Public Release: 

Idelalisib in second-line treatment for CLL: Added benefit again not proven

Approval change due to complications / still no relevant data

Institute for Quality and Efficiency in Health Care

Already in 2014, the German Institute for Quality and Efficiency in Health Care (IQWiG) examined in an early benefit assessment whether idelalisib offers advantages over the appropriate comparator therapy for patients with chronic lymphocytic leukaemia (CLL). According to the findings, an added benefit was not proven because the drug manufacturer had presented no suitable data.

Due to the time limitation of the decision by the Federal Joint Committee (G-BA), IQWiG now presented a new assessment, which was conducted under changed circumstances: Following reports of severe complications and deaths, mostly due to respiratory tract infections, the European Medicines Agency (EMA) restricted the therapeutic indication in March 2016. Idelalisib may no longer be used to start first-line treatment. The drug is still approved for second-line treatment and for continuing first-line treatment that has already been initiated. Also in the new dossier assessment, the Institute concluded: An added benefit of idelalisib in comparison with the appropriate comparator therapy is not proven.

Three subindications with different treatment options

According to the approval, the G-BA distinguished between two subpopulations: on the one hand, patients with relapsed or refractory CLL who have received at least one prior therapy, and, on the other, patients with 17p deletion or TP53 mutation who are unsuitable for chemo-immunotherapy and who have already initiated treatment with idelalisib.

Depending on the treatment already initiated, the G-BA specified ibrutinib or best supportive care (BSC) as appropriate comparator therapy for the second group. The first group included patients for whom chemotherapy is indicated and patients for whom this is not the case. The appropriate comparator therapy was either chemotherapy optimized for the individual patient at the physician's discretion, preferably in combination with rituximab, or, again, ibrutinib or BSC.

No data submitted on two of three populations

Due to the ongoing risk assessment process at EMA, the manufacturer did not submit data from the continued first-line treatment. It also presented no data for the group with relapsed or refractory CLL for whom chemotherapy is indicated. An added benefit of idelalisib in comparison with the appropriate comparator therapies is therefore not proven for these two research questions.

As in its first dossier, the manufacturer submitted data from the studies GS-US-312-0116 and GS-US-312-0117 for patients with relapsed or refractory CLL for whom chemotherapy is not an option. As already explained in dossier assessment A14-35, these were unsuitable for the comparison with the appropriate comparator therapy. Additional data from the final data cut-off of one study and from an interim analysis of the other study, from which the manufacturer itself also derived no conclusions, also did not change this. Hence the manufacturer's conclusion on the added benefit was based on the same data as in 2014.

In the overall consideration, an added benefit of idelalisib is not proven for any of the subpopulations also in the modified therapeutic indication.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to 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 final decision on the extent of the added benefit.

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An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the Website gesundheitsinformation.de, published by IQWiG, provides easily understandable German-language information.

More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to » info@iqwig.de.

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