Second-Line Liso-cel Shows Promise in High-Risk Relapsed/Refractory FL

Franck Morschhauser, MD, PhD

Lisocabtagene maraleucel (liso-cel; Breyanzi) led to high complete response rates with durable remissions when given to patients with high-risk relapsed/refractory follicular lymphoma (FL) in the second line, according to updated findings from the TRANSCEND FL trial (NCT04245839).

In a poster presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition by Franck Morschhauser, MD, PhD, patients with FL receiving the CD19-targeted chimeric antigen receptor (CAR) T-cell therapy liso-cel had a duration of response (DOR) of 89.8% and a progression-free survival (PFS) of 91.3% at 12 months. With median follow-ups of 16.8 months and 17.8 months, the median DOR and PFS were not reached.

For safety, the most common grade ≥ 3 treatment-emergent adverse events included cytopenias, with neutropenia being most frequent in 52% of patients. A total of 12 patients (52%) had cytokine release syndrome (CRS), but none were grade 3 or greater. Further, the median times to onset and resolution of CRS were 6 days (range, 2-9) and 3 days (range, 2-7), respectively.

Neurological events were observed in 4 (17%) patients, with 1 (4%) being grade 3. None were deemed grade 4-5. The median times to onset and resolution of neurological events were 8.5 days (range, 6-11) and 2.5 days (range, 1-4), respectively. Tocilizumab (Actemra) or steroids were given to 13% of patients for CRS or neurological events.

According to Morschhauser, professor, hematology, University of Lille and Hospital Claude Huriez, and chair, Lymphoma Study Association (LYSA), longer follow-up remains to be done.

In an interview with Targeted Oncology^TM, Morschhauser discussed the high complete response rates and durable remissions seen with liso-cel in patients with high-risk relapsed/refractory FL.

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Targeted Oncology: Can you explain the background of TRANSCEND FL and what data were presented on at ASH 2023?

Morschhauser: This abstract was about the results of the TRANSCEND FL study in patients with relapsed or refractory follicular lymphoma in the second line with high risk for transplant. It was a pivotal multi-cohort trial evaluating liso-cel, a CD19 CAR T-cell [therapy], in relapsed or refractory follicular lymphoma. There are multiple lines of therapy out, but we have presented the results of the primary analysis [looking at the] efficacy and safety of the third line plus patients. Here at ASH, we wanted to focus on the second-line patients. This is the first time ever that we have reported efficacy and safety data in this particular group of patients.

Who was included in the trial? What were the main findings?

It is important to keep in mind that we have selected second-line patients with high-risk factors, namely progression of disease within 24 months of diagnosis and initiation of a first line with an anti-CD20 plus an alkylating regimen [at] 6 months of diagnosis [as the] first factor. The second factor was the possibility of having a high tumor burden. For those patients, we have recruited 25 patients, [and] 23 have received liso-cel with a conforming product. Among those patients, the overall response rate was extremely good and all the patients that achieved response achieved a complete response.

We also had durable responses, and the median are not reached for the duration of response, the median progression-free survival, and overall survival. Safety was also important because we had a majority of grade 1 or 2 CRS, but no grade 3, 4, or 5, which is important for the CAR T. In terms of neurological events, we had 70% and only 1 grade 3 that resolved within 2 days. Altogether, [it is] a promising, efficient, and safe treatment for [these patients].

What are the key points a community oncologist should take away from this research?

We have a response rate of 96%, [and] all the patients achieved complete response. The progression-free survival at 12 months was very high, around 82%, and all patients but 1 were alive at 12 months, which is a reasonable time to evaluate this patient given the data cutoff. We need longer follow-up but so far, this looks very promising.

How should clinicians manage the adverse events that might be seen with this agent moving forward?

The main thing we look at with CAR T cells is neurological levels. Here, even if the incidence was 52%, since it was mainly grade 1 or 2, the use of therapy against CRS and neurological events was low. Altogether, only 13% of the patients required either tocilizumab or steroids to control the CRS and neurological ailments. I think most of the patients are now used to that. Knowing the fact that most of them were low-grade and easily manageable is reinforcing confidence in the product.

What are the next steps for evaluating this agent?

Now, we need a third phase 3, randomized trial to confirm the results obtained in this small phase 2 cohort. The next step will be to have a phase 3 randomized trial comparing liso-cel to the standard-of-care in patients with second-line relapsed/refractory follicular lymphoma with POD24. First, the standard-of-care will be either R-CHOP [rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone] or R2 [lenalidomide plus rituximab], but there will be an additional cohort evaluating the benefits.

What are some advancements in this space that you are excited to see?

What seems to be moving to the first-line in follicular lymphoma and in diffuse large B-cell lymphoma are the bispecifics. There will be a large, phase 3, randomized trial evaluating the addition of bispecific antibodies through either chemotherapy for diffuse large B-cell lymphoma [DLBCL], or R-CHP [rituximab, cyclophosphamide, doxorubicin, and prednisone] or [polatuzumab vedotin (Polivy)]-R-CHP. In the follicular lymphoma space, it's more in addition with lenalidomide. We will see if this combination is worse, or is able to beat the conventional immunochemotherapy.

We also have another randomized trial in DLBCL evaluating the early onset, in a randomized fashion, of CAR T-cell [therapy] after 1 cycle of R-CHOP in [international prognostic index] 4-5 against conventional treatment with R-CHOP. These are, to me, the 2 most important things in the first-line setting. We also have important data coming with other CAR T-cell [therapies], in the [natural killer] space, or the allogeneic CAR T.

REFERENCE:

Morschhauser F, Dahiya S, Palomba ML, et al. TRANSCEND FL: Phase 2 study primary analysis of lisocabtagene maraleucel as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. Presented at: 2023 ASH Annual Meeting & Exposition, December 9-12; San Diego, California. Abstract 602.