Pietronigro, Dennis

Abstract Background: Lenalidomide (Revlimid®) has been reported to show activity in non-Hodgkin’s Lymphoma (NHL). However, prognostic factors predicting an individual patient’s response were unavailable. Aim: To investigate prognostic factors for lenalidomide response in patients with relapsed/refractory aggressive NHL. Methods: Patients with relapsed/refractory aggressive NHL with measurable disease ≥2 cm after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1-21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Univariate analyses using Fisher’s exact test and multivariate analyses using logistic regression were conducted to investigate associations of prognostic variables with response. Results: Forty-nine patients received lenalidomide oral monotherapy. The median age was 65 (23-86) and 24 were female. Histology was diffuse large B-cell lymphoma (n=26), follicular center lymphoma grade 3 (n=5), mantle cell lymphoma (n=15) and transformed (n=3). Median time from diagnosis was 2.7 (0.4-32) years and median number of prior treatment regimens was 4 (1-8). Forty-five (92%) of the patients had received prior rituximab and 63% were rituximab-refractory. Seventeen patients (35%) exhibited an objective response (2 complete responses, 4 complete responses unconfirmed and 11 partial responses). Response to lenalidomide was the same for patients who were refractory to rituximab (30%) and those who were not (31%). Three of 4 patients who were rituximab naive responded. Multivariate analysis including IPI, ECOG PS, stage, LDH, # of extranodal sites, age, sex, # of prior regimens and time from diagnosis identified only time since last rituximab and tumor burden as correlated with response. Response to lenalidomide was associated with low tumor burden (52% for <50 cm2v 0% for ≥50 cm2, P=0.033, odds ratio=10.9) and longer time from rituximab to lenalidomide treatment (52% for ≥ 230 days v 6% for <230 days, P=0.031, odds ratio=6.6). Rituximab depletes normal host B-cells and the kinetics for their loss and recovery are consistent with the timing of lenalidomide activity following rituximab. This may be a basis for this effect. However other tumor/host biological factors may also play a role. Patients with favorable values for both prognostic factors (N=24) had a 67% response rate [RR] compared to a 4% RR for patients with unfavorable values (N=25; P< 0.001) and a progression free survival (ongoing) of 7.5 months v 1.9 months. Although absolute lymphocyte count was not selected as a prognostic indicator of response in the multivariate setting, a trend was evident in the univariate analysis (42% for > 0.6 × 109/L v 9% for ≤0.6 × 109/L, P=0.071). Conclusion: Tumor burden and host immune competence may determine the response of relapsed/refractory aggressive NHL to lenalidomide monotherapy.

17569 Background: Lenalidomide is an immunomodulatory drug of the IMiD class that has activity in multiple myeloma, myelodysplastic syndromes and chronic lymphocytic leukemia. We report preliminary results of two Phase II studies assessing the safety and efficacy of lenalidomide monotherapy in subjects with relapsed/refractory indolent or aggressive non-Hodgkin’s lymphoma (NHL). Methods: Subjects with indolent (study NHL-001) or aggressive (study NHL-002) relapsed/refractory NHL following ≥ 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated until disease progression. Response and progression are evaluated using cross sectional imaging by the NCI criteria. Results: 10 subjects (2 indolent (I), 8 aggressive (A)) of a planned 80 (40 in each study) have enrolled thus far. Median age is 66 (45–80) and 7 subjects are female. Indolent histology is follicular center lymphoma grade 1, 2 (n = 2) and aggressive histology diffuse large cell lymphoma (n = 7) and follicular center lymphoma grade 3 (n = 1). Median time from diagnosis to lenalidomide monotherapy is 2.9 years (1.1–10) and median number of prior treatment regimens per subject is 3 (1–6). Median duration of follow-up is 2 months. Of eight subjects (2 I, 6 A) evaluable for response at two months, three demonstrated a decrease in their tumor burden by 72% (I), 68% (A) and 52% (A), two subjects (2 A) exhibited stable disease and three subjects (1 I, 2 A) had disease progression. Six of the ten subjects (2 I, 4 A) demonstrated no Grade 3 or 4 adverse events. Grade 3 or 4 hematological adverse events (neutropenia, thrombocytopenia) occurred in four subjects including one febrile neutropenia and one of these four subjects also exhibited Grade 3 cellulitis. No tumor flare or tumor lysis has been observed to date. Conclusions: Preliminary data of lenalidomide monotherapy in relapsed and refractory NHL are encouraging. [Table: see text]

8066 Background: Lenalidomide, an immunomodulatory drug, is approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. This study was designed to assess the safety and efficacy of lenalidomide monotherapy in patients with relapsed/refractory indolent non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed/refractory indolent NHL with measurable disease after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Results: As of enrollment cut-off, 43 patients received drug and 27 were evaluable for response. The median age was 63 (43–82) and 12 were female. Histology was small lymphocytic lymphoma [SLL] (n=12), follicular center lymphoma grades 1,2 [FCL] (n=12) and nodal marginal B-cell lymphoma [NML] (n=3). Median time from diagnosis to lenalidomide was 4.3 (0.4- 24) years and median number of prior treatment regimens was 3 (1–17). Seven patients (26%) exhibited an objective response (2 complete responses (CR), 1 complete response unconfirmed (CRu) and 4 partial responses (PR)), 9 had stable disease (SD) for a tumor control rate (TCR) of 59% and 11 progressive disease (PD). Responses were produced in each of the indolent histologic subtypes studied: SLL (3/12), FCL (3/12) and NML (1/3). Since most responses develop at ≥ 4 months, additional responses may be seen in early SD patients with longer follow-up. Five patients (12%) exhibited Grade 4 neutropenia, and Grade 3 adverse events were neutropenia (16%) and thrombocytopenia (14%). Conclusion: Lenalidomide oral monotherapy is active with manageable side effects in relapsed/refractory indolent NHL. [Table: see text]

8052 Background: Lenalidomide (Revlimid), an immunomodulatory drug of the IMiDs class, is approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. This study was designed to assess the safety and efficacy of lenalidomide in patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed/refractory aggressive NHL with measurable disease after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Results: As of enrollment cut-off, 50 patients were enrolled and 49 received drug. Forty-one patients were evaluable for response. The median age was 65 (46–84) and 18 were female. Histology was diffuse large B-cell lymphoma [DLBCL] (n=21), follicular center lymphoma grade 3 [FL] (n=3), mantle cell lymphoma [MCL] (n=14) and transformed [TSF] (n=3). Median time from diagnosis to lenalidomide was 3.2 (0.4–32) years and median number of prior treatment regimens was 3 (1–7). Fourteen patients (34%) exhibited an objective response (5 complete responses unconfirmed (CRu) and 9 partial responses (PR)), 12 had stable disease (SD) for a tumor control rate (TCR) of 63% and 15 progressive disease (PD). Responses were seen in each of the aggressive histologic subtypes studied: DLBCL (5/21), MCL (6/14), FL (2/3), and TSF (1/3). Five of 11 patients (45%) with a prior stem cell transplant responded. Progression free survival although ongoing is currently > 239 (>191 - >373) days in patients experiencing CRu and > 160 (>54 - >251) days in patients with PR. Most common Grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%) while most common Grade 3 adverse events were neutropenia (22%), leukopenia (14%) and thrombocytopenia (12%). Conclusion: Lenalidomide oral monotherapy is active with manageable side effects in relapsed/refractory aggressive NHL. No significant financial relationships to disclose.

Abstract Abstract 2699 Poster Board II-675 Introduction: High-dose chemotherapy with autologous stem cell transplant (SCT) is a standard treatment option for younger patients with aggressive non-Hodgkin's lymphomas (a-NHL) who fail to respond, or relapse after initial therapy. For patients who relapse after SCT there are few effective treatment options and prognosis remains poor (Vose et al Blood. 80(8):2142–8, 1992). A second SCT was shown to achieve only marginal responses and at an increased risk of toxic death (Lenain et al Hematol J. 5(5):403–9, 2004). Therefore, new approaches are needed for treatment of patients in this poor prognostic group. Lenalidomide (Revlimid®) is an immunomodulatory agent that has shown clinical activity in treatment of several B-cell malignancies. Two phase 2 studies of lenalidomide monotherapy in patients with relapsed or refractory (R/R) a-NHL were conducted in the US (NHL-002; Wiernik et al JCO 26:4952–7, 2008) and internationally (CC-5013 NHL-003). In an extended follow-up of the NHL-002 study, the overall response rate (ORR) was 35%, which included 12% of patients with a complete response (CR), and a median duration of response (DR) lasting 10.4 months (Wiernik et al 2008 EHA. Abst: 764). Comparable efficacy was observed in the larger confirmatory, phase 2, NHL-003 study of lenalidomide in a similar patient population. The goal of this analysis was to learn the ORR and DR to lenalidomide in patients with a prior SCT. Methods: Patient data from both phase II studies were pooled for this report. Eligibility for both studies was similar – patients with R/R a-NHL, which included diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), transformed lymphoma (TL), and follicular lymphoma grade III (FL-III), with measurable disease (≥ 2 cm), and ≥ 1 prior treatment regimen. Patients received oral lenalidomide 25 mg once daily on days 1–21 of a 28-day cycle. Protocol defined treatment continued for up to 52 wks in NHL-002, or until disease progression in NHL-003. Primary endpoint was ORR; secondary endpoints included DR, progression-free survival (PFS), and safety. Results: 87 patients with a prior SCT (14 patients from NHL-002; 73 patients from NHL-003) were included in this analysis. Median age of patients was 61 yrs (range, 23–76), with a median of 4 prior therapies (range, 2–12). The ORR to lenalidomide was 39% (34/87), with 13% (11/87) CR/CRu and 26% (23/87) partial response (PR). Median PFS for all 87 patients was 3.8 months (95% CI, 2.6, 5.6) and the DR for 34 responders was 9.7 months (95% CI, 4.2, 16.3). Responses occurred in 15 of 52 patients (29% ORR; 10% CR/CRu) with DLBCL, 12 of 19 patients with MCL (63% ORR; 26% CR/CRu), and in 6 of 10 patients with TL (60% ORR; 10% CR/CRu). The table summarizes responses for patients who did not have a transplant, for those who had a SCT anytime prior to lenalidomide; as the last therapy prior to lenalidomide; and not as last therapy prior to lenalidomide. Most common grade 3 or 4 adverse events were neutropenia (44%), thrombocytopenia (33%), and anemia (9%). Eighteen (20.6%) patients discontinued treatment due to adverse events. Patients with a prior history of SCT appeared to have a significantly higher rate of thrombocytopenia, all grades (51% v 30%; P = 0.001), and grades 3 or 4 (33% v 16%; P = 0.002). Patients with a prior SCT were also more likely to experience a dose reduction/interruption due to thrombocytopenia compared with those without a prior SCT (25% v 14%; P = 0.027). Conclusions: Based on a pooled dataset from two phase II studies, oral lenalidomide monotherapy appears to be a well tolerated and active therapy resulting in durable responses in patients with R/R a-NHL who had a prior SCT. Furthermore, the potential of achieving a response to lenalidomide appears to be independent of prior history of SCT. Disclosures: Vose: Celgene: Research Funding. Off Label Use: Lenalidomide for the treatment of relapsed/refractory aggressive non-Hodgkin's lymphoma. . Czuczman:Celgene: Research Funding. Zinzani:Celgene: Research Funding. Tuscano:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pietronigro:Celgene: Employment, Equity Ownership. Ervin-Haynes:Celgene: Employment. Witzig:Celgene: Research Funding.

Abstract Background: Lenalidomide (Revlimid®), an immunomodulatory drug (IMiD®), was recently approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has demonstrated activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma while thalidomide, a less potent IMiD®, has activity in non-Hodgkin’s lymphoma as both monotherapy and in combination with rituximab. Aim: To assess the safety and activity of lenalidomide monotherapy in subjects with relapsed/refractory aggressive non-Hodgkin’s lymphoma (NHL). Methods: Subjects with relapsed/refractory aggressive NHL following at least 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated or until disease progression. Response and progression are evaluated using the IWLRC methodology. Results: As of July 25, 2006, 32 subjects of a planned 40 have enrolled and 31 have received drug. Twenty-two subjects are currently evaluable for tumor response. The median age of the 22 response-evaluable subjects is 65 (46–83) and 13 are female. Histology is diffuse large B-cell lymphoma [DLBCL] (n=12), follicular center lymphoma grade 3 [FL] (n=3), mantle cell lymphoma [MCL] (n=5) and transformed [TSF] (n=2). Median time from diagnosis to lenalidomide monotherapy is 2.3 (0.7–7) years and median number of prior treatment regimens per subject is 2 (1–6). Seven subjects (32%) exhibited an objective response (2 complete responses unconfirmed (CRu) and 5 partial responses (PR)), 6 had stable disease (SD) for a tumor control rate (TCR) of 59% and 9 progressive disease (PD). Responses were produced in each of the aggressive histologic subtypes studied: DLBCL (3/12), FL (1/3), MCL (2/5) and TSF (1/2). Five of 11 subjects (45%) with 1–2 prior treatment regimens had an objective response, as did 2 of 3 subjects (67%) who had received a prior stem cell transplant. Median time-to-response was 2 months. Grade 3 or 4 adverse events occurred in 18 of 31 (58%) subjects receiving drug. These were predominantly Grade 3 hematological events (neutropenia, thrombocytopenia) with only 4 subjects (13%) experiencing a Grade 4 adverse reaction. Conclusion: Preliminary results indicate that lenalidomide monotherapy is active with manageable side effects in relapsed/refractory aggressive NHL.

Abstract Background: Lenalidomide (Revlimid®), an immunomodulatory drug (IMiD®), was recently approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has demonstrated activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma while thalidomide, a less potent IMiD®, has activity in non-Hodgkin’s lymphoma (NHL) as both monotherapy and in combination with rituximab. Aim: To assess the safety and efficacy of lenalidomide monotherapy in subjects with relapsed/refractory indolent NHL. Methods: Subjects with relapsed/refractory indolent NHL following at least 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated or until disease progression. Response and progression are evaluated using the IWLRC methodology. Results: As of July 25, 2006, 23 subjects of a planned 40 have enrolled and received drug. Fifteen subjects are currently evaluable for tumor response. The median age of the 15 response-evaluable subjects is 64 (54–82) and 5 are female. Histology is small lymphocytic lymphoma [SLL] (n=8), follicular center lymphoma grades 1,2 [FL] (n=5) and nodal marginal B-cell lymphoma [NML] (n=2). Median time from diagnosis to lenalidomide monotherapy is 7.6 (3–14) years and median number of prior treatment regimens per subject is 3 (1–17). Two subjects (13%) exhibited an objective partial response (PR) at four months. Both responses, one FL and one NML, occurred in subjects with substantial tumor burden of 61.8 cm2 and 80.3 cm2, respectively. The 4-month time-to-response for these indolent NHL subjects is longer than the 2-month median time-to-response in aggressive NHL subjects (n=7) following lenalidomide monotherapy. Seven patients had stable disease (SD) for a tumor control rate (TCR) of 60% and 6 had progressive disease (PD). Grade 3 or 4 adverse events occurred in 9 (39%) subjects. These were predominantly Grade 3 hematological events (neutropenia, thrombocytopenia) with only 3 subjects (13%) experiencing a Grade 4 adverse reaction (all neutropenia). Conclusion: Early results of lenalidomide monotherapy in indolent NHL show evidence of activity with a safety profile similar to that established previously in other hematological malignancies.

Abstract Background: Lenalidomide (Revlimid®) in combination with dexamethasone was approved in the US on June 29, 2006 for the treatment of subjects with multiple myeloma who had received at least one prior therapy. On February 28, 2005 based upon a positive interim analysis of two pivotal placebo-controlled Phase III studies, an independent Data Safety Monitoring Board recommended the studies be unblinded and all subjects in both studies be given access to lenalidomide. In April 2005, the FDA in association with myeloma patient advocacy groups requested Celgene establish an expanded access program to make lenalidomide plus dexamethasone available to subjects with relapsed or refractory multiple myeloma while the treatment was awaiting approval. Aim: To provide lenalidomide to multiple myeloma subjects with a high likelihood of benefit and to obtain additional safety data. Methods: Subjects with relapsed or refractory multiple myeloma that received at least 1 prior therapy were eligible. Subjects received 25 mg lenalidomide plus high-dose dexamethasone in 4-week cycles until disease progression was documented, study drug was discontinued, or lenalidomide became commercially available for this indication. Results: Between September 8, 2005 and July 25, 2006, approximately 1400 subjects in the US and Canada were enrolled into the study. A data snapshot taken March 17, 2006 demonstrated that 746 subjects had been enrolled, median age was 63 years, 60% were male, and 66.5% had Stage III disease. Median time on study was 7.1 weeks (0.1–24.4) and median daily dose was 20.5 mg. At least one Grade 3 or 4 adverse event was reported in 261 (35%) of the 746 subjects. Most commonly reported Grade 3–4 events were neutropenia (7.9% of subjects), thrombocytopenia (6.0%), fatigue (3.6%), anemia (3.5%), pneumonia (3.1%) and hyperglycemia (2.0%). These most commonly reported Grade 3–4 adverse events were the same as those found in the previous pivotal studies, however, their frequencies of occurrence were lower in the current study probably due to ongoing data collection and differences in study maturity. Likewise, the most commonly reported adverse events (all grades) were the same as those reported in the two previous pivotal studies. Conclusion: Preliminary data from this expanded access program in over 1400 subjects with multiple myeloma are consistent with results from two earlier Phase III pivotal studies. The EAP of lenalidomide plus dexamethasone in multiple myeloma represents a model of how government, advocacy groups, healthcare providers and industry can work together to quickly provide treatment to subjects in need while a clearly active treatment regimen is awaiting approval.

Abstract Abstract 2738 Background: Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin's lymphoma (NHL) with poor prognosis that necessitates the development of new treatments. Lenalidomide is a unique immunomodulatory agent with antiproliferative and tumoricidal effects on MCL cells. NHL-003 was a phase II, open-label, multicenter trial for subjects with relapsed aggressive NHL that tested single-agent lenalidomide 25 mg PO days 1–21 every 28 days. The primary endpoint was overall response rate (ORR); secondary endpoints included complete response (CR) rate, duration of response (DOR), survival, and safety. At the time of the initial publication (Witzig et al. Ann Oncol.2011;22:1622–1627), MCL subgroup analysis showed an ORR of 42%; the median DOR had not been reached. The purpose of this report is to provide long-term efficacy and safety results for the MCL subgroup from NHL-003. Results: Subjects with MCL (N=57) had a median age of 68 y (range, 33–82), were predominantly male (77%) with good ECOG performance status (89% PS 0–1) and advanced-stage disease (88% stage III/IV). Subjects had received a median of 3 (range, 1–13) prior systemic therapies. According to the current central review at a median follow-up of 12.4 mo, subjects achieved an ORR of 35% (CR/CRu 12%) following lenalidomide, including a median DOR of 16.3 mo (Table 1). The ORR to single-agent lenalidomide was 44% (CR/CRu 21%) by independent assessment, with a median DOR not yet reached. Median PFS was 8.8 mo by central review and 5.7 mo according to investigators. Subjects responded quickly, with a median time to first response of 1.9 mo (central and investigator). Median DOR for subjects in CR and overall survival for all subjects have not yet been reached. The most common grade 3/4 adverse events (AEs) were neutropenia (46%), thrombocytopenia (30%), fatigue (9%), and diarrhea (5%). Other AEs included one subject with grade 1 to 2 tumor flare reaction, one subject with grade 3 deep vein thrombosis, and two subjects with second primary malignancies suspected of being related to treatment (one grade 3 squamous cell carcinoma of the skin that resolved and one grade 4 AML in a heavily pretreated individual with 5 prior cancer therapies). Conclusions: This subset analysis from a phase II study further confirms the efficacy of lenalidomide in subjects with relapsed MCL. Responders have a long DOR with manageable side effects. These results support continued investigation of lenalidomide alone or in combination for the treatment of MCL. Disclosures: Zinzani: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees. Off Label Use: This is a phase 2 clinical study of safety and efficacy for lenalidomide in patients with MCL. Czuczman:Celgene: Consultancy, Consultant Celgene Advisory Board Other. Reeder:Celgene: Mayo Clinic receives funding from Celgene to support clinical trials Other, Research Funding. Haioun:Celgene: Celgene Advisory Board Consultant Other, Consultancy. Tilly:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Pietronigro:Celgene: Employment. Ervin-Haynes:Celgene: Employment. Li:Celgene: Employment. Witzig:Celgene: Research Funding.

Abstract Abstract 1676 Poster Board I-702 Introduction Aggressive NHL (a-NHL) comprises a heterogeneous group of B-cell malignancies, each characterized by a unique histology and molecular markers. The most common types are diffuse large B-cell lymphoma (DLBCL), transformed lymphoma (TL), follicular grade III (FL-III), and mantle cell lymphoma (MCL). Although initial therapy can be effective, up to 40% of patients with DLBCL either fail to respond or relapse after initial therapy (Habermann TM et al JCO 2006), and relapses are likely among patients with MCL. For such patients survival outcomes are particularly poor with few effective treatment options available. Lenalidomide (Revlimid®), an immunomodulatory agent with anti-proliferative as well as apoptotic activity was tested in a pilot study and demonstrated a 35% overall response rate (ORR) with a median duration of response (DR) of 10.4 months (Wiernik et al 2008 EHA. Abst: 764). Based on these encouraging data, we performed a large, international, confirmatory phase 2 study to assess the safety and efficacy of single-agent lenalidomide in patients with relapsed of refractory DLBCL or MCL (CC-5013-NHL-003). Methods Patients were required to have relapsed or refractory aggressive B-cell NHL after ≥1 prior therapies and have at least one measurable lesion '2 cm. Patients received oral lenalidomide 25 mg once daily on days 1–21 of a 28-day cycle, and continued therapy until disease progression or unacceptable toxicity. Results 217 patients were enrolled and received lenalidomide with 108 (50%) DLBCL, 57 (26%) MCL, 19 (9%) FL-III, and 33 (15%) TL (Table 1). The median age was 66 yrs (range, 21–87), 97 patients (45%) had intermediate (3) or high (4–5) IPI scores, and the median time from diagnosis was 2.7 yrs (range, 0.04–20.6). Patients had received a median of 3 prior therapies (range, 1–13), and rituximab was included as a part of the prior therapy in 94% (205/217) of patients. The ORR for all 217 patients was 35% (77/217), with 13% (29/217) complete response (CR)/unconfirmed CR (CRu), 22% (48/217) partial response (PR), and 21% (46/217) with stable disease (SD). Responses were observed in all histological types (Table 1). Patients with a prior stem cell transplantation had a 37% ORR (27/73). The ORR was 28% (27/95) in those patients who were refractory to their last therapy, and 33% (38/116) in patients who were rituximab refractory (defined as <6 months response or no response). Median progression-free survival (PFS) for all patients was 3.5 months (95% CI, 2.5, 4.4) and the median DR for the 77 responders was 11.6 months (95% CI, 6.2, not reached [NR]). The primary side effect of lenalidomide was reversible myelosuppression. Grades 3 or 4 neutropenia occurred in 41%, thrombocytopenia in 19%, anemia in 9%, and leucopenia in 7% of patients. Adverse events caused dose reductions or interruptions in 44% (96/217) of patients and led to treatment discontinuation in 22% (48/217). Conclusion This international study supports earlier pilot-study results showing that lenalidomide has promising anti-tumor activity in aggressive B-cell NHL, with a predictable and treatable toxicity profile. These data warrant further evaluation of lenalidomide in combination with other regimens in the treatment of each histological subtype, and further exploration of lenalidomide in the maintenance setting. Disclosures Witzig: Celgene: Research Funding. Off Label Use: Lenalidomide in relapsed/refractory aggressive NHL. Vose:Celgene: Research Funding. Zinzani:Celgene: Research Funding. Guo:Celgene: Employment, Equity Ownership. Pietronigro:Celgene: Employment, Equity Ownership. Ervin-Haynes:Celgene: Employment. Czuczman:Celgene: Research Funding.