Dennis Cooper, MD, chief of blood and bone marrow transplantation at Rutgers Cancer Institute of New Jersey and attending physician at Robert Wood Johnson University Hospital, New Brunswick, New Jersey, who was not involved in the research, questioned the trial’s definition of high-risk patients. 

He pointed out that some studies have questioned the efficacy of the Deauville score as a good predictor of bad prognoses. The largest is the “PET-guided therapy of aggressive non-Hodgkin’s lymphomas” (PETAL) study, which found that a positive interim PET scan, as defined by a decrease of the maximum standardized uptake value (SUVmax) by 66% or less, was effective in predicting patients who will have poor prognoses, although intensifying chemotherapy based on this measure was determined not effective.2 When researchers conducted a post-hoc analysis of the PET scans using the Deauville score, they found this was not effective for the prediction of event-free and overall survival. “I think it’s not been validated as a way of identifying patients who are unlikely to do well,” Dr Cooper said. 

Regardless, he expects the results to be “more hypothesis-generating” rather than definitive. “If a patient they identify as high-risk does well, do we really know whether it was the CAR T-cell [therapy], or were they destined to do well anyway?” he questioned. Only a randomized trial can answer that question, he said. 

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An additional concern is that unless the prices of CAR-T therapies decrease significantly, their use as first-line therapies are going to price themselves out of being feasible, Cooper added. Axi-cel, for instance, carries a price tag of $373,000. A recent study in the Journal of Clinical Oncology examining the cost effectiveness of axi-cel and tisagenlecleucel found that if every patient currently eligible for a CAR-T treatment as a third-line therapy were to receive it, this could raise the US health care budget by $10 billion dollars over 5 years.3 

“Now if you decide that you’re going to give this to patients with upfront disease . . . it’s going to be even more expensive,” Dr Cooper explained. Prices may come down with increasing competition in the future, he added, “but they certainly need to come down quite a bit to make them more palatable.” 

Disclosure: The investigators disclosed various ties to pharmaceutical companies in this abstract. For a full list of disclosures, please refer to the original abstract. 

References

  1. Neelapu SS, Chavez JC, Lin Y, et al. ZUMA-12: A phase 2 multicenter study of axicabtagene ciloleucel as a first-line therapy in patients with high-risk large B-cell lymphoma. Poster presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract TPS7574.
  2. Dührsen U, Müller S, Hertenstein B, et al. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial [published online May 11, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.8093
  3. Lin JK, Muffly LS, Spinner MA et al. Cost effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma [published online June 3, 2019]. J Clin Oncol. doi: 10.1200/JCO.18.02079