The CASTOR trial investigated the addition of the monoclonal anti-CD38 antibody, daratumumab, to one of the standard of care regimens, in this case bortezomib in combination with dexamethasone in patients with relapsed and refractory multiple myeloma after at least one prior treatment line. Those patients were equally randomised between daratumumab in combination with bortezomib and dexamethasone which was compared to bortezomib/dexamethasone alone. The bortezomib based treatment was terminated after eight cycles and the patients in the daratumumab arm continued with single agent daratumumab maintenance until disease progression and unacceptable toxicity. The primary endpoint of the trial was progression free survival and all patients had a pre-specified analysis also for minimal residual disease in case of suspected CR.

We have now done an updated analysis after an extended median follow-up of 19.4 months and here you see that the combination of daratumumab with bortezomib/dexamethasone had a median progression free survival of 16.7 months and this is compared to 7.1 months in the standard arm with a hazard ratio of 0.31. This advantage is highly significant. The patient group who benefitted most were those patients with only one prior treatment line; here the median PFS for daratumumab combination is not reached, still not reached, compared to 7.9 months in the standard arm. The patients who benefitted most were the patients when the daratumumab combination was used in early relapses.

Is there anything holding it back from being brought forwards as standard of care for these patients?

Fortunately the combination of daratumumab with bortezomib and dexamethasone was approved by the EMA in May, so one month ago. So it can be used as one of the new standards of care for relapsed multiple myeloma. We have many options for those patients; we can decide individually what is the best regimen for each individual patient considering age, comorbidities, prior treatments, potential toxicities. But it is now one of the newly approved standard of care regimens.