He said in his clinical practice, approximately 25% of patients who may be candidates for CAR-T products do not meet the criteria required to complete the procedures. “Many are getting chemo every 2 or 3 weeks, and they have to give the cells necessary for treatment during the window when they are not receiving chemo,” said Dr Andreadis. “How to [collect] the cells at the right time for the patients is an issue.” He also noted that blood counts have to be fully recovered prior to administration of the chemotherapy used as preparation for the final CAR-T product.
Bijal D Shah, MD, of the Moffitt Cancer Center in Tampa, Florida, told Hematology Advisor that the optimal management strategy for patients waiting for approval depends on the health of the patient and other factors. “This is controversial, and I am not sure anyone has a good answer,” Dr Shah said. “The goal is to provide disease control without adversely impacting the T-cell collection needed for CAR-T manufacturing. In DLBCL, high-dose steroids and targeted radiation to symptomatic lesions are often employed. Debulking chemotherapy using lower intensity regimens such as gemcitabine and oxaliplatin and targeted therapy [using agents] such as ibrutinib can also be beneficial for selected patients.”
Dr Shah added that there are fewer options for patients with B-cell ALL, as many will have already been treated with conventional salvage options, including blinatumomab and inotuzumab, prior to CAR-T therapy. “Similar to [how we manage patients with] DLBCL, we more often utilize steroids, and occasionally hydroxyurea, in this setting.”
Matthew Carabasi, MD, senior director of strategic oncology partnerships at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania, noted that CAR-T therapy does not work in a number of patients, but he believes it is highly valuable, and treatment delays should be addressed immediately.
“I do not believe the potential impact of CAR-T therapy has been oversold to the public,” he told Hematology Advisor. “I say this because it is one of those very rare therapies that has demonstrated the ability to cure patients with even the most advanced disease and whose immune systems may already be significantly weakened by both their diagnosis as well as prior treatments.”
Dr Carabasi further explained that the results that are now being achieved with CAR-T therapies may improve as CAR-T therapy is used in less heavily pretreated patients whose disease may be more susceptible to immune mechanisms, and at a time when their immune systems are more capable of generating and supporting CAR-T activity. Dr Carabasi added ongoing and future clinical trials should help clarify the utility of CAR-T therapy for the currently approved indications as well as for new targets such as multiple myeloma and chronic lymphocytic leukemia, diseases that are rarely cured with currently available approved treatments.
The use of CAR-T products is only in its infancy and is very much evolving. Some clinicians believe that once certain hurdles are overcome, there will be significant advantages with this approach. “[Although] the current prices are high, a single application of curative therapy may be cost-effective when compared to indefinite treatment with other agents that, over time, are as costly and offer no chance for cure,” said Pierluigi Porcu, MD, director of the division of hematologic malignancies and hematopoietic stem cell transplantation at the Sidney Kimmel Cancer Center at Thomas Jefferson University.
If CAR-T therapy eventually diminishes or even eliminates the need for long courses of radiation and chemotherapy, he said, it may reduce the risk and associated cost of long-term complications, such as secondary cancers. “Given the size of the potential market, as well as the significant ongoing research by multiple companies, it is not unreasonable to assume that over time, newer CAR-T products will be less expensive, cause fewer side effects, and be even more effective,” Dr Porcu stated.
Disclosures: This study was funded by Novartis. In addition, some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Snider JT, Brauer M, Kee R, et al. The potential impact of CAR T-cell treatment delays on society. Am J Manag Care. 2019;25(8):379-386.