Progress in the Field of Myeloma: the Past, the Present, and the Future
By Dr. Joseph Mikhael, IMF Chief Medical Officer
The pace of drug development and advancement in myeloma in 2024 has been truly unprecedented, with a cascade of drug approvals, innumerable phase III clinical trials, epidemiological studies, scientific discovery, and reductions in health disparities. As I seek to keep the readers of Myeloma Today updated, the list of hot topics seems to never end – and I love it!
FDA approves two new quadruplet therapies
In the last few months, we have seen two different “quadruplet” (4-drug) combinations approved for newly diagnosed multiple myeloma (NDMM). In July, the U.S. Food and Drug Administration (FDA) approved the combination of Darzalex Faspro® (daratumumab hyaluronidase-fihj) + Velcade® (bortezomib) + Revlimid® (lenalidomide) + dexamethasone [DVRd] as initial therapy for patients eligible for transplant. In September, the FDA approved the combination of Sarclisa® (isatuximab-irfc) + Velcade + Revlimid + dexamethasone [Isa-VRd] for patients not eligible for transplant.
The approvals of DVRd and Isa-VRd are important for many reasons. Firstly, what patients are treated with in frontline therapy has a long-term effect as the first remission is usually the longest. Secondly, it validates the complex biology of myeloma, which we can better control with multiple drugs that have different mechanisms of action. Significantly, with response rates well above 90%, I believe this also means that patients with myeloma will live longer and better lives. This brings us ever closer to seeing the vision of the IMF become a reality: a world where every myeloma patient can live life to the fullest, unburdened by the disease.
International Myeloma Society (IMS) meeting
In addition to these important recent approvals, the annual meeting of the International Myeloma Society (IMS) took place in September in Rio de Janeiro, Brazil. The “Who’s Who” of myeloma were present. We discussed the most promising trends of development in myeloma research and clinical practice. In brief, the takeaways include the following:
1. Quadruplet (4-drug) combination therapies in frontline therapy are benefiting more and more patients with myeloma. The overall survival (OS) advantage of quadruplets over triplet (3-drug) combination therapies has been demonstrated in several clinical trials. Quadruplets are here to stay – for both transplant-eligible and transplant-ineligible patients.
2. The dosing of drugs is absolutely critical, especially in older or frail patients. For example, the dose of dexamethasone must be chosen carefully and may be tapered, Velcade can be given once-weekly and for limited duration, lower doses of Revlimid may be advisable.
3. Minimal residual disease (MRD) is being used as a guided approach to myeloma therapy. This is very important as we want to use this tool effectively to optimize therapy. The potential to shorten the duration of therapies is very attractive. However, this tool is still not ready for use in the clinic as we need more evidence from ongoing research.
4. Real world experience with CAR T-cell therapies in myeloma is demonstrating even more impressive outcomes in early relapse. It is clear that using CAR T in earlier-line therapy yields greater efficacy than in later-line therapy.
5. The many new approaches to immunotherapy in myeloma include “allo-CAR T-cell therapy” where T cells are collected from healthy donors and not from myeloma patients.
6. More options for dual maintenance therapy include adding Darzalex to Revlimid. There is a strong trend to deepen response in early maintenance. Data is emerging to consider stopping Revlimid based on MRD status.
7. The re-introduction of belantamab mafodotin as a treatment agent for patients with myeloma. It is a highly effective agent, proving itself in a triplet vs. triplet clinical trial. It is easy to administer. We hope to have it back in the clinic in 2025.
IMF Scientific Advisory Board
The IMF Scientific Advisory Board (SAB) is comprised of world-renowned myeloma researchers who have each made a profound contribution to improving outcomes for patients with myeloma, to driving the advances in myeloma research, and to supporting the mission and the vision of the IMF. To learn more about the newly assembled SAB, read the message from Yelak Biru on page 2 of this edition of Myeloma Today.
The SAB is part of what I often describe as the IMF’s superpower, the 3 Cs – the IMF is Collaborative, Creative, and Comprehensive. We are employ ing all three Cs as we bring together these myeloma experts to advance the IMF mission to cure myeloma and to fulfill the IMF vision of a world where every myeloma patient can live life to the fullest, unburdened by the disease.
IMF’s international initiatives
In collaboration with myeloma experts from Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay, the IMF recently founded the Latin American Myeloma Network (LAMN). The objective of the LAMN is to accomplish the following in Latin America:
- Supporting the earlier diagnosis of myeloma
- Providing more myeloma education in Spanish and Portuguese
- Increasing access to myeloma therapies
- Generating myeloma data for Latin America
- Conducting clinical trials in Latin America
- Developing and supporting collaborative initiatives across all of Latin America
- Elevating the work of Latin American myeloma researchers within the international scientific myeloma community
The first LAMN Summit was held in Rio de Janeiro, Brazil at the end of the annual meeting of the IMS. Junior investigators from each country presented proposed projects and collaborations for LAMN to assess and consider. Furthermore, LAMN will soon launch its first clinical trial for patients with relapsed myeloma. Many more activities in research, education, and advocacy are in the planning stages. The LAMN initiative of the IMF was inspired by the Asian Myeloma Network (AMN).
Established by the IMF in 2011, the AMN is the first network of its kind in the region, comprised of myeloma experts from China, Hong Kong, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. The AMN provides physician education and has created a unified database to assess the incidence of myeloma in Asia as a basis for establishing region-specific treatment management tools and strategies. The AMN is conducting collaborative clinical trials that enable myeloma patients to gain access to the newest myeloma therapies. The AMN supports patients and care partners throughout Asia with educational materials in local languages. The 2024 AMN Summit took place in October in Seoul, South Korea, and you can read more about it in the Winter edition of Myeloma Today.
IMF’s educational meetings and events
The science of myeloma is advancing at fast-forward speed, and the IMF has the privilege of delivering the critical information about the progress being made to patients and their care partners in real time. One of the greatest joys of my career is making complex concepts accessible and comprehensible to all. This is a key objective of the IMF, as demonstrated by the number and variety of recent educational events for members of the myeloma community.
Truly, there are too many to list here, so I will mention just two of our flagship programs – the Patient & Family Seminar (PFS) and the Regional Community Workshop (RCW).
The PFS and RCW programs together comprise more than 12 in-person and virtual meetings designed to educate, inspire, and connect. Providing cutting-edge information in an interactive and modern style, the attendees of IMF’s educational seminars and workshops gain a true understanding about the latest significant developments in myeloma. In addition, patients and care partners are able to share their myeloma journeys with each other, as well as to find inspiration in the experiences and resilience of others.
Lastly, IMF educational events are critical reminders that we need each other. We need to connect in a way that is hard to describe. I am constantly humbled and motivated by our myeloma faMMily. Learn more about the PFS and RCW programs at myeloma.org, or just ask Myelo! (If you don’t know who Myelo is, read more in this issue of Myeloma Today about the IMF’s AI Chatbot.)
IMF’s health equity initiatives
The IMF remains committed to health equity as evidenced by our M-Power program, the nationwide initiative to improve the short-term and long-term outcomes of patients with myeloma in Black communities. Myeloma is the most common blood cancer in individuals of African descent. Black patients have twice the risk of developing myeloma when compared to White patients, and their diagnosis is often made later in the disease course. Mortality from myeloma is twice as high in Black patients, who have less access to treatment. The M-Power initiative is breaking down barriers to health equity and raising myeloma awareness, and I am particularly excited about the progress we are making.
As the M-Power program continues to expand, we are having an impact on communities across the country to raise awareness, shorten the time to diagnosis, and enhance access to optimal care. IMF’s M-Power community engagement has formed partnerships with the cities of Atlanta (GA), Baltimore (MD), Charlotte (NC), Detroit (MI), New York City (NY), Tampa (FL), and Richmond (VA).
In June 2024, M-Power returned to New York City to celebrate Juneteenth and host an in-person event in collaboration with Memorial Sloan Kettering Cancer Center and the Abyssinian Baptist Church. Presenters included Yelak Biru (IMF President & CEO) and Dr. Urvi A. Shah (Memorial Sloan Kettering Cancer Center), who discussed the link between food, blood, and cancer. In October 2024, Richmond became the latest partner to join the M-Power initiative and the IMF held our first community meeting there.
One of the many aspects of the M-Power initiative is the IMF’s partnership with the National Medical Association (NMA) and the Cobb Institute, the research arm of the NMA. Together, we aim to foster a community of doctors dedicated to myeloma in African Americans. Although 14% of the U.S. population is African American, only 6% of doctors are African American, and research has shown that patients benefit when their healthcare provider shares their heritage. The Medical Student Scholars for Health Equity in Myeloma program selects the most promising minority candidates, including from Historically Black Colleges and Universities (HBCU), and pairs them with myeloma experts to work on a myeloma-related health disparities project.
At the August 2024 NMA annual conference in New York City, scholars and mentors gathered for a special poster session where the students presented their work. Two of the 2024 projects have already been accepted for presentation in December at the annual meeting of the American Society of Hematology (ASH), one of the premier medical meetings for myeloma specialists, with student scholar Semegne Hiruy, who was mentored by Manisha Bhutani (Levine Cancer Institute, Charlotte, NC), receiving an abstract achievement award! The commitment of the student scholars to health equity is inspirational and gives me so much hope for the future of the medical profession. Programs like this are part of the IMF’s short-term and long-term solutions to health inequity.
Myeloma clinical trials
Several interesting clinical trials that are in progress will inevitably provide new therapies for patients with myeloma, such as next-generation CAR T-cell therapies and bispecific antibodies. As we continue to glean important information from the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) clinical trial in Iceland, we will learn more about the potential of screening for myeloma at an earlier point in its progression. Incidentally, I had the privilege of meeting the iStopMM research team in Reykjavík during the IMF’s Iceland Cycling Expedition (ICE), an incredible life experience of cycling across Iceland with other myeloma doctors, patients, and care partners.
In other exciting news about clinical trials, we may soon see the possible return of Blenrep® (belantamab mafodotin), a monoclonal antibody that was initially approved by the FDA as a single-agent therapy for patients with relapsed or refractory multiple myeloma (RRMM), and was later withdrawn from the market. The withdrawal of Blenrep did not imply that the drug was ineffective. In fact, it demonstrated superiority over the combination of Pomalyst® (pomalidomide) + dexamethasone [Pd], but not to the degree that was sufficient for continued approval.
The development of Blenrep continued, incorporating lessons learned from previous experience. The DREAMM-7 phase III clinical trial compared Blenrep in combination with Darzalex + Velcade + dexamethasone [DVd] vs. DVd without Blenrep, with the Blenrep-based combination demonstrating a greater depth of response, more durable responses, and significantly improved PFS compared to the control group.
The DREAMM-8 phase III clinical trial compared a combination of Blenrep + Pd [BPd] to the combination of Velcade + Pd [PVd] in patients with RRMM after only one prior line of therapy. The Blenrep-based combination outperformed the control group in terms of response rate, durability of response, and PFS.
The implications of the results from these two randomized clinical trials are significant, with Blenrep now poised to re-enter the treatment landscape for patients with RRMM after just one prior line of therapy. Regulatory approvals are still pending.
As I look ahead, I see more progress in myeloma on the horizon, I am optimistic about what the future holds, and I look forward to sharing the latest news with you in the next edition of Myeloma Today.
Visit videos.myeloma.org to watch Dr. Mikhael’s presentation about the top research takeaways from the International Myeloma Society (IMS) meeting in Brazil. Stay informed about the key developments in the field of myeloma! Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, and contact the IMF InfoLine with your myeloma-related questions and concerns. Phone lines are open 9 a.m. to 4 p.m. (Pacific) Monday through Friday at 1.800.452.CURE in the U.S. and Canada and 1.818.487.7455 worldwide. To submit your query electronically, email [email protected].
(This article was first published in the 2024 Fall Edition of the IMF's quarterly publication, Myeloma Today. Read the full publication here.)