Abstract

Abstract 2901

Poster Board II-877

Thalidomide and lenalidomide are two immunomodulatory agents that engender an intriguing treatment activity in a subset of pts with MF that includes a clinically relevant benefit in terms of both anemia and splenomegaly. Using the International Working Group (IWG) consensus criteria, we assessed the efficacy and longterm outcome of these two agents in three consecutive studies run at MD Anderson Cancer Center between February 2000 and March 2007 in pts with MF. One hundred and six pts were treated in three phase II trials. Twenty-five pts received single-agent thalidomide; 41 pts received single-agent lenalidomide; and 40 pts were treated with a combination of lenalidomide and prednisone. Patients' characteristics are summarized in Table 1. There was no significant difference between the 3 study groups except for a higher percentage of splenomegaly (p=0.012) and a performance status 1 (p=0.017) observed in pts treated with the combination of lenalidomide-prednisone. In addition, pts receiving lenalidomide therapy had received more previous therapies. After a median follow-up of 15 months (range, 2 to 112 months), 7 the 25 pts (28%) treated with thalidomide responded with complete response (CR) observed in 1 pt (4%), partial response (PR) in 1 pt (4%) and clinical improvement (CI) in 5 pts (20%). The median duration of response was 7 months (range, 3 to 40 months). Of the 41 pts treated with single-agent lenalidomide, 14 (34%) responded with 3 (7%) CR, 4 (10%) PR, and 7 (17%) CI. The median follow-up and median duration of response were 20 months (range, 2 to 55 months) and 16 months (range, 6 to 44 months), respectively. After a median follow-up of 8 months (range, 4 to 37 months), 15 of the 40 pts (38%) treated with the combination of prednisone and lenalidomide responded: 2 (5%) CR, 2 (5%) PR, and 11 (28%) CI. The median duration of response was 14+ months (range, 4 to 30+ months). One of the pts treated with a combination of lenalidomide-prednisone converted his response from PR to CR recently. There was a trend for faster responses in pts treated with combination versus single agent-lenalidomide: the median time to response was 60 and 80 days respectively (p=0.06). We then compared the efficacy of these three regimens. There was a trend for a higher efficacy in pts receiving the lenalidomide-prednisone combination (Table 2). In conclusion, immunomodulatory agents such as thalidomide and lenalidomide are effective in the treatment of pts with MF. The combination of lenalidomide and prednisone appears to be more effective and can induce faster responses.

Table 1.
Patients' Characteristics Lenalidomide
 
Lenalidomide-Prednisone
 
Thalidomide
 
p-value  
N= 41 N=40 N=25  
Age, median (yrs) 64 (42-83) 64(42-86) 66 (40-85) 0.862 
No. of prior treatments (range) 2 (1-7) 2(1-5) 1 (1-3) 0.000 
Hemoglobin (gm/dL, range) 9.8 (6.9-14.8) 9.8(6.6-15.4) 9.3 (6.6-12.6) 0.092 
Platelet (x 109/L, range) 203 (34-901) 237(8-1005) 130 (20-391) 0.111 
WBC Count (x 109/L, range) 9 (2.4-45.4) 8.6(1.1-28.3) 7.3 (2-59.5) 0.507 
%Neutrophils (range) 66 (32-89) 66(10-89) 64 (30-90) 0.825 
Splenomegaly     
Yes (%) 20 (49) 31 (78) 14 (56) 0.012 
No (%) 14 (34) 9 (22) 10 (40)  
Splenectomy (%) 7 (17) 0 (0) 1 (4)  
Spleen Size (cm, range) 12 (3-30) 11.5 (1-25) 12.5 (3-25) 0.54 
Cytogenetics (%) Diploid 25 (61) 21 (52) 15 (60) 0.651 
Non-Diploid 15 (37) 19 (48) 9 (36)  
 Not available 1 (2) 0 (0) 1 (4) 
Myelofibrosis (%)     
Primary 29 (71) 31 (78) 18 (72) 0.96 
Post ET 7 (17) 5 (12) 5 (20) 0.77 
Post PV 5 (12) 4 (10) 2 (8) 0.24 
Performance Status (%)     
16 (39) 4 (10) 5 (20) 0.017 
22 (54) 32 (80) 15 (60)  
3 (7) 4 (10) 5 (20) 
Patients' Characteristics Lenalidomide
 
Lenalidomide-Prednisone
 
Thalidomide
 
p-value  
N= 41 N=40 N=25  
Age, median (yrs) 64 (42-83) 64(42-86) 66 (40-85) 0.862 
No. of prior treatments (range) 2 (1-7) 2(1-5) 1 (1-3) 0.000 
Hemoglobin (gm/dL, range) 9.8 (6.9-14.8) 9.8(6.6-15.4) 9.3 (6.6-12.6) 0.092 
Platelet (x 109/L, range) 203 (34-901) 237(8-1005) 130 (20-391) 0.111 
WBC Count (x 109/L, range) 9 (2.4-45.4) 8.6(1.1-28.3) 7.3 (2-59.5) 0.507 
%Neutrophils (range) 66 (32-89) 66(10-89) 64 (30-90) 0.825 
Splenomegaly     
Yes (%) 20 (49) 31 (78) 14 (56) 0.012 
No (%) 14 (34) 9 (22) 10 (40)  
Splenectomy (%) 7 (17) 0 (0) 1 (4)  
Spleen Size (cm, range) 12 (3-30) 11.5 (1-25) 12.5 (3-25) 0.54 
Cytogenetics (%) Diploid 25 (61) 21 (52) 15 (60) 0.651 
Non-Diploid 15 (37) 19 (48) 9 (36)  
 Not available 1 (2) 0 (0) 1 (4) 
Myelofibrosis (%)     
Primary 29 (71) 31 (78) 18 (72) 0.96 
Post ET 7 (17) 5 (12) 5 (20) 0.77 
Post PV 5 (12) 4 (10) 2 (8) 0.24 
Performance Status (%)     
16 (39) 4 (10) 5 (20) 0.017 
22 (54) 32 (80) 15 (60)  
3 (7) 4 (10) 5 (20) 
Table 2.
Parameter Lenalidomide N=41 Lenalidomide-Prednisone N=40 Thalidomide N=25 P-value  
Response (%)     
Overall 14 (34) 15 (38) 7 (28) 0.66 
CR 3 (7) 2 (5) 1 (4)  
PR 4 (10) 2 (5) 1 (4)  
CI 7 (17) 11 (28) 5 (20)  
Median Follow-up (mo, range) 20 (2-55) 8 (4-37) 67 (2-112)  
Median Response (mo, range) 16 (6-44) 14+ (4-30) 7 (3-40) 0.37 
Parameter Lenalidomide N=41 Lenalidomide-Prednisone N=40 Thalidomide N=25 P-value  
Response (%)     
Overall 14 (34) 15 (38) 7 (28) 0.66 
CR 3 (7) 2 (5) 1 (4)  
PR 4 (10) 2 (5) 1 (4)  
CI 7 (17) 11 (28) 5 (20)  
Median Follow-up (mo, range) 20 (2-55) 8 (4-37) 67 (2-112)  
Median Response (mo, range) 16 (6-44) 14+ (4-30) 7 (3-40) 0.37 

Disclosures:

Jabbour:Novartis: Speakers Bureau; Bristol Myers Squibb : Speakers Bureau.

Author notes

*

Asterisk with author names denotes non-ASH members.