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EHA 2025 | Daratumumab, bortezomib, thalidomide & dexamethasone in treatment-naive systemic AL amyloidosis
Jahanzaib Khwaja, MD, FRCPath, University College London Hospitals NHS Foundation Trust, London, UK, discusses the outcomes of daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTD) in a UK cohort of treatment-naive patients with systemic light chain (AL) amyloidosis. The results with the treatment regimen were encouraging, and Dr Khwaja suggests that the addition of immunomodulatory drugs to frontline treatment may benefit this patient population. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
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Transcript
We in the UK looked at daratumumab, bortezomib, thalidomide, dexamethasone, which is a quadruplet regimen that actually hasn’t really been looked at elsewhere in the world in systemic AL amyloidosis. And it’s a unique feature because for a period of time we had access to this in the UK. And traditionally immunomodulatory drugs have been thought to be very difficult in patients with AL amyloidosis because of their potential cardiac toxicities, potential fluid overload, arrhythmias, neuropathy, etc...
We in the UK looked at daratumumab, bortezomib, thalidomide, dexamethasone, which is a quadruplet regimen that actually hasn’t really been looked at elsewhere in the world in systemic AL amyloidosis. And it’s a unique feature because for a period of time we had access to this in the UK. And traditionally immunomodulatory drugs have been thought to be very difficult in patients with AL amyloidosis because of their potential cardiac toxicities, potential fluid overload, arrhythmias, neuropathy, etc. So they’ve been avoided particularly in the first-line setting traditionally and the big trials have looked at DARA-VCD with cyclophosphamide rather than an immunomodulatory drug.
We actually found that DARA-VTD in our patient cohort of over 100 patients in the UK did extremely well. And we did some dose modifications with the thalidomide. So we capped the dose at 50 milligrams. We introduced it slowly into the cycle. There were dose modifications along the way, but actually it appeared to be very well tolerated and outcomes were really excellent. Now, it’s difficult to compare this to a cohort with the DARA-VCD because it’s not a direct comparator group, but certainly they have excellent outcomes. And I think in the future, we will need to look at readdressing whether immunomodulatory drugs are something that could be considered in the first-line setting. And there is ongoing work at comparing DARAVC-D and DARA-VTD in these kind of historic cohorts. And that’s something which potentially would give us some really useful information.
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