Is There a Role for Thalidomide Maintenance in the Treatment of AL Amyloidosis?.
Authors: Gibbs Simon DJ , Sattianayagam Prayman T , Gillmore Julian D , Offer Mark , Lachmann Helen J , Hawkins Philip N , Wechalekar Ashutosh D 
Published: October 2019

Abstract
Abstract 1863
Poster Board I-888
The role of thalidomide maintenance has been the subject of much debate in the setting of multiple myeloma, however its use in AL amyloidosis has not been previously reported. We report our experience with thalidomide maintenance in patients who had previously received risk adapted cyclophosphamide, thalidomide and dexamethasone chemotherapy (CTD) for the treatment of AL amyloidosis, specifically examining its relationship to clonal response, time to clonal progression, overall survival and toxicity.
All patients who achieved either a partial (PR) or complete response (CR) to CTD between 2002 – 2008 were identified from the database of the UK National Amyloidosis Centre, London and included in this study. Clonal and organ involvement and responses were assessed according to international consensus criteria for AL amyloidosis (Gertz et al, 2005). Progression-free (PFS) and overall survival (OS) was assessed by the method of Kaplan-Meier (KM) both for patients who did and did not receive thalidomide maintenance after a clonal response to CTD. PFS was defined as time to clonal progression after commencement of CTD. Thalidomide maintenance was defined as ongoing treatment with single agent thalidomide after CTD.
The total number of patients achieving a clonal response to CTD was 108. Thalidomide maintenance was administered to 25 patients (23%), including 6 patients (24%) with symptomatic myeloma. Of these 25 patients, males accounted for 40%. The median age was 60 years (range 42–77). Median number of organs with AL amyloidosis involved was 2. Before thalidomide maintenance, 11 patients had achieved a CR with CTD (44%) and 14 had achieved a PR (56%). The median number of cycles of CTD administered before thalidomide maintenance was 4.5 (range 1 – 7).
The median dose of thalidomide administered as maintenance treatment was 50mg daily (range 50mg alternate days to 200mg daily). The median length of maintenance was 10 months (range 1–70 months). Toxicity was the most common reason for cessation of maintenance treatment. After thalidomide maintenance, only 2/14 patients had an improvement in clonal response (14%). One patient had converted a near complete remission (nCR) to CR and another had converted a serum free light chain (FLC) PR to an FLC CR, but without a whole paraprotein response. Clonal progression was seen in 3/25 (12%) patients during thalidomide maintenance treatment, with another 7 patients relapsing after thalidomide was ceased (10 patients (40%) in total). Organ responses were seen in 3 patients - 2 cardiac and one liver - however these patients were already in a clonal CR after CTD treatment before thalidomide maintenance. 19 patients had stable organ involvement with AL amyloidosis. Organ disease progression was seen in 3 patients. Grade 2 or greater toxicity was reported in 18/25 patients (72%) with neuropathy the most common symptom, reported in 10/25 (40%) patients. All but one patient experienced new onset neuropathy after 10 months of thalidomide maintenance.
The median follow-up of the thalidomide maintenance patients was 27 months (range 8–71 months). The median KM estimated OS was not reached for patients who either received CTD alone or with thalidomide maintenance. The median PFS was 33 months for patients treated with CTD alone, whereas this had not yet been reached for those treated with thalidomide maintenance (log rank p = 0.55).
In conclusion, thalidomide maintenance after CTD in AL amyloidosis is associated with a high rate of additional toxicity (72%) with only minor improvements in clonal responses (14%) and no improvement in overall survival. There is a suggestion that thalidomide maintenance may delay clonal progression however. The optimal dose for thalidomide maintenance is unknown. While this study is small, we suggest that thalidomide should not be routinely used as maintenance therapy in AL amyloidosis. In selected patients who achieve a good clonal response to CTD and tolerate this chemotherapy well, there may be an argument for thalidomide maintenance if a prolongation in PFS is desired. Agents with less toxicity such as lenalidomide might be preferable and need to be further examined in the maintenance setting.
Patients with CTD only Patients with CTD and thalidomide maintenance Number patients 83 25 Males 63% 40% CR at end of CTD 41% 44% Median PFS 33 months Not yet reached Further clonal response with thal maintenance NA 14% Grade 2 + toxicity with thal maintenance NA 72%

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