Bridging the Divide: Global Equity in CAR T-Cell Therapy Free

Andrew J. Cowan, MD, is an associate professor in the Clinical Research Division of Fred Hutchinson Cancer Center in Seattle.

As I’m sure many of my multiple myeloma (MM) colleagues in the U.S. can agree, the recent approvals of ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) for patients with relapsed MM who have received more than one line and two lines of therapy, respectively, have been exciting but have also led to many conversations about how to prioritize patients. At Fred Hutch, we are fortunate to be able to treat several patients per month with commercial chimeric antigen receptor (CAR) T-cell therapy, yet we still spend countless hours coordinating the care of patients who are awaiting CAR T-cell therapy. Recently, I learned that beyond “bridging therapy” — referring to treatment to control disease after leukapheresis — there is now “holding therapy,” which is meant to control disease while awaiting leukapheresis. Seemingly overnight, new terms and systems have developed to support a whole new population of patients awaiting cellular immunotherapy. However, while we often complain about our inability to treat all the patients we would like, it is astonishing to realize just how privileged we are, here in the U.S., to even have access to these therapies at all!

These disparities were highlighted when I recently traveled to Sydney to attend and speak at the Australia and New Zealand Transplant and Cellular Therapies, or ANZTCT, annual meeting. Although I was there to share our experience at Fred Hutch with CAR T-cell therapy for MM, I attended many of the meeting sessions and came away with new insights about cellular immunotherapies from a global perspective, including how other countries deal with access to cellular immunotherapy for hematologic malignancies.

One of the major themes I took away from the meeting was that although cellular immunotherapies are groundbreaking and transformational for non-Hodgkin lymphoma (NHL) and MM, access to these therapies is quite limited globally, even among high-income regions. We previously showed in a 2018 manuscript on the global burden of MM that even access to our most effective therapies, lenalidomide and bortezomib, is limited globally, with much of sub-Saharan Africa and Central Asia lacking governmental approvals for these drugs.¹ Examining approvals doesn’t even address the major issue — which is whether the drugs will be paid for. We couldn’t obtain data on payor coverage for drugs, which is likely the limiting factor for many globally. Examining global approvals of CAR T-cell therapy for relapsed MM reveals that, even as of today, only a handful of regulatory agencies have approved these therapies, including the U.S. Food and Drug Administration, the European Medicines Agency, the National Medical Products Administration in China, and Japan’s Pharmaceuticals and Medical Devices Agency. This leaves much of the world without access to cellular immunotherapy for relapsed MM.

As I learned from my colleagues, although CAR T-cell therapy for relapsed MM was technically approved by the Australian Therapeutic Goods Authority, negotiation on pricing still needs to be done before patients in Australia can access cilta-cel. In New Zealand, there is unlikely to be access to CAR T-cell therapy for MM in the foreseeable future. Although these are anecdotes, I suspect that in much of the world outside North America, Europe, and Japan, access to these advanced and lifesaving therapies will be out of reach even in the coming years.

Some recently published analyses support what I’ve observed. Many pivotal clinical trials have been conducted outside the U.S., yet approvals in these countries have not always immediately followed. In one fascinating analysis, investigators showed substantial disparities between the countries where new therapies are studied and where they are eventually approved, which fits with my anecdotes mentioned above.²

Even in the U.S., the cost for cellular immunotherapies remains high, at more than $500,000 each for cilta-cel and ide-cel.³ The costs for CD19 CAR T cells for NHL are also at similar levels.³ While Medicare will pay these costs in the U.S., in much of the world, these types of expenditures are not sustainable.

So, how can we ensure better access for cellular immunotherapies on a global level?

• Support engagement and advocacy work with pharmaceutical companies and government agencies. I suspect that greater engagement with pharmaceutical companies, who have invested considerable capital in the development of these therapies and rightfully expect returns, will help. Advocacy for global access by key leaders in the field will likely help raise awareness.
• Increase emphasis on development of local or “homegrown” CAR T-cell therapies. Given the high cost of commercial CAR T-cell therapies, could locally produced “point-of-care” CAR T-cell therapies be feasible, lower-cost alternatives? At the Hospital Clínic de Barcelona in Spain, a “homegrown” B-cell maturation antigen (BCMA) CAR T-cell therapy was developed under a special policy from the Spanish government and then studied, with findings published last year.⁴ The early efficacy and safety data were promising, and after discussions with regulatory authorities, the Spanish Agency of Medicines and Medical Devices approved ARI0002h as a “non-industrially manufactured advanced therapy” for patients with relapsed MM.⁵ The main advantage of a locally produced CAR T-cell product is a dramatic reduction in costs of manufacturing and delivery. If successful, this approach could be applied on a global scale at centers with sufficient technical capabilities as a way to improve access and reduce costs for BCMA CAR T-cell therapy.

To conclude, although the development and approval of CAR T-cell therapy for relapsed MM has provided hope and extended life for many with this disease in the U.S., on a global level, access to these therapies remains limited or nonexistent, even in some high-income countries. I hope some of the ideas mentioned herein can lead to greater access and reduced disparities globally for patients with relapsed MM.

Andrew J. Cowan, MD
Associate Editor

References

1. Cowan AJ, Allen C, Barac A, et al. Global burden of multiple myeloma: a systematic analysis for the global burden of disease study 2016. JAMA Oncol. 2018;4(9):1221-1227.
2. Fatoki RA, Koehn K, Kelkar A, et al. Global myeloma trial participation and drug access in the era of novel therapies. JCO Glob Oncol. 2022;8:e2200119.
3. Cliff ERS, Kelkar AH, Russler-Germain DA, et al. High cost of chimeric antigen receptor T-cells: challenges and solutions. American Society of Clinical Oncology Educational Book. 2023;43:e397912.
4. Oliver-Caldés A, González-Calle V, Cabañas V, et al. Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. Lancet Oncol. 2023;24(8):913-924.
5. Clínic Barcelona. Green light for ARI0002h CAR-T developed by Clínic-IDIBAPS for patients with multiple myeloma. July 19, 2024. Accessed September 9, 2024. https://www.clinicbarcelona.org/en/news/green-light-for-ari0002h-car-t-developed-by-clinic-idibaps-for-patients-with-multiple-myeloma.

The content of the Editor’s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated.

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