ASCO sees emerging crop of myeloma therapies

A string of new clinical trial results in multiple myeloma reported at ASCO suggest patients could soon have another line of treatment options if initial therapy starts to lose its benefits.

Multiple myeloma – a form of cancer affecting white blood cells – has benefited from a number of new drugs reaching the market in recent years, although as patients typically relapse there is still a pressing need for additional lines of therapy.

Johnson & Johnson (J&J) kicked off proceedings at ASCO with data from a phase II trial of its daratumumab candidate showing that the antibody was able to achieve a response rate of 30 per cent, even in patients who had been through up to five prior treatment regimens.

Daratumumab is an anti-D38 antibody that was awarded breakthrough status by the FDA in 2013 for relapsed myeloma.

In the 106-patient trial, daratumumab was able to extend survival by 3.7 months in this population who had been treated with a number of widely-used therapies including Celgene's Revlimid (lenalidomide) plus dexamethasone, Takeda's Velcade (bortezomib), Amgen's Kyprolis (carfilzomib) and Celgene's Pomalyst (pomalidomide).

After one year's treatment, two-thirds of the patients treated with J&J's drug were still alive, even though most of them would not be expected to live beyond six months, according to lead investigator Sagar Lonial of Emory University in the US.

J&J said it was hoping to press ahead with regulatory filings for daratumumab based on the phase II data in the US, with commentators noting that the response rate of around 29 per cent was similar to that seen in trials that led to the approval of Kyprolis.

Daratumumab – originally developed by Denmark's Genmab – is vying with two other CD38-targeting antibodies that are also in development as potential myeloma therapies, namely Sanofi's SAR650984 and MorphoSys' MOR202 which are in phase I and II testing, respectively.

MorphoSys also presented data on its candidate at ASCO, with the results of a phase I/II trial indicating the drug was safe and well-tolerated when delivered as a two-hour infusion and 'promising early signs of activity' including 'long-lasting tumour control ... in early cohorts', according to the company.

Also showing promise in myeloma was Bristol-Myers Squibb (BMS) and AbbVie's elotuzumab, an anti-Signalling Lymphocytic Activation Molecule F7 (SLAMF7) antibody that works by killing myeloma cells directly as well as targeting an immune response against the cancer.

The phase III ELOQUENT-2 trial reveals that giving the antibody alongside Revlimid and dexamethasone reduced the risk of disease progression or death by 30 per cent compared to Revlimid and dexamethasone alone, with the benefit extending for more than three years of follow-up.

The overall response rate for the elotuzumab regimen in the study was 79 per cent, compared to 66 per cent for the control group.

A 152-patient phase II trial looking at the efficacy and safety of elotuzumab plus Velcade and dexamethasone also reveals that patients treated with the combination achieved median progression-free survival of 9.7 months, compared to 6.9 months for Velcade and dexamethasone alone.

Elotuzumab has also been deemed a breakthrough therapy by the FDA for relapsed myeloma, and BMS and AbbVie are now on course to file for approval.

Analysts have suggested both daratumumab and elotuzumab have blockbuster sales potential with BMS/AbbVie's candidate on course for a possible launch later this year and J&J's drug expected to debut in 2016.