Encouraging Data Emerge for Outpatient CAR T-Cell Treatment of Lymphoma

Outpatient administration of chimeric antigen receptor (CAR) T-cell therapy has been touted as an avenue to expand access to this potentially lifesaving cancer treatment, but there has been less evidence on the safety and feasibility of outpatient vs inpatient delivery. Now, new results presented at the 2024 European Hematology Association Congress show data that may help encourage outpatient administration of CAR T-cell therapy for 2 types of lymphomas.

New results presented at EHA 2024 show data that may help encourage outpatient administration of CAR T-cell therapy for 2 types of lymphomas. | Image Credit: © C Davids/peopleimages.com - stock.adobe.com

Axi-Cel for Large B-Cell Lymphoma in ZUMA-24

In one of the abstracts, investigators presented data on patients with relapsed/refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel) in the outpatient setting after at least 1 prior line of therapy as part of the ZUMA-24 trial (NCT05459571).¹ After receiving a prior anti-CD20 monoclonal antibody and anthracycline-containing regimen, patients then underwent leukapheresis, lymphodepleting chemotherapy, optional bridging therapy, and a single axi-cel infusion. Patients also received prophylactic oral dexamethasone prior to and on the 2 days following axi-cel infusion, and all patients were monitored for adverse events (AEs) daily in the outpatient setting.

Among the 20 patients who received axi-cel, the median age was 59 years (range, 24-76), 70% were male, 25% had ECOG 1 disease, and 90% had received 1 prior line of chemotherapy. The median follow-up time was 5 months (range, 1-13).

Cytokine release syndrome (CRS) and neurologic events are of particular concern with CAR T-cell therapy, and they were observed in 85% and 75% of this cohort, respectively; grade 3 or higher CRS and neurologic events were seen in 5% and 25%. Median duration of CRS was 5 days (95% CI, 3-7) and of neurologic events was 8 days (95% CI, 3-32). More broadly, all patients experienced AEs of any grade, and 80% experienced severe AEs, although none were classified as grade 5. Ninety percent were hospitalized at any time after axi-cel infusion, and the most common cause was CRS, both in the 72 hours and the 7 days following infusion.

CAR T responses were similar to those seen in prior studies, with an overall response rate of 90% (95% CI, 68.3%-98.8%) and a complete response rate of 70% (95% CI, 45.7%-88.1%). The researchers noted that the duration of first hospitalization (median, 8 days) and rate of intensive care unit admission (10%) both compared favorably with those seen in prior clinical trials of axi-cel, “suggesting that outpatient administration of axi-cel may be safe and feasible.”

Presenting author Olalekan O. Oluwole, MD, of Vanderbilt University Medical Center, told The American Journal of Managed Care^® (AJMC^®) that outpatient administration of CAR T could help expand access not only by freeing up inpatient beds—“especially as we are treating more CAR T patients, we will run out of hospital beds”—but also because “quality of life is better outside the hospital than in the hospital.”

“I’m excited about these results, because it is as good as it was with ZUMA-1, actually maybe even safer because we are monitoring more closely,” he continued.

Axi-Cel or Brexu-Cel for Non-Hodgkin Lymphoma in the Real World

In another abstract, investigators report real-world outcomes after outpatient administration of axi-cel or brexucabtagene autoleucel (brexu-cel) to patients with R/R non-Hodgkin lymphoma at the Mayo Clinic in Rochester, Minnesota.² Among 155 patients treated in either the inpatient or outpatient settings from 2018 to 2022, the median age was 60 years, 64% were male, and 84% had LBCL; 139 (90%) received outpatient infusion of either CAR T-cell therapy (axi-cel, 94%; brexu-cel, 6%). Most (68%) had received more than 2 prior lines of therapy, and 39% had previously received stem cell transplant.

Within 30 days of CAR T infusion, the CRS rate was 81%, with just 4% experiencing CRS of grade 3 or higher, and the rate of immune effector cell–associated neurotoxicity syndrome (ICANS) was 55% (19% grade ≥3). The rates of these events did not significantly differ between the those treated with an early toxicity management strategy informed by ZUMA-1 trial findings³ (November 2021-December 2022) vs a late management strategy used prior to those findings (January 2018-October 2021). However, median time to CRS resolution was shorter with the early management approach (4.5 vs 6 days; P = .009), and fewer patients receiving early vs late management were hospitalized within 3 and 30 days of infusion (3 days: 29% vs 44%; P = .102; 30 days: 77% vs 89%; P = .067).²

The investigators noted that elevated lactate dehydrogenase levels 5 days prior to infusion were linked with higher odds of grade 3 or higher CRS/ICANS within 30 days of infusion (OR, 3.0; 95% CI, 1.2-7.9), and the 65% of patients who received bridging therapy also had increased odds of hospitalization within 3 days of infusion (OR, 3.2; 95% CI, 1.4-7.3).

After median follow-up times of 16.5 months in the early management period and 41.0 months in the late management period, the best overall response rate was 88% and 75% in each period, respectively, with complete response rates of 84% and 58%. In the early management period, median duration of response, progression-free survival, and overall survival were not reached, whereas in the late management period they were 12.9, 4.2, and 22.5 months, respectively.

“These results provide further evidence that [outpatient] administration of axi-cel and brexu-cel is feasible without added toxicity for [patients] with R/R [non-Hodgkin lymphoma], especially with earlier toxicity [management],” the researchers concluded.

Although this research was conducted within Mayo Clinic, outpatient CAR T administration is still doable for centers without as much experience or resources, presenting author Radhika Bansal, MBBS, of Mayo Clinic, told AJMC. “Any center who is wanting to set up an outpatient practice should first of all build their framework, then train their people in that framework, and then launch it. Any new beginning is difficult, but it is possible, and it will just require a lot of patience initially,” she said.

She also emphasized the need for research to further improve outpatient practice, including by better reaching the patients who are most likely to require additional care for adverse events. “We have predictive modeling, you can use clinical biomarkers, you can use digital tools like remote patient monitoring, wearable devices, you can use the community paramedics, and now with [artificial intelligence], the sky’s the limit.”

References

1. Leslie L, Baird J, Flinn IW, et al. ZUMA-24 preliminary analysis: a phase 2 study of axicabtagene ciloleucel in the outpatient setting with prophylactic corticosteroids in patients with relapsed/refractory large B-cell lymphoma. Poster presented at: European Hematology Association 2024 Congress; June 13-16, 2024; Madrid, Spain. Poster P1159.

2. Bansal R, Hsu H, Paludo J, et al. Updated trends in real-world outpatient (OP) administration of axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) in relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Poster presented at: European Hematology Association 2024 Congress; June 13-16, 2024; Madrid, Spain. Poster P1191.

3. Topp MS, van Meerten T, Houot R, et al. Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021;195(3):388-398. doi:10.1111/bjh.17673