Background: The immunomodulatory agent pomalidomide is active in patients with relapsed/refractory multiple myeloma, including those who failed prior lenalidomide and bortezomib. Phase II clinical trials showed that pomalidomide is also effective in previously treated AL amyloidosis. The combination of pomalidomide and dexamethasone (PDex) showed a good hematologic response rate (more than partial response from 48 to 68%). Aim of this study is to report the efficacy of PDex in a retrospective real-world series of patients with AL amyloidosis from three European referral centers.

Methods: The databases of the Pavia Amyloid Research and Treatment Center (Italy), the Heidelberg Amyloidosis Center (Germany) and the National Amyloidosis Center of London (United Kingdom) were searched for patients with a diagnosis of AL amyloidosis treated with pomalidomide and dexamethasone (PDex). The patients received 28-day cycles of pomalidomide (from day 1 to 21) and dexamethasone (once weekly). All patients gave written informed consent for their clinical data to be used for research purposes. Hematologic and organ responses were assessed according to the International Society of Amyloidosis criteria.

Results: One hundred and fifty patients were included, 91 treated in Pavia, 30 in Heidelberg and 29 in London. Median age at the time of PDex initiation was 65 years (range: 34-85 years) and 92 (61%) patients were males. The heart was involved in 92 (61%) patients, the kidney in 87 (58%) and 91 (60%) of patients had two or more organs involved. The median NT-proBNP concentration at the time of PDex initiation was 1.670 ng/L (interquartile range, IQR: 527-4.963 ng/L) and 23 (15%) had NT-proBNP >8.500 ng/L. The estimated glomerular filtration rate was <30 mL/min per 1.73 m2 in 13 (9%) of patients and 16 (11%) were on dialysis at the time of PDex initiation. Median bone marrow plasma cells infiltrate at diagnosis was 18% (IQR: 10-30%) and this was ≥10% in 114 (76%) subjects. The median difference between involved and uninvolved concentration of free light chains (dFLC) was 150 mg/L (IQR: 76-397 mg/L). Median time from AL amyloidosis diagnosis to PDex treatment initiation was 11 months (IQR: 5-24 months). The median number of previous lines of therapy was 3 (range: 2-7) with 98 (65%) patients refractory to previous lines. One hundred and thirty-eight (92%) patients had previously received bortezomib, 120 (80%) lenalidomide and 114 (76%) melphalan and 39 (26%) underwent autologous stem cell transplant. The median number of PDex cycles performed was 3 (range: 1-30). Pomalidomide dosage was 4 mg in 56% of patients, 2 mg in 27%, 3 mg in 14% and 1 mg in 3% of subjects. Adverse events observed in 42 (28%) of subjects. With the limit of the retrospective setting, the more frequently reported were infections in 13 (31%), cardiac heart failure in 11 (26%), creatinine increase in 7 (16%) and cytopenia 4 (9%). The hematologic response rate at the end of cycle 3 was 36%, with 14 (16%) very good partial responses (VGPR) and 20 (20%) partial responses (PR). After cycle 6, the overall hematologic response rate was 56%, with 15 (26%) VGPR and 17 (30%) PR. A hematologic response to therapy was noted in 16 out of 39 subjects who were previously refractory to bortezomib, lenalidomide and melphalan. Median follow-up of living patients was 12 months (IQR: 7-27 months) and 64 (42%) patients died. Obtaining at least partial response at the end of cycle 3 was associated with a significant survival advantage (median survival not reached vs. 25 months, P=0.007, Figure). Cardiac responses were observed in 7 of 74 patients with measurable NT-proBNP (10%), but this can be underestimated due to the pomalidomide-related increase of NT-proBNP, and renal response in 13 of the 56 evaluable patients (23%).

Conclusions: The combination of pomalidomide and dexamethasone is active, with a 56% of response rate at cycle 6, in heavily pretreated patients with AL amyloidosis. The hematologic response rate of this real word retrospective study compares with those reported in phase 2 clinical trials, improved over time and patients who obtained a quick reduction of the burden of free light chains, had a significant survival benefit. Pomalidomide is an effective rescue agent for relapsed refractory AL amyloidosis.


Merlini:Akcea: Consultancy; Janssen: Consultancy; Ionis: Consultancy; Millenium: Consultancy; Prothena: Consultancy; Pfizer: Consultancy. Wechalekar:Janssen: Honoraria. Palladini:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel support; Prothena: Honoraria.

Author notes


Asterisk with author names denotes non-ASH members.