Kathy Giusti, MBA
When I was diagnosed with multiple myeloma in 1996, I was given 3 years to live. At the time, there was little understanding of this disease, which was termed incurable. There were no new treatments, few drugs in the pipeline, hardly any clinical trials, and no multiple myeloma community or ecosystem.
Today, the situation is very different. Tremendous progress has been made over the past 2 decades, and I have enormous hope for the future based on the promise of exciting new science. Our collective challenge is accelerating the pace of getting these amazing new scientific discoveries to all patients.
I have had a unique vantage point on the revolution in care for multiple myeloma based on my personal experiences as a patient, founder of the Multiple Myeloma Research Foundation (MMRF), and cofounder of the Harvard Business School Kraft Precision Medicine Accelerator. Based on this vantage point, I want to celebrate how far we’ve come in treating multiple myeloma, share why I am so hopeful about the future, and offer recommendations to accelerate the final mile in delivering therapies and cures to all patients.
Celebrating the Progress of the Myeloma Community
There is so much good news to celebrate in the treatment and outcome of myeloma. Let me offer these five reasons for my increasing optimism for both newly diagnosed patients with the cancer and for those experiencing recurrent disease. Let me also offer my immense gratitude to the entire myeloma community for this success.
Number of Treatments: In 1996, no new treatments had been approved in years. Today, there are 14 treatments that have been approved by the U.S. Food and Drug Administration (FDA) for multiple myeloma.1
Survival Rate: When I was diagnosed, the survival rate was approximately 3 years. Today, it is closer to 10 years and is continuing to increase.
Potential Standard of Care: The four-drug regimen of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone has shown promising results and could become a standard of care in the initial treatment of multiple myeloma.
Emergence of MRD as a Metric: Measurable residual disease (MRD) can now be assessed more deeply and easily. There is now a greater ability to use MRD to help guide treatment decisions.
Robust Pipeline: There is a robust pipeline of therapies and clinical trials for patients with relapsed and refractory myeloma.
This progress has been possible because so many parties have worked together. Funders have provided significant financial resources. Scientists, researchers, and pharmaceutical companies have made breakthrough discoveries and brought them to market. Clinicians have orchestrated clinical trials and cared for patients. And patients have participated in clinical trials, provided tissue samples, had their genome sequenced, and bravely continued to receive care.
In this myeloma ecosystem, the MMRF has played an important role in providing funding for research, generating and sharing data, developing collaborative models, and accelerating drug development. The MMRF’s contributions include the following:
Recognizing the Hope and Promise of the Future
Where we are today—and where we are going—gives me so much hope. My hope is based on the first chimeric antigen receptor (CAR) T-cell drugs gaining FDA approval, the promise of bispecific antibodies, the robust immunotherapy pipeline, and the emergence of innovative diagnostics.
The Promise of CAR T-Cell Therapy: The first CAR T-cell therapy for relapsed or refractory multiple myeloma, idecabtagene vicleucel, received FDA approval in March 2021. The second CAR T-cell therapy for multiple myeloma, ciltacabtagene autoleucel, was approved by the FDA earlier this year. Ciltacabtagene autoleucel is particularly exciting because the results from clinical trials show a high rate of patient response, with 98% of patients responding to therapy and 78% of these patients experiencing a stringent complete response, and MRD negativity of 10-5 was achieved in 92% of evaluable patients.2 In many previous trials of multiple myeloma drugs, MRD negativity was not even measured.
“There is now hope that what was once considered an incurable disease [multiple myeloma] may soon be curable. What was once inconceivable is now conceivable.”— Kathy Giusti, MBA
Tweet this quote
The Promise of Bispecific Antibodies: Bispecific antibodies and bispecific T-cell engagers are off-the-shelf drugs similar to many therapies already prescribed to patients, including monoclonal antibodies. However, bispecific antibodies are not just antibodies against one cell; they bring the patient’s T cells close to the tumor cell without any need for genetic engineering. Compared with CAR T-cell therapies, bispecific T-cell engagers are a simpler way to get T cells to attack cancer cells, but they require multiple doses.3
Part of the promise of bispecific antibodies is that unlike CAR T-cell therapy, which is administered only in academic medical centers, there might be potential for third and later doses of these agents to be given in a community-based hospital’s outpatient infusion center.
In a recent article, Nina Shah, MD, Professor of Clinical Medicine at the University of California, San Francisco, and Chair of the Society for Immunotherapy of Cancer (SITC) Multiple Myeloma Immunity Guideline panel, said that if a bispecific T-cell engager is approved by the FDA, it “would be a game-changer for clinical management of these diseases.” 3 However, bispecific T-cell engagers are earlier in their development than CAR T-cell therapies, and there is still a great deal to be learned about their effectiveness and durability in myeloma in clinical trials.
The Promise of Other Immunotherapies: Among the reasons for my optimism is the tremendous immunotherapy pipeline for multiple myeloma, which will provide more shots on goal. More shots on goal will produce more goals. The current pipeline includes more than 20 CAR T-cell therapies in phase I or II trials and 15 bispecific antibodies (including both bispecific antibodies and bispecific T-cell engagers).4 Other immunotherapies in the pipeline are naked antibodies, antibody-drug conjugates, checkpoint inhibitors, and natural killer cell and T-cell therapies as well as many novel agents. In total, there are more than 200 active therapeutic trials currently taking place, including for immunotherapies (see ClinicalTrials.gov for further details).
Working Together to Accelerate the Last Mile
The myeloma ecosystem has produced amazing scientific discoveries, with many more in various stages of development. Although the scientific pipeline is working to produce more breakthroughs, let’s work together to get the treatments we have to patients even faster. Here are three recommendations.
Creating and Disseminating Standards of Care: There are now several options available to clinicians for treating patients at different stages of myeloma. Let’s use our collective knowledge to establish standards of care to guide treatment and communicate these standards broadly to community oncologists, so they know the best options for treating their patients with multiple myeloma. For example, in clinical trials, the four-drug regimen mentioned previously (daratumumab, bortezomib, lenalidomide, and dexamethasone) showed improved stringent complete response rates and MRD negativity vs a three-drug combination that excludes daratumumab; both stringent complete response and MRD negativity deepened over time.5
Sharing Knowledge About Recently Approved Treatments and Soon-to-Be Available Innovations: Let’s make sure clinicians and patients are aware of the recently approved CAR T-cell therapy, ciltacabtagene autoleucel, and where it is available, so physicians can direct appropriate patients for this treatment. Also, let’s ensure that clinicians are aware of clinical trials for bispecific antibodies and other promising treatments, so they can refer their patients to participate in these trials. In addition, as the first bispecific antibody for myeloma, teclistamab, nears FDA approval and becomes commercially available, which is expected in late 2022, it is important to create greater awareness of this breakthrough among community oncologists. This treatment will provide a broader available alternative to CAR T-cell therapies and other treatments that are currently available only in academic medical centers. Together, we must create awareness of what is currently available and prepare for what is coming soon.
Enrolling More Diverse Patients Into Clinical Trials: Curing diseases for all patients requires that all patients are proportionately represented in clinical trials. However, historically, clinical trials for multiple myeloma have not included enough minority patients, especially Black patients, who have higher mortality rates than White patients and have not experienced the same survival gains over time.6 As I recently wrote in the Harvard Business Review, we must ensure representative participation in clinical trials.7 Strategies for eliminating disparities and achieving better representation of minorities in trials include the formation of networks and partnerships involving both academic medical centers and community-based hospitals and health systems, especially in areas with large numbers of minority patients. In addition, we must increase the diversity of principal investigators, add positions such as community-based patient navigators to recruit minority patients, and engage in community outreach to educate and attract more minority patients to participate in clinical trials.
I am so grateful for the amazing progress we’ve made together, which has kept me and so many other patients alive. I am also incredibly optimistic about the future. There is now hope that what was once considered an incurable disease may soon be curable. What was once inconceivable is now conceivable.
But we can’t delay. My continued sense of urgency is due to knowing so many patients who are no longer with us because the scientific breakthroughs in the development pipeline did not get to them fast enough. Today, we have the potential to cure some patients. We want to move quickly to be able to cure all patients. This means working together to accelerate turning great science into approved treatments and then going the last mile to get these treatments to each and every patient. We also must work together to convey the many lessons we have learned in multiple myeloma to accelerate the development of treatments for other cancers and diseases.
I have never been more grateful, and more hopeful, and I have never felt more urgency to persevere.
DISCLOSURE: Ms. Giusti is on the board of the biotechnology company EQRx.
1. Multiple Myeloma Research Foundation: Finding a Cure. Available at https://themmrf.org/finding-a-cure/. Accessed April 7, 2022.
2. Martin T, Usmani SZ, Berdeja JG, et al: Updated results from CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. 2021 ASH Annual Meeting & Exposition. Abstract 549. Presented December 12, 2021.
3. Amorosi D: The ‘eharmony of immunotherapy’: Bispecific T-cell engagers vs. CAR-T for multiple myeloma. Helio News, December 3, 2021. Available at www.healio.com/news/hematology-oncology/20211202/the-eharmony-of-immunotherapy-bispecific-tcell-engagers-vs-cart-for-multiple-myeloma. Accessed April 7, 2022.
4. Multiple Myeloma Research Foundation: Clinical trials and experimental therapies. Available at https://themmrf.org/multiple-myeloma/treatment-options/clinical-trials-and-experimental-therapies/. Accessed April 7, 2022.
5. Voorhees PM, Kaufman JL, Laubach J, et al: Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: The GRIFFIN trial. Blood 136:936-945, 2020.
6. Marinac CR, Ghobrial IM, Birmann BM, et al: Dissecting racial disparities in multiple myeloma. Blood Cancer J 10:19, 2020.
7. Giusti K, Hamermesh RG, Krasnow M: Addressing demographic disparities in clinical trials. Harvard Business Review, June 11, 2021. Available at https://hbr.org/2021/06/addressing-demographic-disparities-in-clinical-trials. Accessed April 7, 2022.
Ms. Giusti is the Founder of the Multiple Myeloma Research Foundation and Cofounder of the Harvard Business School Kraft Precision Medicine Accelerator.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.