Autologous Stem Cell Transplantation (ASCT) Versus Oral Melphalan and High-Dose Dexamethasone in Patients with AL (Primary) Amyloidosis: Results of the French Multicentric Randomized Trial (MAG and IFM Intergroup).
Authors: Jaccard A. , Moreau P. , Leblond V. , Leleu X. , Benboubker L. , Hermine O. , Recher C. , Malphette M. , Lioure B. , Royer B. , Grosbois B. , Jaubert J. , Preux P.M. , Cogne M. , Fermand J.P. 
Published: April 2020

A prospective randomized trial was conducted to compare in AL amyloidosis ASCT (melphalan 140 or 200 mg/m2 depending on age and clinical status supported with ASCT collected with G-CSF alone) and the oral regimen M-Dex (melphalan 10 mg/m2 and dexamethasone 40 mg for 4 days each months up to 18 months). The objectives were to compare survival and hematologic and clinical responses.

Between January 2000 and January 2005, 100 patients (pts) (56 males) below 70 years of age with biopsy proven systemic AL amyloidosis, no more than 2 prior courses of chemotherapy and an ECOG performans status &lt; 3 were randomized after informed consent, 50 in each arm, in 29 French centers. Organ involvement and treatment response were evaluated using the consensus opinion from the international Tours symposium on amyloidosis (Am J Med2005, 79:319–328).

Median age was 58 (40–69), median time from diagnosis to randomization was 48 days (8 – 1194), median number of organs involved was 2 (1 – 5), heart in 46 pts (23 in each arm), kidney in 64 pts (32 in each arm), liver in 29 pts and nerve in 10 pts. In the ASCT arm 37 pts (74%) received the planned treatment, 10 pts received melphalan 140 and 27 pts melphalan 200, 13 pts did not received ASCT, for disease progression in 12 with 10 deaths before day 51 after randomization (4 during G-CSF treatment). Early transplant related mortality (within 100 days) was 24% (9 pts). In the M-Dex arm 1 pt died during the first course of cardiac arrhythmia (2%). Pts who received 3 courses of M-Dex or more or survived more than 3 months after ASCT were evaluated for response. No statistically significant difference between the 2 arms was found for hematologic responses, with M-Dex 12 CR and 13 PR among 38 evaluable pts (65%), with ASCT 10 CR and 6 PR among 25 evaluable pts (64%) or clinical responses, with M-Dex organ responses in 18/44 evaluable pts (40%) and 15/29 with ASCT (52%). With a median follow-up of 13.3 months for the entire cohort and 29.3 months for living pts 44 pts have died, 25 in the ASCT arm and 19 in the M-Dex arm. The Kaplan-Meier estimated median survival is 56.9 months for the M-Dex arm and 48.6 months for the ASCT arm (p=0.2 by log-rank test). 60 pts met the Mayo clinic eligibility criteria for ASCT, survival in M-dex arm is slightly better for these pts (p=0.12) and curves are similar for the 40 more severe pts between the 2 arms (p=0.97). Two centers included 38 pts, there is no difference for total survival (p=0.71) between patients treated in these 2 centers or in the 27 other centers who have included a median of 2 pts (range 1–6) but if there is a slightly better survival for ASCT in these 2 centers (p=0.38) there is a significantly better survival for pts treated in the 27 centers in the M-Dex arm compared to ASCT arm (p&lt; 0.006).

In conclusion our study confirms the efficacy and tolerance of M-Dex in AL amyloidosis. ASCT is not superior to M-Dex in a multicentric setting and is associated with lower survival when pts are treated in centers without a great experience. In referral centers the superiority of ASCT compared to an efficient treatment like M-Dex remains to be proven.