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CAR-T Meeting 2022 | Moving CAR-Ts from third-line to second-line in NHL

Christian Chabannon, MD, PhD, Institut Paoli Calmettes, Marseille, France, discusses whether chimeric antigen receptor T-cell (CAR-T) therapy is going to become the new standard of care (SOC) for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) in the second-line setting. Three ongoing clinical trials, ZUMA-7 (NCT03391466), TRANSFORM (NCT03575351) and BELINDA (NCT03570892) comparing CAR-T therapies versus the current SOC consisting of salvage chemotherapy and high-dose chemotherapy consolidation supported with autologous stem cell transplantation (ASCT) recently published preliminary data, and two out of three studies reported positive results. Nevertheless, Prof. Chabannon explains that these trials had very different designs and cannot be directly compared. In addition, although CAR-T therapy has many advantages over the current SOC, access to these new therapies is limited for various reasons. This interview took place at the EBMT-EHA 4th European CAR T-cell Meeting which was held virtually in 2022.

Transcript (edited for clarity)

The short answer to this question is yes, obviously this has become standard of care for patients with relapsed or refractory non-Hodgkin lymphoma after two lines of chemotherapy. And this is part of the marketing approval for the currently approved product on the European market. But the interesting question at the moment is whether actually CAR-Ts, autologous CAR-Ts that target the CD19 antigen, will move from third to second line...

The short answer to this question is yes, obviously this has become standard of care for patients with relapsed or refractory non-Hodgkin lymphoma after two lines of chemotherapy. And this is part of the marketing approval for the currently approved product on the European market. But the interesting question at the moment is whether actually CAR-Ts, autologous CAR-Ts that target the CD19 antigen, will move from third to second line. Meaning will patients with high-grade B-cell lymphoma be treated with CAR-Ts as soon as they experience their first relapse? And that was the topic of the debate with several of my European colleagues following a recorded presentation by Professor Mehdi Hamadani from the USA. And the question relates to the recently published results of three different randomized trials, comparing CAR-Ts targeting CD19 to what is currently considered a standard of care, meaning salvage chemotherapy and in chemosensitive patients consolidation with high-dose chemotherapy, supported with autologous transplantation.

And it was nice to remind that the concept of salvage chemotherapy and high-dose consolidation chemotherapy dates back to the PARMA study approximately 30 years ago, which by the way, was already a very small study. Multi-center international trial, randomized trial, but with very few patients in each arm and the conclusion of the study stand strong enough that they basically provided the basis for this standard of care for approximately three decades. It’s now being challenged. But again, the discussion stressed the fact that the three different studies, two of which are positive and one is negative, have different designs. It’s very difficult to compare the results of the three studies that the three different CAR-Ts that are evaluated in these three different studies were not compared head-to-head. So at the moment, it’s very difficult to conclude, and it’s important to stress that there is no marketing approval at the moment in Europe for CAR-Ts in second line.

One important aspect of course, is that standard of care is a multi-step process, including three or four cycles of salvage chemotherapy followed by high-dose consolidation therapy supported with autologous cell transplantation. So obviously this is a lengthy process for patients with a significant impact on quality of life. And at each step, a fraction of patients may drop out of the original therapeutic scheme for a variety of reasons. In comparison, CAR-Ts are a one-shot treatment, but access to CAR-Ts can be hampered by different reasons. Some of them being related to the patient’s condition, some of them being related to the nature of the tumor and the cause of the disease and some of them being related to the current organization for access to CAR T cells.

So there is no firm conclusion to this discussion. Again, CAR T cells are standard of care in third line in relapse and refractory B-cell NHL patients in third line. They may be moving in the future in second line once the healthcare authorities have decided on the strength of the three available studies.

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Disclosures

Honorarium from Bellicum Pharmaceuticals / BMS Celgene / Kite Gilead / Novartis / Janssen Pharmaceuticals