Other selected trials on CAR-T in blood cancers include a phase 3, randomized study (ZUMA-7) comparing the efficacy of axi-cel with standard-of-care therapy in patients with relapsed or refractory diffuse LBCL (ClinicalTrials.gov Identifier: NCT03391466)and a phase 2 study examining the efficacy and safety of another anti-CD19 CAR-T product, lisocabtagene maraleucel (liso-cel), in patients with aggressive B-cell non-Hodgkin lymphoma who have relapsed or are refractory to frontline treatment with chemoimmunotherapy (ClinicalTrials.gov Identifier: NCT03483103).
Following leukapheresis, ZUMA-12 participants must wait almost 3 weeks for CAR-T cells to be manufactured, Dr Ujjani said. Those patients with rapidly progressing disease may receive non-chemotherapy-based bridging therapy to control the disease in the interim. Participants will then receive conditioning chemotherapy before receiving an infusion of CAR-T. Investigators will undertake first tumor assessments after 28 days, Dr Ujjani said.
The primary outcome measure is the complete response (CR) rate up to 2 years per the Lugano classification. Secondary outcome measures include the objective response rate up to 2 years, event-free survival, and overall survival up to 5 years, as well as CAR-T and cytokine levels that are still in the blood up to a year. “I would like to see a signal suggesting that we can improve outcomes for these patients compared to the outcomes that currently exist with stem cell transplant later on, or even giving CAR-T after the second line [of treatment],” Dr Ujjani said.
Stephen Ansell, MD, PhD, a professor of medicine at the Mayo Clinic in Rochester, Minnesota, who isn’t involved in the study, said he finds the trial an appropriate one for this patient group given their poor prognosis with routine therapies. “Their long-term outcome is actually very poor compared to the rest of the patients, so it’s quite acceptable and quite appropriate to test a different approach in this population,” he said.
One of the challenges clinicians typically face in treating high-risk LBCL is that because patients may not be sensitive to chemotherapy, it often hasn’t been possible to get the disease under sufficiently good control to be able to employ approaches such as allogeneic stem cell transplantation. “This is now taking an entirely different approach,” Dr Ansell said. “The reason that there’s optimism for this is that these patients generally have a low burden of disease and their immune system is still in good shape, because it hasn’t been hammered by a lot of chemotherapy.”
The trial’s results will also shed light on the efficacy of CAR-T in patients with few previous lines of therapy, as well as the risks of side effects such as cytokine release syndrome and neurological toxicities, Dr Ansell said. “The patients in this trial will only ever receive 2 cycles of relatively modest chemotherapy, and then those T cells will be turned into a CAR T-cell product.” He sees 2 potential outcomes from treating these patients with CAR-T earlier: “One is, that it’s a much more useful, young, enthusiastic T cell, and therefore, turns into a much better CAR T-cell . . . But equally, a young enthusiastic T cell may be much more exuberant in [its] response, and therefore, side effects might be increased,” he explained.