NEW YORK — Chimeric antigen receptor T cell therapies could be the breakthrough hematologists have sought to effectively treat certain patients with lymphoma, according to a presenter at HemOnc Today New York.
The FDA has approved two CAR T-cell therapies. Axicabtagene ciloleucel (Yescarta, Kite) — a CD19-directed genetically modified autologous T-cell immunotherapy — is approved for certain adults with large B-cell lymphoma. Tisagenlecleucel (Kymriah, Novartis) — a CD19-directed genetically modified autologous T-cell immunotherapy — is indicated for the treatment of certain adults with large B-cell lymphoma, as well as certain children and young adults with B-cell acute lymphoblastic leukemia.
Aggressive research is underway into armored CARs, dual-targeting CARs and CRISPR CARs, according to Nirav Shah, MD, assistant professor at Medical College of Wisconsin.
“[CAR T-cell therapy] has very much changed the landscape on how we think about [lymphoma] and what the future treatment is going to be for diseases like this,” Shah said during his presentation. “It’s likely that, with all of the research we have going on, the CAR T cells we have now may be obsolete when new-generation CAR Ts come in the next 5 to 10 years.”
Shah outlined three of the key clinical trials that have examined the efficacy and safety of CAR T-cell therapy.
The phase 2 JULIET trial included 93 heavily pretreated adults with relapsed or refractory diffuse large B-cell lymphoma.
Nineteen-month follow-up data presented in December at ASH Annual Meeting and Exposition showed tisagenlecleucel induced durable responses.
Researchers reported a 52% (95% CI, 43-64) overall response rate, with 40% of patients achieving complete response and 12% achieving partial response. Response rates appeared consistent among patient subgroups, including those with double-hit or triple-hit lymphoma and those who had prior autologous stem cell transplant.
Investigators saw no relapses beyond 11 months after infusion.
The ZUMA-1 trial enrolled 111 patients with DLBCL, primary mediastinal large B-cell lymphoma and transformed follicular non-Hodgkin lymphoma who received axicabtagene ciloleucel.
Initial results showed an overall response rate of 82%, with 52% of patients achieving complete response.
Updated results based off 27-month follow-up showed that 39% of patients remained in remission. Median OS had not been reached.
A third trial evaluated lisocabtagene maraleucel (JCAR017; Celgene, Juno Therapeutics) — an investigational CD19-directed CAR T-cell product — for 69 patients with DLBCL. Results showed a 37% complete response rate at 6-month follow-up.
The cost of therapy, as well as the potential of severe toxicity — including cytokine release syndrome — must continue to be addressed as CAR T-cell therapy evolves, Shah said.
“This therapy is effective, it can be durable and it likely can be a cure for some patients,” Shah said. “Clearly there are a significant number of patients who still do not benefit from CAR T-cell therapy and we need advancements in this field to treat their disease.”– by John DeRosier
Reference s :
Shah N. CARs: Out of the showroom and into the clinic. Presented at: HemOnc Today New York; March 21-23, 2019; New York.
Neelapu S et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1707447.
Schuster S et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1804980.
Shah reports consultant fees from Juno Therapeutics, contracted research from Miltenyi Biotec, and stock ownership in Exelixis, Geron and OncoSec.