ALBERT

Description: Introduction: PI3Kδ signaling is critical for the proliferation, survival and homing/tissue retention of malignant B cells. Idelalisib is a first-in-class, highly selective, oral inhibitor of PI3Kδ recently approved for the treatment of relapsed CLL in combination with R. This report summarizes the long-term follow-up of the Phase 1 combination experience of idelalisib with anti-CD20 antibodies. Methods: This Phase 1 study evaluated idelalisib for relapsed/refractory CLL continuously given at 100 mg BID (4 of the pts receiving R) or 150 mg BID (all other pts) in combination with a total of 8 infusions of rituximab (R, 375 mg/m2 weekly x 8), or a total of 12 infusions of ofatumumab (O, 300mg initial dose either on Day 1 or Day 2 relative to the first dose of idelalisib, then 1,000 mg weekly x 7, then 1,000 mg every 4 wks x 4). Pts on treatment after 48 weeks were eligible to continue idelalisib on an extension study. Clinical response was evaluated according to published criteria (Hallek 2008; Cheson 2012). Results: 40 pts (12F/28M) with a median (range) age of 66 (43-87) years and a WHO performance status of 0 (24, 60%) or 1 (16, 40%) were enrolled. 19 pts received idelalisib in combination with R and 21 with O. Adverse disease characteristics (n, %) included Rai Stage III/IV (20, 50%), bulky lymphadenopathy (23, 58%), refractory disease (15, 38%), multiple prior therapies (median 2, range: 1-9). Almost all pts (39, 98%) had at least 1 prior therapy containing R, and 3 of the 21 pts (14%) receiving idelalisib + O had received prior O. 63% of the pts receiving idelalisib + R, and 48% of the pts receiving idelalisib + O were refractory to R. Prior therapies also included alkylating agents (31, 78%, [bendamustine: 20, 50%]) and purine analogs (31, 78%, [fludarabine: 28, 70%]). Data available from 39 pts showed that 11 (28%) pts had evidence of del(17p) and/or TP53 mutations and 30 (75%) had unmutated IGHV. As of 7/15/2014, the median (range) treatment duration was 18 (0-44) months. 23 (58%) pts have completed the primary study and enrolled into the extension study. Primary reasons for study discontinuation (as reported by investigators) included disease progression (14, 35%), adverse events (AEs) (12, 30%), investigator request (3, 8%), withdrawal of consent (n=1), BMT (n=1). There were a total of 8 deaths on study: 2 deaths occurred after disease progression, and 6 pts died because of AEs (all assessed as unrelated/unlikely related to idelalisib by investigators). A total of 4 pts (10%) were continuing idelalisib treatment on the extension study at time of analysis. Selected treatment-emergent AEs (any Grade/≥Gr 3, regardless of causality) included diarrhea/colitis (55%/23%), cough (40%/3%), pyrexia (40%/3%), dyspnea (30%/3%), fatigue (25%/0%) nausea (25%/0%), rash (20%/0%), pneumonia (20%/18%), and pneumonitis (8%/5%). Elevation of liver transaminases (TA, any Grade/≥Gr 3) was seen in 30%/10%. Re-exposure to idelalisib after resolution of TA elevation generally was successful; only 1 patient discontinued the study because of (recurrent) TA elevation. Other AEs leading to study discontinuation and reported as possibly/probably related to idelalisib included diarrhea/colitis (4, 10%), pyrexia (n=1), interstitial lung disease (n=1), pneumonia (n=1), rash (n=1), psoriasis (n=1). Secondary malignancies leading to discontinuation (all reported as unrelated) were breast cancer (n=1), recurrent colon cancer (n=1), AML (n=1). There was no obvious overall difference in the toxicity reported for pts receiving idelalisib with rituximab compared to those with ofatumumab. The ORR (N=40) was 83% (33/40), with 2 CRs (5%) reported. Median PFS (N=40) and duration of response (DOR) (n=33) were 24 months. Median (range) time to response was 1.9 (range 1.7-16.9) months. Median overall survival (OS) has not been reached with a KM estimate for OS of 80% at 24 months. For the 11 pts with del(17p) and/or TP53 mutations, the response rate was 73%, and the median PFS and DOR were 20 and 24 months, respectively. Conclusions: Combinations of idelalisib with anti-CD20 antibodies such as R or O represent non-cytotoxic regimens with acceptable safety profiles and considerable activity resulting in durable tumor control in pts with relapsed/refractory CLL, including those with high risk factors such as del(17p) or TP53 mutations. A Phase 3 trial evaluating the efficacy of idelalisib in combination with ofatumumab is ongoing (NCT01659021). Disclosures Furman: Gilead Sciences: Research Funding. Off Label Use: Zydelig is a kinase inhibitor indicated for the treatment of patients with: 1) Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities; 2) Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies; and 3) Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.. de Vos:Gilead Sciences: Research Funding. Barrientos:Gilead Sciences: Research Funding. Schreeder:Gilead Sciences: Research Funding. Flinn:Gilead Sciences: Research Funding. Sharman:Gilead Sciences: Research Funding. Boyd:Gilead Sciences: Research Funding. Fowler:Gilead Sciences: Research Funding. Leonard:Gilead Sciences: Research Funding. Rai:Gilead Sciences: Research Funding. Kim:Gilead Sciences: Employment, Equity Ownership. Viggiano:Gilead Sciences: Employment, Equity Ownership. Jahn:Gilead Sciences: Employment, Equity Ownership. Coutre:Gilead Sciences: Research Funding.

Description: The results of gene expression profiling (GEP) and immunohistochemical studies indicate that survival is worsened by macrophages (MΦ) in the tumor microenvironment of various B-cell lymphomas including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Tumor-associated macrophages (TAMs) are known to be different from other types of MΦ, but the effects of TAMs that worsen prognosis in B-cell lymphoma are essentially unknown, as are the mechanisms of these effects. Here, we determined the phenotype and effects of TAMs on tumor survival, proliferation, and drug resistance in B-cell lymphomas and evaluated strategies to reverse their effects. As compared to peripheral blood monocytes (Mo) from normal donors (ND), Mo from FL patients were differentiated less into M1 MΦ (defined as CD68+CD163loCD206loCD86hi) by culture with CSF-1 for 5 days followed by IFN-g + LPS for 2 days more. In contrast, Mo from FL patients and ND were differentiated similarly into M2 MΦ (defined as CD68+CD163hiCD206hiCD86lo) by culture with CSF-1 followed by IL-4. Consistent with this, MΦ gene signatures from FL tumors were more similar to previously-described signatures of M2 rather than M1 MΦ (Martinez et al, J Immunol, 2006, 177(10):7303-11). In co-culture, primary FL tumor cells and lymphoma cell lines (including RL, a transformed FL cell line; Granta 519, a mantle cell lymphoma (MCL) cell line; and Raji, a Burkitt lymphoma cell line) induced differentiation of Mo into MΦ. Differentiation could be prevented by CS4 monoclonal antibody (mAb), a fully human IgG1 anti-human CSF-1R mAb (ImClone/Eli Lilly), but not isotype control Ab. Elevated levels of CSF-1 in culture supernatants after addition of CS4 mAb and real-time PCR of tumor cells suggested secretion of CSF-1 by lymphoma cells. Spontaneous apoptosis of primary FL and MCL tumor cells, determined by Annexin V and propidium iodide staining, was significantly reduced by co-culture with ND Mo (p

Description: Background: PTCLs are a rare, heterogeneous group of neoplasms that account for 12% of non-Hodgkin lymphomas (NHL) in Europe and USA and 〉20-25% in Asia. There is no consensus on optimal treatment and 5-year survival rates remain

Description: The SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18). Of VEPEMB patients, 31 had early-stage disease (stage 1A/2A) and received VEPEMB 3 times plus radiotherapy. Median follow-up was 36 months. Complete remission (CR) rate (intention-to-treat) was 74% and 3-year overall survival (OS) and progression-free survival (PFS) were 81% and 74%, respectively. A total of 72 patients had advanced-stage disease (stage 1B/2B/3 or 4) and received VEPEMB 6 times. CR rate was 61% with 3-year OS and PFS of 66% and 58%, respectively. Of patients achieving CR, 13% with early-stage and 5% with advanced-stage disease progressed. Overall treatment-related mortality was 7%. In patients treated with curative intent with VEPEMB, ABVD, and CLVPP (n = 157), CR linked to several factors in univariate analysis. In a Cox regression model only, obtaining CR remained significant for OS and CR plus comorbidity and age for PFS. RS-EBV status had no significant effect on outcome.

Description: Key Points Donor T-Rapa cells were composed of Th1 and Th2 effectors with a reproducible gene expression profile. Preemptive T-Rapa donor lymphocyte infusion was safe and associated with donor engraftment without excessive GVHD.

Description: Introduction. Cytokine release syndrome (CRS) and neurotoxicity (NT)(also known as immune effector cell-associated neurotoxicity syndrome or ICANS) are commonly observed after chimeric antigen receptor (CAR) T-cell therapy. While the clinical features of CRS have been extensively described, limited data exists for NT. Here, we report clinical and radiological features of NT after standard of care (SOC) axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Methods. Pts with r/r LBCL treated with SOC axi-cel at MD Anderson Cancer Center between 01/2018 and 04/2019 were included in the study. All pts received anti-seizure prophylaxis with levetiracetam starting on the day of axi-cel infusion for 30 days. CRS and NT were prospectively graded according to CARTOX criteria (Neelapu et al, Nat Rev Clin Oncol, 2018). Association between continuous variables were assessed using the bivariate Pearson correlation. Results. Ninety-five pts were included in the study, 72 (76%) with diffuse LBCL, 17 (18%) with transformed follicular lymphoma, and 6 (6%) with primary mediastinal LBCL. Median age was 60 (range, 18-85), 71 (75%) were male. Median number of previous therapies was 4 (range, 2-15), 26 (27%) had a previous autologous stem cell transplant (SCT), and 1 (1%) a previous allogeneic SCT. Eight (8%) pts had prior central nervous system lymphomatous involvement (parenchymal in 5), and 39 (41%) had prior neurological and/or psychiatric medical history. After axi-cel infusion, NT of any grade was observed in 65 (68%) pts, grade ³3 in 46 (48%)(Table). No significant association was observed between above outlined baseline characteristics and development of NT. Median time from axi-cel infusion to NT onset was 5 days (range, 0-25 days) and median duration was 6 days (range, 1-52 days); no new onset/recurrent NT was observed beyond day 30. Among the 65 pts who developed NT, a CT head without contrast was performed in 48, and was not evaluable in 2 because of motion artifacts. Among the 46 evaluable scans, 1 (4%) was abnormal as compared to baseline, and showed new onset cortical edema (non-diffuse but symmetrical). An MRI brain with contrast was performed in 36 pts, but was not evaluable in 10 because of lack of baseline, motion artifacts or differences in imaging sequences. Among the 26 evaluable scans, 15 (58%) showed abnormal findings, including autoimmune encephalitis-like, characterized by symmetric white matter changes of the pons and hippocampus (6; Fig. A), stroke-like (4; Fig. B), LMD-like (3; Fig. C) and PRES-like (2; Fig. D), with concomitant cortical edema in 5. EEGs were performed in 52 pts (〉1/pt, for a total of 116 EEGs) and were abnormal in 47 (90%). Focal and/or diffuse slowing was the most common abnormality (isolated finding in 35 [73%] pts), while epileptiform discharges and/or non-convulsive status epilepticus (NCSE) were observed 12 (27%) pts. A lumbar puncture was performed in 12 pts: median white blood cell count was 2 cells/µL (range, 0-6), median protein 47 mg/dL (range, 13-600), median glucose 69 mg/dL (range, 30-111), and cytology was positive for malignant cells in 2 (7%) pts. Convulsive seizure was observed in 4 (6%) pts and 10 (15%) received additional anti-seizure therapy for convulsive or non-convulsive seizures. Among the 65 pts with NT, dexamethasone up to 20 mg IV Q6H was given to 42 (65%) pts, methylprednisolone 1000 mg IV daily to 12 (18%), and tocilizumab to 64 (98%; during CRS or CRS with concurrent NT). Overall, 93 (98%) pts developed CRS, grade 〉3 in 27 (28%). A significantly higher rate of NT of any grade (96% vs 57%, p3 (81% vs 35%, p3 CRS. After a median follow-up of 4 months, 6-month progression-free (PFS) and overall survival (OS) rates were 60% and 65%, respectively. Significantly shorter 6-month PFS (46% vs 80%, p=0.02) and OS rates (56% vs 83%, p=0.01) were observed among pts developing NT of any grade. Conclusions. Our results suggest that multiple radiological patterns of NT after axi-cel are possible in r/r LBCL pts, MRI being more sensitive than CT scan for their detection. NCSE is a common event, supporting the use of seizure prophylaxis and EEGs for evaluation of these pts. Pts with NT experience a worse outcome, and additional clinical and biological predictors of NT will be analyzed and presented at the meeting. Figure Disclosures Nastoupil: Spectrum: Honoraria; Janssen: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria. Westin:47 Inc: Research Funding; Novartis: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; MorphoSys: Other: Advisory Board; Unum: Research Funding; Curis: Other: Advisory Board, Research Funding; Genentech: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding; Janssen: Other: Advisory Board, Research Funding. Fowler:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lee:Seattle Genetics, Inc.: Research Funding. Parmar:Cellenkos Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang:Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Dava Oncology: Honoraria. Pinnix:Merck: Research Funding. Hawkins:Novartis Pharmaceuticals: Other: advisory panels. Neelapu:Precision Biosciences: Consultancy; Novartis: Consultancy; Allogene: Consultancy; Incyte: Consultancy; BMS: Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Karus: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Cell Medica: Consultancy; Unum Therapeutics: Consultancy, Research Funding; Pfizer: Consultancy. Chi:Kite, A Gilead Company: Consultancy, Honoraria, Other: Kite Patient Management Advisory Board.

Description: Introduction: High standardized uptake value (SUV) on FDG PET scan in follicular lymphoma (FL) suggests aggressive disease and possible transformation to diffuse large B-cell lymphoma. Schoder et al, J Clin Oncol, 2005, reported that SUV 〉10 predicted aggressive lymphoma with 〉80% certainty and SUV 〉13 with 〉90% certainty. However, it is unknown whether the maximum SUV (SUVmax) on FDG PET scan at baseline, suggesting the possibility of focal aggressive or transformed disease, has prognostic value in FL. Here, we determined the prognostic value of SUVmax on baseline FDG PET scan in patients with advanced stage FL treated uniformly with R-CHOP chemoimmunotherapy at initial diagnosis. Methods: We reviewed medical records of all patients with stage III or IV FL who had FDG PET scan at initial diagnosis and were treated with R-CHOP chemoimmunotherapy at MD Anderson Cancer Center between January 2001 and December 2012. Patients with histological diagnosis of concurrent diffuse large B-cell lymphoma were excluded. Results: For the 225 patients studied, the median age was 57 years (range, 20-82). 83 (37%) patients were 〉= age 60, 137 (61%) had grade 1 or 2 FL, and 88 (39%) had grade 3A (n=57, 25%) or 3B (n=31, 14%). The Ki-67 score was 40% for 56 (40%) patients. FLIPI risk groups were 54 patients (24%) low, 74 (33%) intermediate, and 97 (43%) high. GELF criteria were met in 133 (59%) patients. Tumor bulk of 〉= 6 cm was seen in 97 (43%) patients. The absolute lymphocyte count (ALC) was normal or high in 155 (69%) patients and low in 70 (31%). Sixty-nine (31%) patients received rituximab maintenance. There was no correlation between baseline SUVmax on FDG PET scan and Ki-67 score (Pearson correlation co-efficient of 0.168). The overall and complete response rates were 96% and 87%, respectively. The median follow-up time was 66 months. At 5 years, progression-free survival (PFS) was 85% and overall survival (OS) was 90%. Male gender, stage IV, high risk FLIPI, presence of GELF criteria, high beta-2 microglobulin, and low ALC were associated with significantly inferior PFS and OS (p= 60 was associated with inferior OS but not PFS. Rituximab maintenance was associated with improved PFS but not OS. On baseline FDG PET scan, median SUVmax was 13.7 and the SUVmax range was 1.5-42.1. 105 (47%) patients had SUVmax 13. Patient characteristics including age, gender, histological grade, Ki-67 score, and FLIPI risk groups were not significantly different between the two SUVmax populations (p〉0.05). The overall response rates were 94% and 96% for the SUVmax 13 groups, respectively. The complete response rate was 87% in both groups. At 5 years, the PFS and OS were not significantly different between the low and high SUVmax groups (61% vs 63% for PFS, p=0.98 and 90% vs 89% for OS, p=0.63). PFS and OS were not significantly different even when the patients were grouped into SUVmax 10 (p=0.9 and 0.61, respectively) or when other cut-offs were used. SUVmax was also not predictive of PFS and OS when only the patients meeting GELF criteria were analyzed. Conclusions: In this large cohort of advanced stage FL patients treated uniformly with R-CHOP chemoimmunotherapy, SUVmax on baseline FDG PET scan was not predictive of clinical outcome or correlated with other features. It is possible that the doxorubicin-based chemotherapy regimen may have benefited patients with high SUVmax who may have underlying aggressive or undiagnosed transformed disease. It remains to be determined whether SUVmax is predictive of clinical outcome in FL patients treated with other commonly used therapies such as rituximab monotherapy, rituximab and bendamustine, or R-CVP. Figure 1 Figure 1. Disclosures Wang: Pharmacyclics, Janssen: Honoraria, Research Funding. Westin:Novartis: Research Funding.

Description: Abstract 2456 Poster Board II-433 Murine T cells exposed to rapamycin maintain flexibility towards Th1/Tc1 differentiation; the degree to which rapamycin might inhibit human Th1/Tc1 differentiation has not been fully evaluated. In the presence of rapamycin, T cell co-stimulation and polarization with IL-12 or IFN-α permitted human CD4+ and CD8+ T cell differentiation towards a Th1/Tc1 phenotype: by intracellular flow, median percentage expression of Foxp3, IFN-γ, and T-bet was 4%, 20%, and 72%, respectively. Phospho-flow cytometry revealed that such Th1/Tc1 cells expressed activated STAT1 and STAT4 in spite of mTOR blockade; STAT activation was abrogated by PI3 kinase inhibition. Rapamycin-resistant human Th1/Tc1 cells (Th1/Tc1.R cells): (1) had increased expression of the autophagy-related gene LC3BII by gene array and protein analysis; (2) preferentially expressed anti-apoptotic bcl-2 family members (reduced Bax, Bak; increased phospho-Bad); (3) maintained mitochondrial membrane potentials; and (4) had reduced apoptosis relative to control Th1/Tc1 cells not generated in rapamycin (p=0.04). The anti-apoptotic phenotype of Th1/Tc1.R cells was abrogated by co-incubation with the autophagy inhibitor, 3-methyl adenine. The in vivo effect of the Th1/Tc1.R cells was evaluated using two xenogeneic GVHD (x-GVHD) models. First, in an LPS-induced x-GVHD model, Th1/Tc1.R cells resulted in lethality in 75% recipients; soluble TNF-α receptor therapy with etanercept reduced the frequency of lethality to 15%. Second, using a non-LPS natural history model of x-GVHD, recipients of Th1/Tc1.R cells (relative to recipients of control Th1/Tc1 cells) had increased human T cell engraftment (day 30 post-BMT, p=0.001), increased human T cell cytokine levels, increased human T cell expression of the cytotoxic degranulation molecule CD107 (p=0.05), and increased human T cell infiltration of skin, gut, and liver. In this model, lethality due to x-GVHD was also increased in Th1/Tc1.R cell recipients (lethality increased from 20% to 70%, p=0.04). We conclude that rapamycin therefore does not impair human T cell capacity for type I differentiation. Rather, by promoting autophagy rapamycin permits stable expression of T-bet and generates an anti-apoptotic Th1/Tc1 effector phenotype, thereby yielding increased x-GVHD. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1714 Poster Board I-740 Background Despite advances in therapy and a better understanding of the natural history of indolent non-Hodgkins lymphomas (NHL), the optimal treatment for newly diagnosed patients (pts) has not been determined. While several chemotherapy regimens have response rates approaching 90%, toxicity is common with standard genotoxic combinations, particularly with retreatment at relapse. Lenalidomide is approved for the treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes with del(5q) mutation. In pts with indolent relapsed or refractory NHL, treatment with lenalidomide resulted in durations of response lasting 〉 16.5 months (Witzig et al JCO in press). Rituximab has been shown to have clinical activity in indolent NHL, both as a single agent and in combination with chemotherapy. The aim of this phase II, single arm study is to evaluate the efficacy and safety of lenalidomide and rituximab in pts with untreated, stage III or IV, indolent NHL. Methods Previously untreated pts with indolent NHL and with measurable disease (〉1.5 cm), were eligible for enrollment. For each 28-day cycle, pts received lenalidomide 20mg orally once daily on days 1-21 and rituximab 375mg/m2 intravenously on day 1, for up to 6 cycles of therapy. Response was assessed after 3 cycles and at the end of therapy using the International Working Group Response Criteria (Cheson et al 1999). Results At the time of this report, the planned accrual of 30 pts is complete. Response and adverse events are reported for the first 20 patients, which included 19 pts eligible for response assessment and 1 patient, who discontinued from study prior to response evaluation, secondary to leukocytoclastic vasculitis, which occurred during cycle 1. The median age was 55 yrs (range: 38-77) and 55% were male. The 20 currently evaluable patients include10 pts with follicular lymphoma, 8 pts with marginal zone lymphoma and 2 pts with small lymphocytic lymphoma. Of 19 pts eligible for response assessment, 18 completed 6 cycles of therapy and 1 pt, who was previously treated for Hodgkin's lymphoma, withdrew consent following cycle 3. The overall response rate was 84%, which included complete responses in 15 pts (79%; 58% CR/21% CRu) and 1 patient who achieved a partial response. An additional 3 pts (16%) remain with stable disease. By completion of 6 cycles of therapy, all 10 pts with follicular lymphoma achieved a complete response to therapy. No pt experienced progression of disease. The following grade 3/4 adverse events were reported; rash (6 pts), neutropenia (4 pts), myalgia (3 pts), neuropathy (1 pt), infection (1 pt), and fatigue (1 pt). Rashes, of all grades, occurred in 10 pts, which were mostly erythematous and transient, nonrecurring events. Response and toxicity assessment for the remaining 10 pts is ongoing and will be reported. Conclusion The biologic regimen of lenalidomide and rituximab as front line therapy produces excellent overall and complete response rates in pts with indolent B cell NHL. The combination was well tolerated with a manageable toxicity profile. Disclosures Fowler: Genentech: Honoraria, Speakers Bureau; BiogenIdec: Honoraria. Off Label Use: lenalidomide and rituximab for indolent B cell non-Hodgkin's lymphoma. McLaughlin:Genentech: Consultancy, Honoraria. Hagemeister:Genentech: Honoraria, Speakers Bureau; BiogenIdec: Honoraria, Speakers Bureau; Celgene: Consultancy. Kwak:Celgene: Research Funding. Samaniego:Celgene: Consultancy.

Description: Abstract 1666 Poster Board I-692 Diffuse large B-cell lymphoma (DLBCL) is primarily treated with Rituximab – CHOP immunochemotherapy with varying results. Improved prediction at diagnosis of outcome for an individual patient remains a key goal in DLBCL management. This would allow the selection of patients who could benefit from new therapies. A large amount of data on new immunohistochemical and molecular factors has been collected in the last decade, but the International Prognostic Index (IPI) and Revised IPI are still mostly used for identification of prognostic groups. Both of these indices have important limitations. They rely on a small number of dichotomised predictive variables and patients are assigned to one of a small number of risk groups rather than giving a direct prediction, such as a predictive survival probability or a predictive median lifetime, on a continuous scale for each patient. We have developed a new prognostic index based on Bayesian survival modelling. This has allowed an increase in the number of predictive variables and removal of the need to dichotomise them. Importantly, the new index can give predictions for patients where not all of the predictive variables are observed. It can easily be modified in the future by the addition of new variables, e.g. molecular factors or new treatment regimens. The index was developed using data on a population-based cohort of DLBCL patients prospectively registered with the Scotland and Newcastle Lymphoma Group (SNLG) between 1990 and 2003. The complete data on patients' outcomes were available for 1863 from 2025 registered patients and of this cohort 1391 patients were treated with anthracycline-based chemotherapy and the new index is based on this group. Bayesian statistical inference was used with a three-component Weibull mixture model in which both the hazard multiplier and the component membership probabilities depend on the predictive covariates. The three mixture components correspond to the following three groups: patients who will suffer from primary progressive disease or relapse within one year from diagnosis; patients who will relapse at a later point; those who will have no relapse. A novel method of modelling to deal with cases with missing covariates was used. Both time to first relapse (TFR) and overall survival (OS) were modelled. The following factors were included in the current version of the model: age, sex, performance status by ECOG, clinical stage, B-symptoms, extranodal and bone marrow involvement, Hb, WBC, lactate dehydrogenase, albumin, alkaline phosphatase and urea. The new index is available in the form of a simple computer program and can predict the outcome of patients as: a predicted TFR and OS or a probability of belonging to one of the three groups. In order to check the index, the whole cohort of patients was separated randomly with stratification by IPI into a training-prediction set (2/3 of patients) and a validation-observed set (1/3 of patients). Fig 1 shows the Kaplan-Meyer plots for TRF and OS for both sets. The index was successfully validated. Our new Bayesian prognostic index for DLBCL gives more reliable predictions at diagnosis for individual patients. In future the model can be modified for new treatment regimens or factors. Presently our group is investigating this issue for patients treated with CHOP-R. Fig1 Kaplan-Meyer plots for TFR and OS in training-prediction (TFRP and OSP) and validation-observed set (TFRO and OSO). Fig1. Kaplan-Meyer plots for TFR and OS in training-prediction (TFRP and OSP) and validation-observed set (TFRO and OSO). Disclosures No relevant conflicts of interest to declare.