outcomes data suggest.
For that reason, and because bone marrow units are profit centers and CAR T-cell therapy reimbursement remains problematic, CAR T in the United States is “effectively being used as a bridge to transplant” – at a cost of more than $1 million per dose, economist Duane Schulthess told attendees at a recent, first-of-its-kind joint European CAR T-cell meeting in Paris, which was cosponsored by the European Hematology Association (EHA) and the European Society for Blood and Marrow Transplantation (EBMT).
“This is the way clinical practice is evolving right now; the price is not allowing enough experimentation for CAR T to flow up and be used in the less-diseased population,” said Mr. Schulthess, managing director of Vital Transformation, a consulting company based in Wezembeek-Oppem, Belgium.
In Europe, there is a slightly different problem in that health technology assessment bodies (HTAs) “have to figure out what they want to do” given the 2018 approvals of the first CAR T therapies there, he said, explaining that the data he presented was from a study commissioned by the Dutch government to help determine “what [CAR T] looks like from an effectiveness standpoint while they’re trying to figure out how much it’s worth and what they should pay.”
“Increasingly these are the big issues,” Mr. Schulthess said.
In August, the European Commission approved tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) on the recommendation of the European Medicines Agency. Kymriah was approved for pediatric and young adult patients up to age 25 years with refractory B-cell acute lymphoblastic leukemia in relapse after transplant or in second or later relapse, as well as for adults patients with relapsed/refractory diffuse large B-cell lymphoma after failing at least two lines of systemic therapy, and Yescarta was approved for the latter and for the treatment of primary refractory mediastinal large B-cell lymphoma after at least two lines of systemic therapy.
The approvals have researchers and clinicians there clamoring for information about the therapy, which is revolutionizing the field of hematologic malignancies, according to Christian Chabannon, MD, PhD, chair of the EBMT Cellular Therapy & Immunobiology Working Party and vice-chair of the EBMT Scientific Council.
“An increasing number of European institutions are starting to administer this new category of medicinal products and increasingly contribute to ongoing clinical protocols and preclinical studies,” Dr. Chabannon said in an interview, explaining the urgency in planning thejust 6 months after the CAR T approvals in Europe.
EHA and EBMT brought together patient advocates, young investigators, and experts from across the globe to present the latest relevant information and data on topics ranging from current trials and experience, CAR T implementation and management, the preclinical and clinical pipelines, various CAR T applications, industry perspectives, and relevant economic issues, he said.
The latter is where Mr. Schulthess came in.
His research involved patient-level treatment pathway data from a database of more than 3 million patients treated with either allogeneic hematopoietic stem cell transplant (allo-HCT) or CAR T therapy across 5 years of experience. The data showed up to 85% response rates for each in the first-line setting. He and his colleagues then looked at therapy choices for those who failed to respond to second-line therapies and at how decisions were made regarding transplant and CAR T therapy – and specifically whether CAR T can be a substitute for transplant.
Ultimately, they looked at 29 allo-HCT recipients and 14 CAR T therapy recipients for a head-to-head comparison of the two treatments and performed an in-depth cost-efficacy analysis using a novel “visual pathology” methodology to account for limitations in the data.
The 3-year relapse-free survival probability was nearly 68% in the transplant recipients and 46% with CAR T.
“Now why is that? [Because] ... these populations are not the same; the CAR T population has a much higher disease burden,” Mr. Schulthess said. “So what we’re seeing [among] actual clinical doctors doing this for real – they are defaulting to bone marrow transplants, except in those cases where they do not have enough time or the patient does not respond. Then and only then are they giving CAR T.”
And that comes back to the fact that bone marrow units make money, he said.
CAR T is costly, and reimbursement can be problematic; these are disincentives for doctors to use CAR T therapy, at least in the United States, and while this is currently “being worked out,” the choice more often is “giving bone marrow transplant first and seeing what happens,” Mr. Schulthess said.
In Europe, that creates “a tough choice” for the HTAs, he said, noting that, in the absence of evidence of CAR T being curative in the subpopulation of patients with high disease burden who fail transplant and given the high cost, there is a push to determine at what point it begins to make sense economically.
“We think that you gain efficiency at ... roughly $277,000 [per dose] because [at that cost] you can do more CAR Ts than you can do bone marrow transplants. [CAR T] is less invasive, it’s lighter touch, it’s more efficient,” he said. “So if we were to see an efficiency cost of between $222,000 and $277,000, we think that works.”
Another recent study came to similar conclusions based on quality assessments, he said (J Clin Oncol. 2018 Sep 13.
“We think that’s where this is going to end up, so we think that, if someone starts producing this for a couple hundred thousand bucks, then – certainly in Europe – it will make sense for this to start drifting up and being used as a substitute [to transplant],” he added.
Mr. Schulthess was one of scores of experts and investigators who presented at the EHA/EBMT joint meeting, which included numerous U.S. pioneers in the field and young European investigators, among others, Dr. Chabannon said.
Attesting to the enthusiasm in Europe regarding CAR T, Dr. Chabannon said that there were “more requests for registration than the venue could safely accommodate, a long waiting list, and a high number of individuals on the waiting list who registered for the live streaming” of the event.
“The field of CAR T cells is growing at a fast pace since the first clinical successes reported in the early 2010s, and one can wonder whether the expectations are not in excess of what reality will deliver,” he said. “Nevertheless, CAR T cells represent an essential innovation, not an incremental progress in biomedical sciences. They combine new mechanisms of action, clinical activity in advanced malignancies (and possibly beyond the field of cancer), transfer of manufacturing of human cell-based therapeutics to the industry, and potentially the first commercial success for a gene therapy.”
Surveys conducted by various professional associations, including EBMT, have clearly identified the potential for clinical successes that CAR T cells represent and the tremendous challenges raised by these innovations, he said, noting that “these include fulfilling specific educational needs.”
Therefore, EBMT and EHA have already announced that a second edition of the meeting is planned for Jan. 30 – Feb. 1, 2020, he noted.
Mr. Schulthess reported that his research was funded by the Dutch government.