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Evaluating Real-World Outcomes, Access Barriers and Scientific Progress: Introduction to U.S. Myeloma Innovations Research Collaborative (USMIRC) Group

Advancements in medical research are constantly transforming oncology care, bringing new hopes to patients, and posing fresh challenges for clinicians. U.S. Myeloma Innovations Research Collaborative (USMIRC) group is a collaboration among U.S. Seven academic institutions that came together to publish real-world data on various aspects of Multiple myeloma (MM) care, chimeric antigen receptor T-cell (CAR-T) therapy and other innovative treatments. We started the USMRIC to report the real-world outcomes of the patients and to bridge the gap between the understanding of real-world patients and the clinical trials, especially focusing on safety and toxicities in novel MM therapies and to demonstrate the feasibility of the broader applicability of MM therapy. Our platform can analyze and challenge the “Risk Evaluation and Mitigation Strategy” (REMS) drug safety program by optimizing monitoring periods for better cost efficiency, access, and without compromising safety, identifying early prognostic markers in multiple myeloma. Additionally, our efforts to address treatment access disparities and our dedication to nurturing future medical professionals highlight the comprehensive approach needed for progress in modern oncology. Here, we share key findings from our research, stressing the importance of scientific advancement and equitable access to care.

At the 2024 American Society of Transplantation and Cellular Therapy (ASTCT) meeting, we presented multiple abstracts of real-world outcomes using our database. In a study investigating the incidence of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) among patients treated with CAR-T therapy, USMIRC found that the mandatory 4-week monitoring period can be adjusted depending on the stability of the patient and CAR-T product, allowing for cost reduction and increased access to treatment (1). In a cohort of patients who received commercial BCMA-targeting autologous CAR-T cells, bone marrow (BM) BCMA detection emerged as a potential prognostic marker in multiple myeloma (MM) patients. A prospective study showed that nearly all (91%) patients exhibited BM-BCMA resurgence detected by flow cytometry before or at the same time as clinical relapse. These findings suggest that BM-BCMA could serve as an early indicator of relapse, potentially allowing for preemptive intervention (2).

While biosimilar Filgrastim-aafi (Nivestym) continues to be used widely, data is lacking regarding its efficacy compared to Filgrastim (Neupogen) for use among healthy donors for allogenic HSCT mobilization. USMIRC efforts showed comparable efficacy between the two, indicating that biosimilar Filgrastim-aafi (Nivestym) is a viable alternative for peripheral blood stem cell  mobilization for autologous stem cell transplant (3).

Our real-world study of Idecabtagene Vicleucel (ide-cel) in relapsed-refractory MM demonstrated its efficacy and safety in patients who did not meet the strict Karmma-1 trial criteria, suggesting a broader applicability of this therapy (4). Similarly, the study on frailty and CAR-T cell therapy highlighted that frailty, not age, was a better indicator for patient outcomes following CAR-T. It also demonstrated similar safety outcomes, albeit with inferior efficacy among frail patients (5). CAR-T trials have largely excluded patients with heart failure, creating challenging situations for clinicians treating such cases. Our study into permissive cardiotoxicity showed CAR-T can be safely administered to medically optimized heart-failure patients with good performance (6).

Access to CAR-T therapy and other innovative treatments is a significant challenge, especially for patients in rural and underserved communities. Our retrospective database review highlighted the disparities in access to CAR-T therapy, indicating that patients from rural and Health Professional Shortage Areas (HPSAs) are significantly less likely to receive these advanced and often costly treatments. The research reveals that the majority of CAR-T therapy recipients are urban, white, and live near treatment centers, with almost no black patients from rural areas receiving the therapy. This geographic and demographic disparity highlights the need for further initiatives aimed at improving access to CAR-T therapy, especially in underserved regions (7).

TACTUM and GLAMM surveys are instrumental in addressing these access issues. Specifically, TACTUM 23 focuses on understanding, treating, and referring physicians' perspectives regarding access to BCMA-directed cellular therapies (BDCT). The authors of the study found that financial burden, limited treatment capacity, and relocation requirements are significant barriers to access. To overcome these challenges, the study suggests developing outpatient BDCT programs and clearer guidelines for patient transfers post-treatment (8). Similarly, the GLAMM1 study identifies global barriers to accessing CAR-T and T-cell-engaging bispecific antibodies (TCE). It highlights the financial burden as a primary obstacle, even in high-income countries, with many regulatory barriers also playing a significant role in Europe. The study calls for enhanced collaboration between oncologists, pharmaceutical companies, and policymakers to mitigate these barriers to ensure broader access to these life-saving therapies globally (9).

USMIRC is unique because its focus on nurturing the next generation of medical professionals. The consortium prioritizes the development of careers by actively training and showcasing young faculty, mentees, and trainees to ensure that the skills required for cutting-edge research and treatment are passed on to future leaders in oncology. USMIRC's unique model involves mentoring medical students, residents, hospitalists aspiring to be oncologists, and fellows, providing them with hands-on experience and opportunities to present their research. At the 2024 ASTCT meeting nine early career physicians or residents presented abstracts. Led by the experienced, dedicated, and growing team of mentors from collaborating institutions, this initiative has resulted in a significant number of additional young professionals being trained and subsequently planning on presenting their findings at major conferences.

Overall, USMIRC’s dual focus on improving access to care and developing careers not only advances scientific knowledge and research but also ensures that the benefits of these advancements reach a broader patient population while building a robust pipeline of future leaders in the field.

References:

1.            Wesson W, Dima D, Davis J, Rashid A, Furqan F, Saif MSI, et al. A Multicenter Experience: Duration of Mandatory CRS and Icans Monitoring for Myeloma and Lymphoma CAR-T Recipients. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy. 2024;30(2):S207-S8.

2.            Rashid A, Wesson W, Tabak C, Lutfi F, Mushtaq MU, McGuirk JP, et al. BCMA Re-Emergence: Can It Serve As a Prognostic Biomarker in Multiple Myeloma after CAR-T? Transplantation and Cellular Therapy. 2024;30(2, Supplement):S194-S5.

3.            Shahzad M, Amin MK, Al-Ramahi JS, Khalid MF, DeJarnette MS, Mahmoudjafari Z, et al. Comparison of Biosimilar Filgrastim (Nivestym) Versus Originator Filgrastim (Neupogen) for Peripheral Blood Stem Cell Mobilization for Allogeneic Hematopoietic Stem Cell Transplantation. Transplantation and Cellular Therapy. 2024;30(2, Supplement):S172.

4.            Dima D, Rashid A, Davis JA, Awada H, Abdallah A-O, Li H, et al. Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in Patients with Relapsed-Refractory Multiple Myeloma (RRMM) Not Meeting the Karmma Trial Eligibility Criteria: A Real-World Multicenter Study. Blood. 2023;142(Supplement 1):4885-.

5.            Davis JA, Dima D, Ahmed N, DeJarnette S, McGuirk J, Jia X, et al. Impact of Frailty on Outcomes after Chimeric Antigen Receptor T Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma. Transplant Cell Ther. 2024;30(3):298-305.

6.            Lutfi F, Ansari B, Hawa A, Abdallah A-O, Shah Z, Hoffmann M, et al. Permissive Cardiotoxicity As a Guiding Principle to CAR-T Therapy with Reduced Ejection Fraction Heart Failure. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy. 2024;30(2):S229.

7.            Tabak C, Rashid A, Pepper S, Wesson W, Abdallah A-O, Lutfi F, et al. Chimeric Antigen Receptor T-Cell (CAR-T) Access Among Rural and Health Professional Shortage Area (HPSA) Populations in the Midwest. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy. 2024;30(2):S323.

8.            Atallah R, Saif MSI, Danai D, Shrestha A, Anwer F, Mushtaq MU, et al. The TACTUM23 Study: Access to Cellular Therapies in Multiple Myeloma: Perspectives of Treating Versus Referring Physicians in 2023. Transplantation and Cellular Therapy. 2024;30(2, Supplement):S375-S6.

9.            Atallah R, Shatnawi Y, Mammadzadeh A, Hashmi SK, Rana SK, Mushtaq MU, et al. The GLAMM1 Study - Global Access to Myeloma Medications: Potential Barriers to Chimeric Antigen Receptors (CART) and T-Cell-Engaging Bispecific Antibodies (TCE) Globally. Blood. 2023;142(Supplement 1):3327-.