Outpatient treatment with lisocabtagene maraleucel had consistent efficacy and safety with that of a previously reported clinical trial involving patients who were treated at university medical centers, according to results of 3 studies reported at the 2020 Transplantation & Cellular Therapy Meetings in Orlando, Florida.
Carlos R. Bachier, MD
Carlos R. Bachier, MD
Evaluation of lisocabtagene maraleucel (liso-cel) infusion and toxicity monitoring in the outpatient setting for the treatment of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) suggested feasibility of this approach, potentiating wider use of chimeric antigen receptor T-cell therapy in this disease.1Outpatient treatment had consistent efficacy and safety with that of a previously reported clinical trial involving patients who were treated at university medical centers, according to results of 3 studies reported at the 2020 Transplantation & Cellular Therapy Meetings in Orlando, Florida.
Evaluation of 44 patients treated as outpatients in the TRANSCEND NHL 001 (NCT02631044), PILOT (NCT03483103), and OUTREACH (NCT03744676) clinical trials showed that rates of cytokine release syndrome (CRS) and neurological events were similar to rates reported in all patients treated on TRANSCEND NHL 001 (n = 269), which was composed of patients treated in both inpatients and outpatient settings. There were no grade 5 treatment-emergent adverse events (AEs) reported in patients monitored as outpatients.1
“Most of the grade 3 or higher toxicities were related to myelosuppression as is expected in patients who receive lymphodepletion and CAR T-cell therapies,” Carlos R. Bachier, MD, director of Cellular Research at Sarah Cannon, said during the presentation. Rates of these events “were similar to what was previously reported in TRANSCEND [NHL] 001.”
Any-grade and grade ≥3 CRS and neurological events occurred in 45% and 5% of patients treated as outpatients, respectively, which was similar to rates observed in TRANSCEND (47% and 11%). Tocilizumab or corticosteroids were used in 11% of outpatients and 20% of patients on TRANSCEND. Corresponding rates of grade ≥3 infections (16% versus 12%) and prolonged grade ≥3 cytopenias (20% versus 37%) were similar between groups.
Median onset of CRS and neurological events in all outpatients (5 and 8 days, respectively) was similar to TRANSCEND for in/outpatients (5 and 9 days). Median duration of CRS was 6 days for outpatients and 5 days for TRANSCEND; neurological events occurred for a median of 16 and 11 days, respectively.
Forty-five percent of outpatients were not hospitalized, and only 5% were admitted to the intensive care unit after liso-cel administration. The median time to hospitalization was 5 days (range, 2-22), with patients staying for an average of 6.5 days. Reasons for hospitalization included CRS or neurological events in 14 patients (32%) and other AEs in 10 (23%).
Similarly, comparing efficacy for outpatient and TRANSCEND cohorts revealed no major differences in objective response rate (80% vs 73%, respectively). Complete and partial responses were observed in 55% and 25% of patients treated as outpatients, respectively; this compared with 53% and 20% of all patients on TRANSCEND. Rates of stable disease (7% vs 11%) and progressive disease (11% each) were comparable.
Baseline characteristics in all patients treated in the outpatient setting included a median age of 62 years (range, 24-82), with 41% being ≥65 years. The majority of patients had diffuse large B-cell lymphoma (61%). Thirteen (30%) patients had previously received stem cell transplant and 28 (64%) were refractory to chemotherapy, with the median number of prior therapies at 2 (range, 1-5). High tumor burden and lactate dehydrogenase ≥500 U/L was observed in 14% and 27% of patients, respectively.
Liso-cel is an investigational CD19-directed, 4-1BB CAR T-cell therapy that is administered at targeted doses of CD4+ and CD8+ CAR-positive T cells. Across the clinical program for liso-cel, outpatient treatment is allowed at the discretion of the treating physician with standardized guidelines for toxicity and safety monitoring.
Basic study designs for liso-cel include leukapheresis, optional bridging therapy during CAR T cell manufacturing, lymphodepletion, CAR T-cell therapy administration, and treatment follow-up. Patients treated on all 3 trials evaluated had to meet criteria for inclusion, such as age ≥18 years, left ventricle ejection fraction ≥40%, creatinine clearance ≥30 mL/min, levels of aspartate and alanine aminotransferase ≤ 5 × the upper limit of normal, and oxygen saturation ≥92%.
Centers that participated in the 3 trials had to be capable of either administering transplant or phase I trials, have an outpatient infusion center and an affiliated apheresis center, and have a multidisciplinary team equipped to treat patients receiving therapy. For toxicity management, patients had to have access to at least 1 hospital capable of treating AEs associate with CAR T-cell therapy with subspecialty care for neurology, cardiology, and infectious disease. Tocilizumab also had to be available in the pharmacy. Patients needed to stay within 1 hour of the monitoring facility within the first 30 days, with all patients and caregivers receiving safety monitoring education to be able to recognize the effects of CRS and neurologic events.
“There was extensive education given to patient and caregiver for recognizing the early symptoms of CRS and neurological events, with a commitment to return at the onset of potential adverse effects,” Bachier said.
Outpatient monitoring involved daily clinic visits or phone calls for the first 7 days, then at least twice per week until 30 days.
Traditionally, CAR T-cell therapy has typically been limited to inpatient treatment at academic centers due in large part to infusion and toxicity monitoring. This contrasts with that fact that most patients with R/R LBCL treated in the United States receive their therapy at outpatient infusion centers.
At the 62nd Annual American Society of Hematology Annual Meeting, results of the multicenter phase I TRANSCEND NHL 001 trial were reported and showed that high rates of rapid and durable responses occurred with the use of liso-cel in patients with R/R LBCL following ≥2 prior therapies. Low incidences of both CRS and neurological events were reported at that time, with investigators noting that this supports the potential for use in the outpatient setting.2
“Infusion and monitoring of patients receiving CAR T-cell therapy in the outpatient setting may lead to wider utilization and improved access [to care],” Bachier concluded.