Abstract

Background: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder. Lenalidomide, especially in conjunction with dexamethasone, has been shown to be highly active in patients with multiple myeloma. We previously reported a hematologic response rate of 41% and an organ response rate of 23% among 22 AL patients treated with lenalidomide and on-demand dexamethasone (Dispenzieri et al, Blood 2007). Long term outcomes of AL patients treated with lenalidomide have not yet been described.

Methods: Thirty-seven patients were treated on an IRB approved treatment trial with single agent lenalidomide, starting doses of 25 mg in 22 and reduced dose of 15 mg in the last 15. If progression within or no evidence of hematologic response after 3 cycles, dexamethasone was added. Patients were classified according to cardiac biomarker stage (cut-offs for serum troponin T <0.035 ng/ml and NT-proBNP <332 pg/ml--Stage I neither above cutoff; Stage III, both above cut-off; and Stage II, any one above cut-off). Survival estimates were done according to the methods of Kaplan and Meier.

Results: Median age was 64 years (range 44–88), with 70% male. Sixty-five percent of patients were previously treated, and the median time from diagnosis to study entry was 8.9 months (range 0.4–237). The biomarker staging breakdown was: I, 16%; II, 43%; and III, 41%. As of 7/11/08, 5 patients remain on active therapy. The overall hematologic response rate was 43% (1 CR and 15 PR), with only one patient responding to single agent lenalidomide, and the overall organ response rate was 20%. If one excludes the 13 patients who did not complete 3 months of therapy and have the opportunity of having dexamethasone added to their program, the respective hematologic and organ response rates were 62% and 32%. With a median follow-up of 33.6 months (range 14.4–42), twenty-two patients (59%) have died, but only 2 had deaths possibly related to treatment. Median duration of response, progression free survival and overall survival were 31 months, 14.8 months (95%CI: 5.7–28.1), and 18.8 months (95%CI: 11.7-not reached), respectively. Overall survival from diagnosis was 48 months (95%CI: 21.6–153.6). As shown in Table below, outcomes were dependent on underlying risk stratification and ability to stay on therapy. High risk patients were more likely to drop out early and less likely to respond. High risk patients had shorter OS

All Patients 
Outcome Stage I Stage II Stage III p 
16 15  
Survival from enrollment, mo NR 18.8 (11.7–33.6) 5.7 (3.2–18.3) 0.01 
Survival from Diagnosis, mo NR 48.4 (20.4–62) 21.1 (11.2–31.7) 0.005 
Progression Free Survival, mo 34.7 (33.7–NR) 18.3 (6.2–28.1) 4.4 (3–8.6) NS 
Drop out by cycle 4, % 17 31 60 NS 
Median # of cycles administered 31 0.04 
Time to response, mo 6.2 (3.6–9.3) 6.4 (5.2–NR) 4.7 (3.8–NR) NS 
Hematologic response rate, % 83 38 27 0.05 
Organ response rate, % 40 20 13 NS 
Duration of Response, mo NR 27.2 (13.6–NR) NR NS 
Subgroup analysis of patients receiving >3 cycles of therapy (i.e getting LenandDex) 
12  
Time on therapy, mo 35.2 10.5  
Hematologic Response Rate, % 100 50 56  
Organ response rate, % 50 27 25  
All Patients 
Outcome Stage I Stage II Stage III p 
16 15  
Survival from enrollment, mo NR 18.8 (11.7–33.6) 5.7 (3.2–18.3) 0.01 
Survival from Diagnosis, mo NR 48.4 (20.4–62) 21.1 (11.2–31.7) 0.005 
Progression Free Survival, mo 34.7 (33.7–NR) 18.3 (6.2–28.1) 4.4 (3–8.6) NS 
Drop out by cycle 4, % 17 31 60 NS 
Median # of cycles administered 31 0.04 
Time to response, mo 6.2 (3.6–9.3) 6.4 (5.2–NR) 4.7 (3.8–NR) NS 
Hematologic response rate, % 83 38 27 0.05 
Organ response rate, % 40 20 13 NS 
Duration of Response, mo NR 27.2 (13.6–NR) NR NS 
Subgroup analysis of patients receiving >3 cycles of therapy (i.e getting LenandDex) 
12  
Time on therapy, mo 35.2 10.5  
Hematologic Response Rate, % 100 50 56  
Organ response rate, % 50 27 25  

Conclusions: Based on these data, single agent lenalidomide is not recommended for patients with AL; however, lenalidomide in combination with dexamethasone can be associated with good progression free and overall survival rates, even among patients with relapsed or refractory disease.

Disclosures: Dispenzieri:Celgene: Research Funding. Lacy:Celgene: Research Funding. Kumar:Celgene: Research Funding. Greipp:Celgene: Speakers Bureau. Witzig:Celgene: Research Funding. Off Label Use: Lenalidomide in patients with amyloidosis.

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