31st July 2020

Bortezomib-based induction with an alkylator (either cyclo or melphalan; VCD or VMD) has been extensively evaluated and demonstrated as beneficial in several large RCTs.[1,2]
VRD has not been assessed in any prospective clinical trials in systemic AL amyloidosis. The only report of VRD in AL amyloidosis is a retrospective case series in 34 patients reported in October 2019 by Kastritis et al in Blood Advances.[3] While response rates were promising (CR 32%), patients could only tolerate a dose of lenalidomide of 5 mg, and the authors concluded that VRD is associated with significant toxicity.
Supporting these concerns, bortezomib, pomalidomide, and dexamethasone (VPD) was assessed in a prospective trial in AL amyloidosis, but this was closed early due to toxicity.[4] The IMiDs as a class are less well tolerated in AL amyloidosis than in myeloma.
Thus, it is the recommendation of the Australian Amyloidosis Network that until further prospective clinical studies are undertaken, VCD should still be considered the standard of care as frontline treatment in systemic AL amyloidosis. Future optimisation of this backbone is likely to be with the addition of an anti-CD38 mAb rather than with an IMiD.[3]

Dr Simon Gibbs
A/Professor Peter Mollee
Dr Fiona Kwok
Dr Hasib Sidiqi

References
1. Kastritis E, Leleu X, Arnulf B et al, Bortezomib, melphalan and dexamethasone for light chain amyloidosis. J Clin Oncol. In press
2. Kastritis E, Palladini G, Minnema MC et al, Subcutaneous daratumumab and cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed light chain (AL) amyloidosis: primary results from the Phase 3 Andromeda Study. EHA 2020. LB2604.
3. Kastritis E, Gavriatopoulou, Roussou M, et al. Primary treatment of light-chain amyloidosis with bortezomib, lenalidomide, and dexamethasone.
Blood Adv. 2019 Oct 22; 3(20): 3002–3009
4. Zonder, JA, Sanchorawal V, Kukreti V, et al. Phase I Trial of Pomalidomide, Bortezomib, and Dexamethasone as Frontline Treatment of AL Amuloidosis. Blood (2017) 130 (Supplement 1): 3158.