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FDA approves first immunotherapy combo

US regulators approved Bristol-Myers Squibb's combination of nivolumab and ipilimumab for the treatment of metastatic melanoma, marking the first approval for an immunotherapy combination.

Both drugs are checkpoint inhibitors that remove the brakes from T cells. Ipilimumab, first approved in 2011 for the treatment of melanoma, blocks cytotoxic T lymphocyte antigen 4 (CTLA4) to enable activation of T cells in lymph nodes. Nivolumab, first approved in 2014, ties up the programmed cell death protein 1 (PD1) to prevent T cell inactivation by PD1 ligands, which are overexpressed in some types of cancers. Although both drugs provide compelling efficacy when used as monotherapies, oncologists have been awaiting immunotherapy combinations since the original approval of ipilimumab.

The new approval was supported by a 142-patient study in previously untreated patients with unresectable or metastatic melanoma. 61% of patients treated with the combination achieved the primary end point of an objective response rate, compared with 11% treated with ipilimumab alone (N. Engl. J. Med. 372, 2006–2017; 2015). 22% of combination-treated patients achieved a complete response, compared with no patients in the ipilimumab monotherapy arm. The trial has not yet reached a median progression-free survival for the combination arm, with a minimum of 11 months of follow up. Patients who received the combination therapy did report almost twofold as many grade 3 or 4 adverse events as did the patients who received ipilimumab monotherapy.

Despite excitement over this efficacy, oncologists have been raising concerns over the cost of immunotherapy drugs, especially as the field moves towards multidrug regimens. In the case of this first combination, in the United States, patients will receive four doses of ipilimumab plus nivolumab at a cost of around US$140,000, followed by nivolumab alone at a cost of over $12,000 per month, until the disease progresses.

With dozens of drugs in development against other immunotherapy targets, researchers are exploring lots of other combination options (Nat. Rev. Drug. Discov. 14, 561–584; 2015).


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Mullard, A. FDA approves first immunotherapy combo. Nat Rev Drug Discov 14, 739 (2015).

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