A new treatment algorithm for systemic immunoglobulin amyloid light-chain amyloidosis would see nearly a fifth of patients switched to second-line therapy after one month of first-line treatment.

The algorithm is based on study findings showing that patients with a baseline dFLC (difference in involved amyloidogenic and uninvolved serum free light chains) of more than 400mg/l and no haematological response one month after treatment initiation are extremely unlikely to improve their response.

It was developed by a research team at the UK’s National Amyloidosis Centre based at UCL, who analysed data on 525 patients with amyloidosis who had received front-line bortezomib between February 2010 and August 2019 and had less than a VGPR (very good partial response) at one month.

The data, published in The British Journal of Haematology, showed that after 6 months just 40% of patients improved response to ≥VGPR while 60% had not.

Also, 60% of patients who improved response to ≥VGPR at 6 months had achieved at least a partial response at 1 month, compared to just over half (33%) in those with <VGPR at 6 months.

The researchers then sought to identify the factors that would predict no response to treatment.

They found that patients with a baseline dFLC of >400mg/l (odds ratio [OR] 4.1), and no haematological response at 1 month (OR 4.8) were “extremely unlikely to improve their response”, and as such could benefit from being switched to a second-line regimen.

They also concluded that patients who achieve at least a partial response at one month and improve ≥VGPR by 3 months “mostly do not require a change in treatment as long as there is organ improvement”.

And as is generally current practice, any patient not achieving at least a VGPR by 3 months should be switched to a second-line regimen, they said.

Using their treatment algorithm, the researchers estimated that “nearly 19% of the patients would be recommended for treatment modification at one month, [and] 61% would be monitored for another 2 months and considered for modification of therapy if the response did not deepen”.

The study data “provides clinicians with clear and objective criteria to aid decisions about switching treatments in poor responders,” the researchers said.

But they also stressed that the data needs validation, “both in other large retrospective cohorts and prospective trials”, given the availability of newer treatment and the limitations of their study, such as its inability to model the impact of organ damage and also the lack of cytogenetic data from the bone marrow at diagnosis.