In AL Amyloidosis, Both Oral Melphalan and Dexamethasone (Mel-Dex) and Risk-Adapted Cyclophosphamide, Thalidomide and Dexamethasone (CTD) Have Similar Efficacy as Upfront Treatment.
Authors: Gibbs Simon DJ , Gillmore Julian D , Sattianayagam Prayman T , Offer Mark , Lachmann Helen J , Hawkins Philip N , Wechalekar Ashutosh D 
Published: October 2019

Abstract
Abstract 745
The treatment of AL amyloidosis has evolved rapidly over the last few years. The role of autologous stem cell transplantation is controversial and oral combination chemotherapy is often the treatment of first choice. The optimal induction regime is not uniformly agreed upon although some consider oral Mel-Dex as the current “standard of care”. We report our large experience with both Mel-Dex and CTD as upfront treatment for AL amyloidosis in a comparative retrospective study and compare these findings with those of our smaller prospective randomized trial (UKATT), also to be presented as this meeting, using the same treatment regimens (Gillmore et al).
Patients treated with Mel-Dex and CTD as first-line treatment between 2002–2009 were identified from the database of the UK National Amyloidosis Centre, London. Organ involvement and responses were assessed according to international consensus criteria (Gertz et al, 2005).
The results are summarised below. Our CTD experience has previously been reported at this Congress (Gibbs et al, 2008). A total of 58 patients received Mel-Dex and 122 patients received CTD as upfront therapy. The baseline characteristics of the two groups were not significantly different in terms of median number of organs involved (by both consensus criteria and 123I labelled serum amyloid P component (SAP) scintigraphy), cardiac involvement, creatinine clearances (CrCl) <30ml/min, and NT-ProBNP levels. The Mel-Dex group was an older population, and there was a trend that their CrCl was lower at diagnosis.
The median number of cycles administered for both treatments was 5 (range 1–15). More patients presenting with neurological involvement were treated with Mel-Dex. The clonal response rates between the two regimens were not significantly different. The median time to best serum free light chain response (FLC) response for CTD was 2 months (range 1–5 months) versus 3 months for Mel-Dex (range 1–7). At 12 months, organ responses were observed in 44/113 (39%) patients treated with CTD compared to 12/56 (21%) patients treated with Mel-Dex (p = 0.03). Most Mel-Dex responses were renal.
The median follow-up is 19 months and the median time to clonal progression was not reached in either group. There was no significant difference in the estimated overall survival at 3 years.
Toxicity of any grade was reported by 76% of Mel-Dex patients and 84% of CTD patients (p=0.30). The commonest severe toxicity in both groups was fluid retention.
In conclusion, this is the largest comparative series of oral Mel-Dex and CTD in AL amyloidosis. Both regimes are not significantly different in terms of complete (CR) and overall response (OR) rates, toxicity, time to clonal progression or overall survival. There is a suggestion that time to best FLC responses with Mel-Dex is slower than CTD (3 vs 2 months). These results concur with the results of our prospective UKATT trial. Mel-Dex has the disadvantages of being a stem cell toxic regimen, requiring dose adjustment in renal failure. CTD is a reasonable alternative to Mel-Dex in the treatment of AL amyloidosis and a large international randomized prospective trial should be considered. Patient Characteristics at DiagnosisMel-DexCTDp-valueNumber of patients58122Median age (years)7264<0.0001 Males (%)7146Lambda FLC excess (%)7175Abnormal SAP scintigraphy (%)9185Median number organs involved22Median NT Pro-BNP (pmol/L)1241740.84 Median Creatinine (umol/L)9392Median CrCl (ml/min)59730.07 CrCl <30ml/min1415Organs Involved (% patients)Kidney8677Cardiac4748Nervous System3316Liver1018Gastrointestinal107Soft Tissue3119Treatment ResponsesFLC CR, n (%)14/45 (31%)36/96 (38%)FLC PR, n (%)20/45 (44%)40/96 (42%)Overall CR10/56 (18%)28/117 (24%)0.48 Overall PR28/56 (50%)46/117 (39%)Overall Response38/56 (68%)74/117 (63%)0.67 Organ responses12/56 (21%)44/113 (39%)0.03 Renal organ responses11/50 (22%)35/96 (36%)0.11 Median time to FLC PR (months)21Median time to best FLC response (months)32Toxicity, any grade44/58 (76%)102/122 (84%)0.30 Overall survival at 3 years44/57 (77%)90/122 (74%)NS

Disclosures:
Off Label Use: Off-label use of thalidomide.