This is a study that evaluated the addition of daratumumab, subcutaneous daratumumab, to the standard therapy for AL amyloidosis which is a combination of bortezomib with cyclophosphamide and dexamethasone. This was a prospective randomised study which enrolled patients with newly diagnosed light chain amyloidosis.
What were your methods?
This was a prospective randomised study, there was no placebo control but it was an active control study. The patients that received subcutaneous daratumumab with CyBorD, they received this therapy for six months and then they received maintenance with daratumumab monotherapy, with subcutaneous daratumumab, for a maximum of 24 months. The other group, the control group, received therapy with standard CyBorD for six months which is the standard of care across different countries in the world.
What did you find?
The most impressive finding of this study was the significant increase in terms of complete haematological responses in patients that received a combination of daratumumab with CyBorD over CyBorD alone. There were 53% complete haematological responses in the daratumumab arm versus 18% in the standard of care arm.
This was also associated with a significant increase in time to major organ deterioration and to death or haematologic progression. This very high haematologic response, complete haematologic response, was also translated into a doubling of organ responses at six months.
What are you concluding from these results?
Based on the results of the ANDROMEDA study we can say that the addition of subcutaneous daratumumab to standard CyBorD therapy substantially improves complete haematologic response rates. This is translated to an increase in the time to major organ deterioration, disease progression, haematologic relapse or death and also in almost doubling the rates of organ responses. This means that this is a very effective study.
This was also associated with a very predictable and mild toxicity. There were no significant signals of additional toxicity beyond what is already known. Also this will probably become the new standard of care for patients with light chain AL amyloidosis across the world. As far as I know, the company will submit for approval of this combination in different countries across the globe.
A practice changing study – these results are practice changing. It is one of the few studies, randomised studies, in this field which is a rare disease. It is very reassuring, the fact that we see so high complete haematologic response rates and with manageable toxicity.