This article is more than 5 years old. Information may no longer be current.
High-intensity bridging therapy before CAR T-cell infusion does not improve outcomes in leukemia subset
Click Here to Manage Email Alerts
CHICAGO — Patients who received high-intensity bridging chemotherapy before CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory acute lymphoblastic leukemia demonstrated significantly higher risk for infection than patients who received low-intensity or no bridging therapy, according to data presented at ASCO Annual Meeting.
Additionally, bridging chemotherapy, regardless of intensity, was not associated with improved outcomes after CD19 CAR T-cell therapy.
“We wanted to understand the role of bridging chemotherapy in the clinical management of CAR T-cell therapy in patients with ALL,” Karlo Perica, MD, PhD, medical oncology fellow at Memorial Sloan Kettering Cancer Center and one of the study’s co-authors, told HemOnc Today. Perica explained that the bridging period takes place after the patient’s cells are harvested and sent out for manufacturing, before reinfusion back into the patient. The process can take from 2 to 6 weeks.
“These are often quite sick patients with rapidly growing leukemias, and so they are vulnerable to tumor progression or complications during this period,” he said. “Furthermore, there is some evidence that patients with less tumor [burden] before CAR T-cell infusion have fewer toxicities and more durable responses, so theoretically it might be beneficial to reduce their tumor burden with aggressive chemotherapy before infusion.”
Perica and colleagues performed a retrospective analysis of adults who received CAR T-cell therapy for relapsed or refractory ALL from a previously published study of patients treated at Memorial Sloan Kettering to determine what, if any, bridging therapy was given before CAR T-cell infusion.
“This study spanned a more than 5-year period from really the beginnings of CAR therapy to a period where we had significantly more experience, and so even though the patients were not randomized to different bridging treatments, our investigators chose a number of different strategies,” Perica explained.
The researchers divided the study population for the bridging chemotherapy analysis into two groups. The low-intensity group included patients who received maintenance and/or less myelosuppressive therapies or did not require bridging therapy. The high-intensity group include patients who had remission-inducing or myelosuppressive therapies.
The analysis included 53 patients who received CAR T-cell therapy for ALL; 19 patients had high-intensity and 34 had low-intensity bridging chemotherapy before CAR T-cell infusion. The number of previous therapies, disease burden before bridging therapy, and previous transplant status were similar between the two groups.
The results showed that high-intensity chemotherapy was associated with a higher rate of grade 3 or grade 4 infectious complications during the bridging period than low-intensity chemotherapy (78% vs. 32%; P < .002).
Researchers observed no association between bridging chemotherapy intensity and RFS, post-CAR T-cell infusion grade 3 or grade 4 cytokine release syndrome (CRS) or post-CAR T-cell infusion neurotoxicity.
High-intensity chemotherapy during the bridging period did not appear associated with a higher rate of successful CAR T-cell infusion compared with low-intensity chemotherapy (63% vs. 79%), nor was it associated with increased success for the combined endpoint of CAR T-cell infusion or alternative therapy, including transplant (80% vs. 86%).
Results showed lower rates of severe CRS (0% vs. 41%; P = .01) or neurotoxicity (0% vs. 55%; P < .01) among patients in both groups who converted from morphologic to molecular disease during the bridging period (n = 9) compared with patients with persistent morphologic disease.
“This makes sense, as the patients in our trial were heavily treated and chemotherapy refractory and, fundamentally, very few patients had a significant response to the bridging therapy,” Perica said. “High-intensity therapy, however, was associated with a higher rate of severe grade 3 or grade 4 infectious complications, which can be life threatening and at the very least can potentially delay treatment with CAR T cells, and so we sound a note of caution about the use of aggressive therapy in the bridging period.”
Perica told HemOnc Today that his group’s study is limited by its nonrandomized, retrospective, single-center nature, but that the results mirror his clinical experience.
“Most patients require some therapy, but they are often better suited to a low-intensity regimen. ... The goal of bridging therapy is to keep the patients safe and stable until CAR T-cell infusion. In theory, if the tumor burden can be reduced before CAR T cells can be infused, this may lead to some benefits, and in the rare patients who did have a response to bridging that decreased their disease burden, we saw very little CRS or neurotoxicity,” he said.
“If CARs are moved to earlier lines where patients are less chemotherapy-resistant, there may be a role for high-intensity bridging chemotherapy, but the benefit of chemotherapy should be weighed against the potential risks for infection and worsening performance status, and careful consideration should be given when selecting appropriate bridging therapy for patients awaiting CAR T-cell infusion,” he added. – by Drew Amorosi
References:
Perica K, et al. Abstract 2520. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Park JH, et al. New Engl J Med. 2018;doi:10.1056/NEJMoa1709919.
Disclosures: Perica reports royalties from technology licensed to NexImmune Inc. Please see the abstract for all other authors’ relevant financial disclosures.