Lisocabtagene maraleucel in follicular lymphoma: mysterious study discontinuation

The CAR T-cell preparation lisocabtagene maraleucel is approved for the treatment of adults with relapsed or refractory follicular lymphoma who have already undergone two or more lines of systemic therapy. In an early benefit assessment, the German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined whether CAR-T cells offer an added benefit to those patients.

The Federal Joint Committee ( G-BA) has defined an individualized treatment with a choice of six options as an appropriate comparator therapy. However, the manufacturer did not present any relevant study data. IQWiG therefore concluded that an added benefit of lisocabtagene maraleucel in comparison with the appropriate comparator therapy was not proven.

Submitted data unsuitable

On the one hand, the dossier contains data from the single-arm pivotal study without a comparison with other therapies in the therapeutic indication. On the other hand, the manufacturer presents an analysis that cannot be interpreted for several reasons: It is potentially incomplete, methodologically inadequate and contains no results on patient-relevant outcomes.

It is noteworthy that the manufacturer started a randomized controlled trial (RCT) in which lisocabtagene maraleucel was to be compared with one of the relevant comparator options, among other things. However, the trial was discontinued for reasons that are unclear.

It remains open which therapy option is best

"The manufacturer gives no reason for discontinuing the RCT," says Philip Kranz, head of the Haemato-Oncology and Infectiology Division in IQWiG’s Drug Assessment department. "That is regrettable. As although there are now a good handful of treatment options available, it is still unclear which one is best for those affected. In the discontinued RCT, at least two of the options would have been directly compared with each other.”

The G‑BA decides on the extent of the added benefit

The dossier assessment is part of the early benefit assessment in accordance with the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G‑BA. After publication of the dossier assessment, the G‑BA conducts a commenting procedure and makes a decision on the extent of the added benefit.