Outpatient CAR T-Cell Therapy Found Safe, Effective in Large B-Cell Lymphoma

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Partner | Cancer Centers | <b>Sarah Cannon Research Institute at Tennessee Oncology</b>

Carlos R. Bachier, MD, discusses the use of CAR T-cell therapy in the outpatient setting. He also shared insight on the evolving paradigm of graft-versus-host disease.

Carlos R. Bachier, MD

Administering CAR T-cell therapy in the outpatient setting is found to be safe and effective, according to an analysis of 3 studies evaluating lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory large B-cell lymphoma, explained Carlos R. Bachier, MD.

Results showed that outpatient treatment had comparable clinical outcomes and toxicity as treatment across all patients. In the TRANSCEND NHL 001 (NCT02631044), PILOT (NCT03483103), and OUTREACH (NCT03744676) studies, 44 patients who were treated in an outpatient setting demonstrated similar rates of cytokine release syndrome (CRS) and neurological events compared with all 269 patients who were treated in the TRANSCEND NHL 001 trial, which evaluated patients treated in both the inpatient and outpatient settings.

No grade 5 treatment-related adverse events (AEs) were reported in those treated in the outpatient setting. Any-grade and grade ≥3 CRS and neurological events occurred in 45% and 5% of those treated as outpatients, respectively, which closely resembled data from the TRANSCEND NHL 001 at 47% and 11%, respectively.

To address these AEs, tocilizumab (Actemra) or corticosteroids were used in 11% of outpatients and in 20% of patients overall in TRANSCEND NHL 001. The corresponding rates of grade ≥3 infections were 16% versus 12%; prolonged grade ≥3 cytopenia were 20% in the outpatient setting versus 37% of patients overall in TRANSCEND NHL 001.

“[CAR T-cell therapy] can be delivered in the outpatient setting safely,” said Bachier. “Currently, the 40 to 50 patients who have been treated in the outpatient setting suggest that this therapy can be delivered safely in the outpatient setting.”

In an interview with OncLive, Bachier, director of Cellular Research at Sarah Cannon Research Institute, discussed the use of CAR T-cell therapy in the outpatient setting. He also shared insight on the evolving paradigm of graft-versus-host disease (GVHD).

OncLive: Could you discuss this study examining liso-cel in the outpatient setting?

Bachier: CAR T-cell therapies are now approved for the treatment of patients with diffuse large B-cell lymphoma. There are 2 commercially approved products. Liso-cel is a CD19-directed CAR T cell that is going through the approval process. We're hopeful that the product will be available commercially either by the end of 2020 or 2021. This clinical trial looked at the possibility of administering CAR T cells in the outpatient setting.

CAR T cells [are associated with] AEs, including CRS and neurological events, such as immune effector cell—associated neurotoxicity syndrome. Different products have different degrees of incidence and severity for these potential AEs. It turns out that liso-cel has a relatively low incidence of AEs and they occurr relatively late compared with other products.

Due to these relatively low incidence of these AEs, the strategy was to attempt to deliver [liso-cel] in an outpatient setting. The [analysis] included patients from 3 different trials and looked at the outcomes of patients who were treated in the outpatient setting. Before these sites were able to treat patients in the outpatient setting, there was a vetting in the evaluation process to make sure that this could be safely done, including making sure that the clinics and the hospital had appropriate staff and training.

The results of the trial showed that [CAR T-cell therapy] was safe among patients treated in the outpatient setting. There were the expected AEs and if patients developed any of them, they were admitted to the hospital to be monitored. The response rates and the outcomes of these patients were comparable with patients who were treated in the inpatient setting. Based on this result, the indications are that you can deliver this therapy in the outpatient setting in a safe way with good outcomes that are similar as patients who are treated in the inpatient setting. Some of these trials are still accruing patients and we need to wait for more patients to be enrolled. Initial results suggest that [liso-cel] can be delivered safely in the outpatient setting.

The AEs are similar [with liso-cel] to what we see with other CAR T cells, including CRS, which is when the cells start attacking lymphoma cells. They can produce inflammation and produce cytokines that can lead to fevers, hypertension, respiratory problems, and neurological events, including confusion and seizures. The incidence and severity of these AEs with liso-cel have been relatively low compared with other products.

What is GVHD and how can it be avoided?

GVHD is an immunologic reaction to the donor T cells that can react against host tissues. These T cells are very similar to the T cells of the recipient, but they're not exactly the same. Therefore, the immune system of the recipient can recognize cells or organs of that recipient as foreign and cause an immune reaction. We now have strategies to prevent GVHD, with different drugs and manipulations of the [T-cell] product before it's infused. There are still patients who can develop these reactions in the target organs for GVHD, which are the skin, gastrointestinal tract, and liver—in the acute setting. The chronic setting, which has somewhat different features, can include other organs including the lungs, eyes, and oral mucosa.

In this meeting, there is a new drug that is called KD025. This drug helps the treatment of patients with steroid-refractory chronic GVHD and it has been quite effective. We're all excited that we may have another drug that can treat these complications that can be very difficult to manage. There are other strategies that are being evaluated in the acute setting and it's a very active area of investigation; we are developing new drugs and new strategies to treat patients with acute and chronic GVHD.

What is your experience with using ruxolitinib (Jakafi) to combat GVHD?

Ruxolitinib is in the family of JAK inhibitors, which is one of the areas that has been investigated [in this space]. Ruxolitinib is now approved for the treatment of patients with steroid-refractory acute GVHD and it's now being evaluated in other settings, including chronic GVHD. There are different types of JAK inhibitors, including itacitinib that is a selected JAK1 inhibitor being evaluated in chronic GVHD. It's an active drug that has been shown to be effective.

What is the safety profile of JAK inhibitors?

[JAK inhibitors] can cause myelosuppression. That's one of the important AEs that we need to monitor patients when we treat them for GVHD. Aside from that, it is a drug that is usually relatively well tolerated.

What is the future of GVHD treatment?

There are a number of strategies that are being developed with antibodies with other immune modulators. The list is significant, and they are all in different phases of development. The ones that we talked about are the ones that are a bit more advanced in the development.

This has been a very exciting conference. There is a lot of information and excitement within the immune-effector cell fields or CAR T cells. That is where a lot of the research and excitement is happening now in cell therapy.

Bachier CR, Palomba ML, Abramson JA, et al. Outpatient treatment with lisocabtagene maraleucel (liso-cel) in 3 ongoing clinical studies in relapsed/refractory (R/R) large B cell non-Hodgkin lymphoma (NHL), including second-line transplant noneligible (TNE) patients: TRANSCEND NHL 001, OUTREACH, and PILOT. 2020;26(3):S25-S26. doi: 10.1016/j.bbmt.2019.12.093