1. Reeder CB et al. ASCO 2009; Abstract 8569. (Poster)
Efficacy and Safety of Lenalidomide (R) Oral Monotherapy in Patients with Relapsed or Refractory Mantle Cell Lymphoma (MCL): Results From an International Study (NHL-003)
Reeder CB et al.
ASCO 2009; Abstract (Poster)

2. Introduction
Lenalidomide (R), an immunomodulatory agent, can enhance T-cell and natural-killer-cell activation leading to an improvement in tumor-cell/T-cell synapse formation in B-cell cancers and an enhancement in immune-mediated MCL cell kill
R also exerts antiproliferative activity in MCL via enhanced tumor suppressor gene expression (including p21 and SPARC), G1 cell cycle arrest, caspase activation and apoptosis
NHL-002: R in relapsed or refractory MCL: ORR = 53%, DoR = 13.7 mos
Current study objectives:
Interim subset analysis of patients with MCL (n = 54) evaluable for response in NHL-003 (N = 218 patients with aggressive forms of NHL)
Evaluate the ORR, DoR, PFS and safety of single-agent R (25 mg/daily d1-21 q28 days) in patients with MCL who had relapsed or were refractory to at least 1 prior treatment regimen
Source: Reeder CB et al. ASCO 2009; Abstract 8569.

3. Mechanism of Action of Lenalidomide in NHL
E2F
G1 arrest
CDK4/6 Rb
Cyclin D
p21
CDK2 P
Cyclin E Rb
Cell cycle progression
E2F
In NHL, R enhances tumor suppressor genes (including p21) leading to reduced
cyclin-dependent kinase (CDK) activity and reduced phosphorylation of pRb,
which results in cellular growth arrest in the G0/G1 phases of the cell cycle.
Source: Reeder CB et al. ASCO 2009; Abstract 8569.

4. Patient Characteristics and Objective Response
Median time from diagnosis (range)
3.2 yrs ( )
Presence of > 1 extranodal site
28%
International Prognostic Index score
0-2
3-5
53.7%
46.3%
Prior therapies
Median no. of prior therapies (range)
Refractory to last chemotherapy
Prior stem cell transplant
Prior bortezomib treatment
3 (1-8)
33.3%
25.9%
32.0% N
ORR
CR/CRu PR
MCL, all patients 54
43%
17%
26%
MCL-bortezomib treated 17
53%
18%
35%
MCL-stem cell treated 14
57%
14%
Source: Reeder CB et al. ASCO 2009; Abstract 8569.

5. Most Common Grade 3 and 4 Adverse Events (N = 54)
Hematologic AEs
Neutropenia
22.2%
20.4%
Febrile neutropenia
1.9%
3.7%
Thrombocytopenia
11.1%
Anemia
9.3%
Leukopenia
5.6%
Nonhematologic AEs
Fatigue 0%
Dyspnea
Abdominal pain
Asthenia
Acute bronchitis
Source: Reeder CB et al. ASCO 2009; Abstract 8569.

6. Summary and Conclusions
Overall, patients with relapsed or refractory, heavily pretreated MCL achieved an ORR = 43%, CR = 17% to single-agent R
ORR = 57%, CR = 14% in prior stem cell transplant-treated
ORR = 53%, CR = 18% in prior bortezomib-treated
Median PFS = 6.2 months and DoR has not yet been reached
Most common Grade 3/4 AEs: neutropenia (43%), thrombocytopenia (22%) and anemia (11%)
13% of patients discontinued R due to AEs
28% of patients had dose reductions due to AEs
R is a promising treatment option for patients with MCL
Clinical trials with R alone or combined with chemotherapy are ongoing in MCL
Source: Reeder CB et al. ASCO 2009; Abstract 8569.