ORLANDO, Florida Chimeric antigen receptor (CAR) T-cell therapy can be safely delivered in the outpatient setting, which could make the life-extending treatment available to patients who don't have access to a major teaching hospital or treatment center, contend investigators who analyzed data from three clinical trials.
Looking at outcomes for patients with large B-cell lymphomas (LBCL) who were treated with the CAR T-cell construct lisocabtagene maraleucel (liso-cel) in the outpatient setting at both university-based and nonacademic medical centers in three clinical trials, Carlos Bachier, MD, from the Sarah Cannon Blood Cancer Network in Nashville, Tennessee, and colleagues found that the incidences of severe adverse events were relatively low and manageable.
"Outpatient administration of liso-cel and subsequent monitoring were successfully implemented in multiple clinical trials at both university and nonuniversity sites," he said here at the Transplantation and Cellular Therapy annual meeting.
Dr Carlos Bachier
The need to monitor and treat serious side effects from CAR T therapy, such as the cytokine release syndrome (CRS) and neurologic toxicities, has previously limited the therapy to major treatment centers with extensive resources. Yet most patients in the US with relapsed or refractory large B-cell non-Hodgkin lymphoma are treated at nonacademic centers where cancer therapies are typically delivered in outpatient infusion centers, Bachier said.
"Infusion and monitoring of patients receiving CAR T-cell therapy in the outpatient setting can lead to wider utilization and improved access," he said.
To get a better idea of the safety and efficacy of CAR T-cell therapy in the outpatient setting, Bachier and colleagues examined outcomes from the phase 1 TRANSCEND NHL 001 trial of liso-cel in one or two doses for a variety of aggressive lymphoma histologies, conducted in both university-based and nonuniversity centers; the phase 2 TRANSCEND-OUTREACH trial of outpatient liso-cel therapy after two or more prior lines of therapy against various lymphomas and lymphoproliferative disorders, conducted in nonuniversity centers; and the phase 2 TRANSCEND-PILOT-017006, testing liso-cel in patients with LBCL relapsed or refractory after a single line of immunochemotherapy who were ineligible for either high-dose chemotherapy or stem cell transplant. This trial was conducted in both university and nonuniversity settings.
In OUTREACH and PILOT, liso-cel was administered at a dose of 100 x 106 CAR-positive T cells; in TRANSCEND, it was given at doses of 50, 100, or150 x 106.
To qualify for outpatient administration and monitoring, both university centers and nonuniversity specialty oncology centers had to have at least hematopoietic stem cell therapy (HSCT) or phase 1 trial capability, an outpatient infusion center or inpatient infusion unit with same-day discharge; an affiliated aphereseis center; and a multidisciplinary medical team that can coordinate care between inpatient and outpatient settings, have standard operating procedures for outpatient monitoring and admissions when necessary, and an oncologist on call at all times.
In addition, each center had to have one designated hospital for care of CAR T-cell recipients with staff trained to manage typical CAR T-cell toxicities and a ready supply of tocilizumab (Actemra, Genentech) for treating CRS.
For their part, patients needed to have caregiver support and stay within 1 hour travel of the treatment center for the first 30 days after infusions, had to commit to returning to the site for immediate medical evaluation as necessary, and had to be educated about the early signs and symptoms of CRS and neurologic toxicities.
The analysis included data on 44 patients with a median age of 62 years (range 24 to 82), including 25 enrolled in TRANSCEND, 13 in OUTREACH, and 6 in PILOT. Eighteen patients were age 65 or older, 12 had high tumor burden, and 6 had lactate dehydrogenase (LDH) levels of 500 U/L or higher.
Treatment-related adverse events (TEAEs) occurring in at least 25% of outpatients were similar to those among all patients in TRANSCEND, with the most frequent grade 3 or 4 events being neutropenia, anemia, and thrombocytopenia. There were no treatment-related deaths among those monitored as outpatients.
CRS of any grade occurred in 12 of 25 outpatients (48%) in TRANSCEND, in 5 of 13 (38%) in OUTREACH, and in none of the 6 outpatients in PILOT. Grade 3 or 4 CRS was seen in 1 outpatient in TRANSCEND, but in none of the other patients in the other two trials.
Grade 3 or 4 neurologic events occurred in two outpatients in TRANSCEND, but were not seen in any outpatients in OUTREACH or PILOT.
Three patients in TRANSCEND and two in OUTREACH received either tocilizumab or corticosteroids for CRS, and five patients in TRANSCEND received corticosteroids for neurologic adverse events. Prolonged grade 3 or greater cytopenias were seen in three patients in TRANSCEND, five in OUTREACH, and one in PILOT.
The median onset of CRS was 5 days, and the median onset of neurologic toxicities was 8 days among all outpatients, and was similar to combined inpatient and outpatient population in TRANSCEND. The median duration of the events 6 days for CRS, 16 days for neurologic events was also similar to that seen in TRANSCEND.
Of the 44 patients from all three trials, 24 (55%) were hospitalized after liso-cel administration, for a median of 6.5 days (range 2-23). The median time to hospitalization was 5 days. One third of the hospitalizations were for either CRS or neurologic events. There were 2 cases of ICU admissions after liso-cel administration, for a median ICU stay of 4 days.
In all, 45% of outpatients did not require hospitalization, and there was no increase in ICU admissions compared with inpatients, Bachier pointed out.
The overall response rate was 80%, with a complete response rate of 55%, similar to that seen in TRANSCEND, he said.
In an interview with Medscape Medical News seeking objective commentary on the findings, Yago Nieto, MD, from the University of Texas MD Anderson Cancer Center in Houston, said that he would be comfortable with CAR T-cell therapy in the outpatient setting, provided that several key components of care are in place.
"It requires an organized effort to be able to see those patients in an outpatient clinic weekdays and weekends, having every contingency discussed beforehand, including for ICU team members to admit patients into the ICU if necessary which is unusual, particularly with liso-cel but it has to be all worked out in advance in a multidisciplinary effort," he said.
Nieto comoderated the session where the data were presented, but was not involved in the study.
Comoderator Mazyar Shadman, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, who was not involved in the study, told Medscape that his center treats patients with CAR T therapy in the outpatient setting.
"But it's important to know that when you talk about outpatient care, it's not your outpatient clinic where you see patients once a week," he said. "These are intensive outpatient centers. We have a team that's just outpatient, but we see these patients on a daily basis, we have dedicated nurses and practitioners, and we have labs and immunotherapy services for getting results quickly."
"I feel comfortable giving CAR T therapy to a patient in this setting," he added, "but not to a patient being treated in the middle of nowhere."
The study was funded by Juno Therapeutics, a Bristol-Myers Squibb company. Bachier disclosed advisory board activities for various companies, not including Juno or BMS. Nieto disclosed research funding and consultancy for various companies not including the sponsors of this study. Shadman disclosed research funding, honoraria, and consultancy with various companies not including Juno or BMS.
Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR 2020: Abstract29. Presented February 19, 2020.
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