Real world outcomes of pomalidomide for treatment of relapsed light chain amyloidosis

Abstract

Pomalidomide is a next-generation immunomodulatory agent with activity in relapsed light chain (AL) amyloidosis, but real world outcomes are lacking. We report the experience of the UK National Amyloidosis Centre. All patients with AL amyloidosis treated with pomalidomide between 2009 and 2017 were included. Data was collected on treatment toxicity and clonal response. Survival was calculated by the Kaplan-Meier method and outcomes reported on an intent-to-treat (ITT) basis. A total of 29 patients treated with pomalidomide were identified. Haematological responses at 3 months were: complete response (CR) nil, very good partial response (VGPR) 10 (35%), partial response (PR) 9 (31%), stable or progressive disease 7 (24%), unevaluable 3 (10%). On an ITT basis (n = 28), responses at 6 months were: CR- nil, VGPR-11 (39%), PR-2 (7%) and the remaining patients were non-responders 15 (53%). Median overall survival was 27 months (95% confidence interval 15·7-38·1 months). Median progression free survival (PFS) was 15 months (95% confidence interval 6·24-23·77). In conclusion, pomalidomide has activity in patients with relapsed AL amyloidosis. Responses are rapid and early responses may be predictive of a sustained overall response. Deep responses (VGPR or better) are seen in only a third of all patients and combination therapy needs to be explored.

Rapid response to single agent daratumumab is associated with improved progression-free survival in relapsed/refractory AL amyloidosis

“…Importantly, the majority of patients included in this study had already been treated with both bortezomib (92.5%) and lenalidomide (83.0%) therapyboth common agents used in the upfront setting. These response rates appear to be superior to those achieved with alternate novel agents in the relapse setting such as ixazomib (53% [10]), pomalidomide (46-61% [11]) and carfilzomib (63% [12]). Furthermore, the toxicity profile is manageable with grade III AEs seen in just 11.3%, which compares favourably with alternative agents [ixazomib: 59% [10], carfilzomib: 71% [12]].…”

Systemic amyloidosis: moving into the spotlight

“…Pomalidomide is rapidly acting (responses in approximately 1 month) and has shown a survival advantage as salvage therapy in heavily pre-treated patients [61][62][63] . A recent report demonstrated 66% haematological response with a median PFS of 15 months although no patients achieved a CR with pomalidomide alone 64 . Further evaluation of pomalidomide as part of combination chemotherapy is required to assess its efficacy in this setting although toxicity may be an issue in heavily pre-treated patients with our study reporting a 41.1% (7/19 evaluable patients) discontinuation rate due to adverse events in patients with a median of 4 prior lines of therapy.…”

Conventional Therapy for Amyloid Light-Chain Amyloidosis

“…Of note, the maximum tolerated daily dose of lenalidomide for AL amyloidosis patients is 15 mg, which is lower than that commonly used in multiple myeloma. Based on the encouraging results with lenalidomide, pomalidomide only (or in combination with dexamethasone) was also used to rescue patients with AL amyloidosis [46-49]. In these studies, the overall hematologic response rate ranged from 44 to 68%, with CR in 0–30% of cases.…”