Liso-cel Maintains Efficacy in Outpatient Setting for Patients With Large B-Cell Lymphomas

The administration of lisocabtagene maraleucel (liso-cel) in the outpatient setting with subsequent monitoring was implemented successfully in multiple clinical trials at academic and nonacademic medical centers, and the efficacy and safety were consistent with that which has been seen in patients with large B-cell lymphoma in the inpatient setting, according to a poster presented during the 25th Annual European Hematology Association Congress.

The objective response rate (ORR) was 84% in the outpatient setting, which included 61% complete responses and 23% partial responses, compared with an ORR of 73% in the inpatient setting, which included 53% complete responses and 20% partial responses. Stable disease was observed in 5% of patients in the outpatient setting versus 11% in the inpatient setting, and progressive disease was noted in 11% of patients in each arm. Investigators will continue to monitor the administration of liso-cel in the outpatient setting for patients with large B-cell lymphomas.

This study aimed to evaluate the safety and efficacy of this chimeric antigen receptor (CAR) T-cell therapy in patients who were monitored in the outpatient setting in 3 separate clinical trials, including TRANSCEND NHL 001 (NCT02631044), TRANSCEND OUTREACH-007 (NCT03744676), and TRANSCEND-PILOT-017006 (NCT03483103). Patients treated in both academic and nonacademic centers were evaluated. Both TRANSCEND NHL 001 (n = 269) and TRANSCEND-PILOT-017006 (n = 29) included patients from academic and nonacademic centers, while TRANSCEND OUTREACH-007 (n = 34) only included patients from nonacademic medical centers. Overall, 25 patients from TRANSCEND NHL 001, 22 from TRANSCEND OUTREACH-007, and 12 from TRANSCEND-PILOT-017006 were included in the outpatient group for a total of 59 patients compared with 273 patients in the inpatient group.

Cytokine release syndrome (CRS) and/or neurological events (NEs) were observed in 42% of patients, and the median time to onset was 5 and 8 days, respectively. Among those with CRS, 4 patients (7%) required treatment with tocilizumab and corticosteroids for CRS, and 7 patients (12%) required treatment for NEs with corticosteroids.

Hospitalization was not required in 46% of patients after the administration of liso-cel and 83% before study day 4. The median time to hospitalization was study day 5, and there were no increases in ICU-level care among patients in the study.

CRS and NEs were observed in 15 of 25 patients (60%) in the TRANSCEND NHL 001 trial, 10 of 22 (45%) in TRANSCEND OUTREACH-007, none in TRANSCEND-PILOT-017006, and 25 of 59 (42%) in the outpatient setting, and at least grade 3 CRS was seen in 2 patients (8%), 1 (5%), none, and 3 (5%), respectively. CRS or NEs of any grade or of at least grade 3 were observed in 124 patients (45%) and 29 patients (11%) of 272 in the inpatient arm, respectively.

CRS was noted as any grade or at least grade 3 in 12 (48%) and 1 (4%) in the TRANSCEND NHL 001 study, 9 (41%) and 0 in the TRANSCEND OUTREACH-007 study, 0 and 0 in the TRANSCEND-PILOT-017006 study, and 21 (36%) and 1 (2%) in the overall population, compared with 111 (41%) and 5 (2%) in the control arm, respectively.

NEs of any grade and at least grade in 11 (44%) and 2 (8%) in the TRANSCEND NHL 001 study, 6 (27%) and 1 (5%) in TRANSCEND OUTREACH-007, 0 and 0 in TRANSCEND-PILOT-017006, and 17 (29%) and 3 (5%) in the overall population compared with 75 (27%) and 27 (10%) in the control arm, respectively.

Infections of at least grade 3 were observed in 11 patients (19%) in the overall outpatient population versus 29 (11%) in the inpatient population. Prolonged cytopenias of at least grade 3 were observed in 12 (20%) of the patients in the outpatient group compared with 102 (37%) in the inpatient group.

In the outpatient setting, at least grade 3 treatment-emergent adverse events (AEs) occurring in at least 25% of patients included neutropenia, anemia, leukopenia, thrombocytopenia, CRS, decreased appetite, nausea, headache, hypertension, and diarrhea, all of which were observed in the inpatient setting, but only at least grade 3 fatigue and dizziness only occurred in the inpatient group.

No grade 5 treatment-emergent AEs were observed in the outpatient arm, and only 5 were reported in 3% of patients (8 out of 273). The most common of these events included cardiomyopathy, diffuse alveolar damage, leukoencephalopathy, multiple organ dysfunction syndrome, progressive multifocal leukoencephalopathy, pulmonary hemorrhage, septic shock, and sepsis/colorectal cancer.

Any grade treatment-emergent symptoms of CRS occurring in at least 2% of patients included pyrexia in 21 patients (36%) in the outpatient arm versus 106 (39%) in the inpatient arm, tachycardia in 11 (19%) versus 39 (14%), hypotension in 7 (12%) versus 52 (19%), chills in 4 (7%) versus 30 (11%), headache in 4 (7%) versus 13 (5%), fatigue in 3 (5%) versus 15 (5%), hypoxia in 3 (5%) versus 24 (9%), and nausea in 2 (3%) versus 7 (3%), respectively.

Any grade treatment-emergent symptoms of NEs also occurred in 11 patients (44%) from the outpatient arm and 75 (27%) in the inpatient arm, and at least grade 3 were observed in 2 patients (8%) in the outpatient arm and 27 (10%) in the inpatient arm. The most common of these symptoms in the outpatient versus inpatient arms included tremor in 7 patients (12%) versus 23 (8%), dizziness in 3 (5%) versus 10 (4%), mental status change in 2 93%) versus 8 (3%), agitation in 1 (2%) versus 9 (3%), aphasia in 1 (2%) versus 23 (8%), confusional state in 1 (2%) versus 32 (12%), somnolence in 1 (2%) versus 6 (2%), encephalopathy in 0 patients versus 18 (7%), and headache in 0 patients versus 7 (3%), respectively.

The most common grade 3/4 treatment-emergent CRS symptoms included headache (3%) and pyrexia (3%) in the outpatient group compared with hypotension (3%), hypoxia (3%), and pyrexia (2%) in the inpatient group. The most common grade 3/4 treatment-emergency NE symptoms were mental status change (3%), agitation (2%), and ataxia (2%) in the outpatient arm versus encephalopathy (4%) in the control arm.

Efficacy was assessed by positron emission tomography/computed tomography scans according to the 2014 Lugano criteria at 1, 3, 6, 9, 12, 18, and 24 months per Independent Review Committee in the TRANSCEND NHL 001 study or investigator assessment in the TRANSCEND OUTREACH-007 and TRANSCEND-PILOT-017006 studies. AEs were graded by the National Cancer Institute Common Terminology Criteria, while CRS was graded via the Lee et al criteria and NEs were defined by investigators as liso-cel-associated or -related events.

All patients from the 3 studies who had large B-cell lymphoma were included in the analysis regardless of the follow-up time. To be considered “outpatients” in this analysis, patients had to have received the liso-cel infusion in the outpatient or inpatient setting and leave or be discharged from the clinic at the end of the observation period on the day of infusion.

The median age of patients included in the analysis was 63 years (range, 24-83), and 35 (59%) were men. Thirty-eight patients (64%) had diffuse large B-cell lymphoma, 10 (17%) had diffuse large B-cell lymphoma transformed from indolent histologies, and 11 (19%) had HGBCL/PMBCL/FL3B. Fifty-six patients of the 59 patients in the analysis (95%) had an ECOG performance status of 0.

CAR T-cell therapy is generally administered in the inpatient setting with monitoring for side effects at academic medical centers, but many patients with relapsed or refractory large B-cell lymphoma receive therapy at nonacademic centers, which commonly administer cancer treatments in outpatient centers. The administration of CAR T-cell therapy in the outpatient setting may lead to widespread use and improved access to the treatment.

The CD19-direct CAR T-cell therapy liso-cel has demonstrated previous efficacy and safety in patients with relapsed/refractory large B-cell lymphoma in the TRANSCEND NHL 001 clinical trial, in which CRS and NEs occurred in 47% of patients, and the median time to onset was 5 and 9 days, respectively. At least grade 3 CRS or NEs were observed in only 2% and 10% of patients, respectively.

_Reference

_{Bachier C, Godwin J, Andreadis C, et al. Outpatient treatment with lisocabtagene maraleucel (liso-cel) across a variety of clinical sites from 3 ongoing clinical studies in relapsed/refractory (r/r) large b-cell lymphoma (LBCL). Presented at: 2020 European Hematology Association Virtual Congress; June 11-21, 2020. Accessed June 24, 2020. https://bit.ly/2Nra6Jt}