CAR-T Cell Therapy Continues to Change the Cancer Treatment Landscape

Since the first FDA approval of tisagenlecueucel (Kymriah) in August 2017 to treat children and young adults with B-cell acute lymphoblastic leukemia (ALL)¹, CAR-T cell therapy continues to expand in use and improve outcomes for patients with various types of hematologic malignancies.

Months after tisagenlecueucel’s approval, axicabtagene cioleucel (Yescarta) was approved to treat adults with aggressive, relapsed or refractory diffuse large B-cell lymphoma (DLBCL)², and then in May 2018, tisagenlecuecel earned another FDA approval for the same indication. And experts say more trials and approvals may be coming. “This is a promising new therapy. Many trials are in progress and I think lots of new [CAR-T] products and trials are coming, too,” said Misty Lamprecht, MS, APRN-CAN, AOCN, BMTCN, a clinical nurse specialist at The Ohio State University James Cancer Hospital.

Lamprecht joined JC Villasboas Bisneto, MD, a hematology oncologist at the Mayo Clinic, at the ONS 44th Annual Congress³ to discuss the promise — and potential adverse events (AEs) – of CAR-T cell therapy.

“We’ve seen responses out of proportion compared to what we’ve had before, and we see that these responses are lasting,” Bisneto said, noting that in the phase II ZUMA-1 trial that led to the initial approval of axicabtagene ciloeucel, there was an overall response rate (ORR) of 82% and a complete response (CR) rate of 54%.⁴ In the JULIET trial, which analyzed tisagenlecleucel in relapsed or refractory DLBCL, there was an ORR of 54% and a CR rate of 40%.⁴ This is a clear improvement from the SCHOLAR-1 trial, which tested standard chemotherapy in this patient population and showed a 26% ORR and 8% CR rate.⁵

While CAR-T cell therapy has yielded exciting results for patients with blood cancer, this class of agents also comes with significant toxicities.

Cytokine release syndrome (CRS) is one of the major AEs that oncology nurses should look out for, explained Lamprecht. The syndrome, which is associated with T cell expansion, usually happens between 1 and 14 days after cell infusion, and can present with the following symptoms: fever, nausea, vomiting, diarrhea, hypotension/tachycardia, hypoxia/tachypnea, and rash. CRS can range from grade 1 to 4, where grade 4 is typically treated with steroids (dexamethasone or methylprednisone).³ All cases should be assessed for infection, too.

One-third to half of patients receiving CAR-T cell therapies experience infections, with 16% to 33% of them being grade 3 or higher³, so nurses and other healthcare practitioners should evaluate and treat their patients for sepsis in addition to cytokine release syndrome if applicable. “Don’t be blinded by the fact that the patient has gotten CAR-T cell therapy,” Lamprecht said. “They are very immunocompromised, so don’t forget the risk of sepsis. It’s very real.”

Another common AE that patients on CAR-T cell therapy may experience is neurotoxicity, which can happen in 2 phases: first on days 0 through 5 and then after day 5. The patient should receive a full neurologic examination to rule out other causes of their symptoms. Then, practitioners use the Immune Effector Cell-associated Encephalopathy (ICE) assessment to evaluate and grade their patients’ neurotoxicity. The assessment includes orientation questions, sentence writing, following commands, object naming, and counting/spelling backwards.

Lamprecht mentioned that patients experiencing grade 1 neurotoxicity may be concerned because they are having a difficult time finding their words. Grade 2 and beyond, where the patient may not be as cognizant of what is going on, becomes frightening for the caregivers, she added.

“It can be really scary if you’re not prepared for it,” Lamprecht said. “That family support piece is really necessary.”

Research is currently being done to not only create better CAR-T cell therapies, perhaps with fewer AEs, but also to bring the treatment to different realms of the cancer world.

“I believe the holy grail for CAR-Ts in the next year is bringing CAR-T cell therapy to solid tumors,” Bisneto said. “We’re just seeing a new way of treating diseases at large.”

References

• FDA approval brings first gene therapy to the United States. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm574058.htm. Accessed April 16, 2019.
• FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm. Accessed April 16, 2019.
• Lamprecht M, Villasboas JC. CAR T: Where We Are and Where We Are Going. Presented at: ONS 44th Annual Congress; April 11-14, 2019; Anaheim, CA. Abstract 2115. https://ons.confex.com/ons/2019/meetingapp.cgi/Session/2115
• Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (Axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Presented at: 2017 AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract CT019.
• Schuster SJ, Svoboda J, Chong EA, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. NEJM. 2017;377:2545-2554. doi: 10.1056/NEJMoa1708566.
• Crump M, NeelapuSS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. doi:10.1182/blood-2017-03-769620.