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Outpatient administration of liso-cel: Preliminary results from the OUTREACH study

Apr 1, 2021
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Due to concerns regarding adverse events (AEs), chimeric antigen receptor (CAR) T-cell therapies are predominantly given as inpatient treatments in university medical centers in the U.S. However, the necessity of this limitation, and the safety of administering CAR T-cell therapies in outpatient and nonuniversity settings, has not yet been examined.

During the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), John Godwin presented preliminary data from the OUTREACH study (NCT03744676), an open-label, multicenter, phase II study of safety and efficacy outcomes of lisocabtagene maraleucel (liso-cel) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) in nonuniversity inpatient and outpatient settings in the U.S. We are pleased to report a summary of the findings here, which expand upon the initial results previously covered on the Lymphoma Hub.

Study design

Following lymphodepletion with fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 for 3 days, adults with R/R LBCL received liso-cel at 100 × 106 CAR T cells, 2–7 days after lymphodepletion, either as inpatients or outpatients at nonuniversity medical centers.

Eligible patients had R/R positron emission tomography (PET)-confirmed disease after ≥2 lines of therapy, Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, and adequate organ function. Prior autologous hematopoietic stem cell transplants (HSCTs) were permitted, as were secondary central nervous system lymphomas.

Primary endpoints were incidences of Grade ≥3 cytokine release syndrome (CRS), neurologic events (NEs), prolonged cytopenias, and infections. Secondary endpoints included AEs, overall response rate (ORR), and complete response (CR) rate.

Patients

Of the 46 patients enrolled, 43% and 50% of outpatients and inpatients, respectively, were aged ≥65 years. Patient characteristics in both settings are shown in Table 1.

Table 1. Characteristics of patients enrolled in outpatient and inpatient settings1

Outcome

Outpatients
(n = 30)

Inpatients
(n = 16)

Median age, years (range)

63 (35–83)

65 (34–81)

Male, %

70

63

Ethnicity, %
              Hispanic/Latino
              Not Hispanic/Latino


13
73


19
75

Histology, %
              DLBCL NOS
              DLBCL transformed from indolent histologies
              HGBCL/PMBCL/FL3B


63
30
7


63
0
38

ECOG PS ≤1, %

100

100

Median prior lines of therapy, n (range)

2 (2–4)

2 (2–6)

Prior HSCT, %

27

6

Chemotherapy refractory, %

83

88

DLBCL, diffuse large B-cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group performance status; FL3B, follicular lymphoma Grade 3B; HGBCL, high-grade B-cell lymphoma; HSCT, hematopoietic stem cell transplant; NOS, not otherwise specified; PMBCL, primary mediastinal large B-cell lymphoma.

Key findings

Safety

The most common treatment-emergent AEs (TEAEs) in outpatient and inpatient settings were neutropenia, leukopenia, and anemia. Cytopenias were less frequent in outpatients versus inpatients (neutropenia, 57% vs 94%). Table 2 lists TEAEs of special interest. No cases of CRS Grade ≥3 were reported in either setting, and incidences of Grade ≥3 NEs were similar. Infections and prolonged cytopenias of Grade ≥3 were more frequent in outpatients than inpatients. The use of tocilizumab with or without corticosteroids for the management of CRS (13%) and NEs (11%) was low.

Table 2. AEs of special interest reported in outpatient and inpatient settings1

AE

Outpatients
(n = 30)

Inpatients
(n = 16)

CRS
              Any grade, %
              Grade ≥3, %
              Median time to onset, days (range)


43
0
5 (2–9)


38
0
2.5 (1–3)

NE
              Any grade, %
              Grade ≥3, %
              Median time to onset, days (range)


30
7
9 (6–14)


31
6
10 (3–16)

Prolonged cytopenia Grade ≥3, %*

30

13

Infection Grade ≥3, %

17

6

AE, adverse event; CRS, cytokine release syndrome; NE, neurological event.
*Based on laboratory assessments of neutropenia, thrombocytopenia, or anemia unresolved at Day 29.

Hospitalization was required for 19 outpatients (63%) after a median time of 5 days (range, 2–61); 16 of these were due to AEs. One outpatient was admitted to intensive care following liso-cel administration.

Efficacy

After a median follow-up of 6.7 months (range, 0.4–16.0), efficacy outcomes were similar between outpatients and inpatients (Figure 1). Durable responses were observed, with ongoing CRs noted in 92% of patients with ≥6 months of follow-up data available.

Figure 1. Best overall response with liso-cel treatment in outpatient and inpatient settings1 

CR, complete response; PR, partial response.

Conclusion

In this study of patients with R/R LBCL, administration of liso-cel and monitoring of CAR T-cell therapy-related toxicities was feasible and effective in outpatient settings in nonuniversity medical centers, in addition to inpatient treatment. Incidences of severe CRS and NEs were low in both settings, with similar ORR and CR rates.

The authors therefore concluded that it is safe to provide liso-cel treatment in outpatient settings and nonuniversity centers, which will provide greater convenience and accessibility for patients.

  1. Godwin JE, Maris M, Stevens DA, et al. Outcomes of treatment with the chimeric antigen receptor (CAR) T cell therapy lisocabtagene maraleucel (liso-cel) in the nonuniversity setting: initial results from the OUTREACH study. Oral Abstract #OS2-6. 47th Annual Meeting of the EBMT; Mar 14, 2021; Virtual.

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