similar outcomes.” As a society, we need to do more to accrue a diverse population in our clinical trials and then provide better access to new treatments.

I always appreciate it when negative trial results are presented. These are trials where the suspected benefit hypothesis is not met.  Abstract 466 compared Ninlaro® (ixazomib) added to Revlimid® (lenalidomide) + dexamethasone (IRd) maintenance versus (Rd) alone and concluded that the Ixa arm did not result in improved progression free survival (PFS).  And abstract 486 concluded that the addition of Empliciti® (elotuzumab) to Revlimid, Velcade® (bortezomib), and dex (ERVd) induction/consolidation and Rev maintenance did not result in improved PFS or overall survival (OS).

Other abstracts showed the benefit of adding either Darzalex® (daratumumab) or Sarclisa® (isatuximab) (both CD-38 monoclonal antibodies) provides benefit when considering outcomes such as responses, minimal residual disease (MRD) rates, PFS, and or OS. Example include Abstracts 463 (Isa + RVd induction), 464 (dara + IxRd induction), and 465 (dara + CyBorD + Rev (5 drugs!) for ultra high-risk MM).

Another important study, Abstract 467 examined the impact of chromosome 1 gain (3 copies), amplification (>3 copies) and deletion, conferring inferior PFS compared with standard risk patients. Kyprolis® (carfilzomib), Revlimid, and dex (KRd) may overcome negative OS for gain1 and del1 but not necessarily amp1, however more follow-up needs to be done for this particular mutation.

And speaking of chromosomes, 17p deletion is long-considered to be a high-risk factor. But how is the clone size (17del seen in >60% plasma cells) impacted by a tandem transplant?  Abstract 460 demonstrated tandem transplant compared with a single transplant improves outcomes but clone >60% may negatively impact outcomes. However, there were a couple of audience questions about biased results, such as tandem patients being more fit than single transplant patients.

I want to now share what I consider today’s most impactful presentations. All of the CAR T’s presented below have an additional focus of lengthening the persistence (survival) of the CAR T cells in order to increase PFS times.

CAR’s and more

  • CT103A CAR T from China demonstrated (N=79) 95% ORR with 58% CR with mPFS of 25 months.  The first enrolled patient is still in stringent complete remission (sCR) for 34 months. And for 13 patients who had previous CAR T, ORR was 77% and CR 39%.  [547]
  • bb21217 CAR T for N=72 included 40% HR and 22% EMD patients. Results include 69% ORR (inc 28% CR) and mDOR of 2 yrs. [548]
  • CARTITUDE CAR T updated results after 2 yrs follow-up for N=97. ORR 98%, CR 83%; 2-yr PFS and OS were 61% and 74% respectively and even higher for those with sustained MRD-. [549]
  • ARI0002h CAR T appears unique because some of a patient’s CAR T cells are given up front and then a booster dose is subsequently given. For N=30, ORR=100 and CR=60% and the mPFS is estimated to be 18 months. 
  • Master Trial: Dara-KRd -> SCT -> D-KRd -> D-KRd -> R maintenance. MRD is tested after each treatment and 2 successive MRD- at 10-5 results moves the patient into a MRD-SURE category to stop treatment (observation only) with continued MRD surveillance. Results were presented for SR, HR and UltraHR (>1 HR factor) patients. 2-yr PFS and OS were in the 90%+ for SR and HR but only 58% and 76% respectively for UHR pts. And 84 pts (72%) achieve MRD-SURE. [481]
  • In abstract 551, an oral Gamma Secretase Inhibitor to increase BCMA expression may be used in the future with BCMA-directed therapies.

That’s it for today.  Tomorrow’s sessions include IMWG Conference Series from ASH 2021. IMF Chairman Dr. Brian G.M. Durie, Dr. Maria V. Mateos (University of Salamanca — Salamanca, Spain), Dr. Thomas Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA) and MM Nurse extraordinaire Beth Faiman PhD, RN, MSN, APRN-BC, AOCN (Cleveland Clinic Taussig Cancer Institute — Cleveland, Ohio) distill, debate, and discuss the latest news and trends in the treatment of multiple myeloma from this 63rd Annual ASH Meeting. Check out the IMF website for replays.

Be your own best patient advocate.

— Jack Aiello, on Twitter @JackMAiello

Day 3:  Focusing on Priorities Amid All the Details —Time to Reset!

Day 3: Focusing on Priorities Amid All the Details —Time to Reset!

During yesterday’s blog, I focused much on details of studies, trying to absorb as much of the scientific data as possible. As a nurse who hasn’t had formal training on data collection and research, it can be very easy to get lost in that data. I found myself feeling like I was in the middle of a tornado, spinning around in circles, and grabbing ahold of whatever I could, information-wise. 

ASH is intense! 879 Abstracts at ASH 2021 focused on multiple myeloma — that’s a TON of information to soak in in 4 days! I decided to take a step back and refocus on my goal. I took advantage of some of the mindfulness exhibits available to try to calm the storm! This storm is not a negative one, I want to be clear on that. The information storm that I speak of is simply a lot of information in a short time. I do appreciate the ability to view the abstracts for the rest of the month and absorb more information, including details, from each one. 

My personal goal for attending ASH this year was to be able to communicate information from the research back to my support group members and their care partners. It seemed like a simple goal when I made it, but when given this amount of information, it is so easy to get stuck in the weeds about what parts to report on, what details are important. 

What is REAL LIFE info that patients will benefit from? I have to admit, sitting in front of my laptop for 10 hours straight, feverishly taking notes, snapping screenshots, looking up keywords, making outlines, and trying not to miss a word of this important information being shared was OVERWHELMING! I started to reevaluate my strategy for moving through the rest of the conference, and to be real with myself! I’m not going to catch every word or understand every definition or statistic. I’m not going to remember all the data and be able to recite it word for word. That’s not realistic, nor attainable!

My major takeaways from Sunday’s oral and poster presentations: 

• I appreciate, more than words can say, myeloma specialists who can present incredibly technical information in a way that is understandable! Drs. Luciano Costa (O’Neal Comprehensive Cancer Cen ter University of Alabama — Birmingham, AL) and Thomas Martin (UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, CA) are two of the best! Truly personable, funny, and down-to-earth enough to be able to simplify some incredibly difficult information! Thank you, from patients and nurses alike! 

• It is important to acknowledge the financial disparities between the US and the rest of the world when it comes to drug costs and availability. We have to do better so that patients can have access to proven therapies. 

• Ciltacabtagene autoleuce (cilta-cel) is EXCITING! Updates to 24-month progression free survival and overall survival data were presented and look incredibly positive. With an updated Prescription Drug User Fee Act (PDUFA) date in February 2022, there is much anticipation for this therapy for at least triple refractory patients. Hopeful that the manufacturing slot availability will be able to support the almost assured demand!

• I overheard a comment made when discussing the diversity profile of a study group of a particular clinical trial that stated that the 17% African American participation in this trial was “impressive and encouraging.” This makes me sad when less than 1/5 of the study population being minority is encouraging! We need to do better with recruiting more minority subjects into myeloma clinical trials. With a disease that clearly has a great impact on the African American population, we need to do better getting an appropriately diverse study selection when researching and learning more about it!

Share Hope. Education is Power. Stay excited and motivated for the future!

Becky Bosley, on Twitter @MidAtlanticMSG 

The Words Are HOPE and GRATITUDE

The Words Are HOPE and GRATITUDE

As I reflect on the end of this first official day of the ASH Conference, I must say that I feel HOPE and GRATITUDE. I pored over the very complicated ASH Agenda. The IMF-SGL team of veterans and newbies is well-organized and so generous with sharing lessons, hints, and strategies to get the most out of this opportunity.

My focus was on studying the agenda and setting my personal ASH schedule, listening to pre-recorded sessions, and participating in the day’s live educational sessions. I came to this meeting hoping to see evidence of health equity and translational research from “bench to bedside to curbside.”

It is stated throughout the agenda that each program at ASH is expected to demonstrate diversity. In every part of the program, there was an expressed intentional focus on Diversity, Equity, and Inclusion (DEI). There is an Anti-racism Studio with presentations each year to raise awareness and encourage a thoughtful approach to race (ism) in medicine.

Props to Dr. Deepika Darbari (Children’s National Hospital, George Washington University School of Medicine and Health Sciences), who received an ASH award for leadership in diversity. She is engaged in the mentorship and training of underrepresented minority researchers and in advancing the care for underrepresented patient populations, primarily individuals living with sickle cell disease (SCD).

While at Howard University, an HBCU, she saw firsthand many disparity issues, such as inadequate funding, limited treatment options, and biases and stigma. She also learned about barriers to career development that minority students faced. There is hope that a new generation of scientists will bring their unique talents to the research agenda. They can use their unique perspectives to ask and answer questions that can help to unravel the mysteries of myeloma.

My educational sessions were a dive into the deep end of the pool, with a great harbinger of things to come. “High-Risk Multiple Myeloma and Treatment at Relapse” was the topic of the pre-recorded session from a Spain presenter. The live session was a series of case studies for which five international physician-scientist experts from France, Spain, and the U.S. and the audience responded to Zoom polls on the best course/s of treatment.

The session was aptly entitled “Adapting Clinical Practice to a Rapidly Changing Therapeutic Landscape.” This is one of my favorite types of sessions. It’s a reminder that myeloma is a complex disease that can require a complex response to get it under control. I was reminded of the deep pipeline of ongoing myeloma research and of the need to adapt treatment to the individual, their type of myeloma, and their lifestyle.

The “HOPE” is that there are approved treatment options or clinical trials for almost every scenario. The need for continuous education for multiple myeloma specialists, community oncologists, and primary care doctors is crystal clear. I HOPE one day that the protocol for any physician who treats myeloma is that they schedule a telemedicine conference that includes the patient.

These specialists respectfully disagreed on several points, but we were able to hear and appreciate their reasons for the divergence. It was like a Masterclass for the physicians/clinicians in the audience. We could see from the polls their votes on the appropriate regimen – pre-and post-presentation. In some cases, there was a dramatic change in their opinions.

In addition to the regimen, the presenters did not shy away from the expense related to some treatments versus others and the availability of certain drugs. Insurers can sometimes determine whether a particular treatment will be approved. Some prerequisites for regimens make them inaccessible to entire populations of myeloma patients.

So, there is much to be about. This first day heightens my HOPE for a cure. I am eternally GRATEFUL for the curious and determined researchers, physicians, providers, patients, caregivers, and sponsors, and others who together move us towards a cure.

Gail G. McCray, on Twitter: @IMFgailMyeloma

Myeloma researchers and experts from around the world present and discuss case studies.

Pre-ASH Blog: New Myeloma Science at ASH: Health Equity at the Curbside

Pre-ASH Blog: New Myeloma Science at ASH: Health Equity at the Curbside

Well, everyone. 

We are in the week leading up to a major annual international conference, the American Society Hematology (ASH). During this meeting, bench and clinical myeloma research from all over the world will be presented and discussed.  

I am excited, humbled, and fearful at the same time. I am humbled at this tremendous opportunity afforded to me by the IMF. I would love to see and hear everything over the 4 official days of the meeting, but that would be impossible. I heard that there are over 600 people who will share their research on multiple myeloma. I’m studying the agenda and trying to decide when and where to go, and whom to hear. It’s all virtual, so it should be easier, but not for me. There are so many wonderful and different choices!  

Have you ever heard the phrase, “from bench to bedside?” It’s all about taking laboratory research from the laboratory to hospitals and clinics. The more important phrase for me is: “from bench to bedside to curbside.” I will spend more of my time in the translational research area, where the research reaches the “end-user” – the patient in the community…at home… at the curbside. 

Of course, I am eager to hear about the new scientific advances in myeloma. I am also interested in what scientists have to say about health equity – or if, in the post- George Floyd era, if there is any mention of racism in medicine and how that might impact effectiveness of the delivery of vital research.  

Is the best science available to everyone? This is a question raised by some who might hesitate to participate in the clinical trials. Will the best of the research be available to everyone in an equitable way – regardless of age, race/ethnicity, gender, or income level? These are some of the thoughts that will take me into the preparation and the first days of this incredible experience. 

Gail McCray  

Southside Atlanta, GA 

 Gail McCray, on Twitter: @IMFgailMYELOMA