Observational studies and stand-alone trials indicate that patients with follicular lymphoma (FL) who experience disease progression within 24 months of front-line chemoimmunotherapy (POD24), have poor outcomes. We performed a pooled analysis of 13 randomized clinical trials of patients with FL in the pre- and postrituximab eras to identify clinical factors that predict POD24. Logistic regression models evaluated the association between clinical factors and POD24. Cox regression evaluated the association between POD24 as a time-dependent factor and subsequent overall survival (OS). A landmark analysis evaluated the association of POD24 with OS for the subset of patients who were alive at 24 months after trial registration. Patients without progression at 24 months at baseline had favorable performance status (PS), limited-stage (I/II) disease, low-risk FL International Prognostic Index (FLIPI) score, normal baseline hemoglobin, and normal baseline β2 microglobulin (B2M) level. In a multivariable logistic regression model, male sex (odds ratio [OR], 1.30), PS ≥2 (OR, 1.63), B2M (≥3 mg/L; OR, 1.43), and high-risk FLIPI score (3-5; OR, 3.14) were associated with increased risk of progression before 24 months. In the time-dependent Cox model and the 24-month landmark analysis, POD24 was associated with poor subsequent OS (hazard ratio, 4.85 and 3.06, respectively). This is the largest pooled analysis of clinical trials data validating POD24 as a robust indicator of poor FL survival and identified clinical predictors of early death and progression that can aid in building comprehensive prognostic models incorporating clinical and molecular predictors of POD24.

7513 Background: Standard treatment is lacking for patients with relapsed indolent NHL (iNHL). PI3K inhibitors reported a median PFS of < 1 y in R/R iNHL. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported a 39.4-mo median PFS in R/R iNHL patients (AUGMENT; Leonard. ASH 2018:445). Methods: MAGNIFY is a multicenter, non-registrational phase IIIb trial in patients with R/R FL grade 1-3a and MZL designed to determine the optimal duration of lenalidomide. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in patients with stable disease or better to continued R2 vs rituximab maintenance. These analyses evaluate the primary endpoint of ORR by 1999 IWG criteria for induction R2 in efficacy-evaluable patients receiving ≥ 1 treatment with baseline/post-baseline assessments. Results: At a median 16.7 mo follow-up, 370 patients (80% FL grade 1-3a; 20% MZL) were enrolled with a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab-containing). Efficacy-evaluable patients showed a 73% ORR and 45% CR (Table). Median TTR was 2.7 mo, median DOR was 36.8 mo, and median PFS was 36.0 mo. 142 of 370 patients have been randomized and entered maintenance. The most common all-grade AEs were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Grade 3/4 AE neutropenia was 34%; all other grade 3/4 AEs were < 6%. Conclusions: R2 therapy is active with a tolerable safety profile in patients with R/R FL and MZL, and in patients refractory to rituximab. Clinical trial information: NCT01996865. [Table: see text]

Introduction: Most patients with newly diagnosed FL treated with rituximab (R) alone or R + chemotherapy will experience prolonged progression-free survival and overall survival (OS), but it remains unclear what factors have the greatest influence on FL-associated and other causes of death in this patient population. We utilized individual patient data from 13 first-line randomized clinical trials from the FLASH database to perform a comprehensive multistate survival analysis to examine and quantify the relationships between clinical characteristics, treatment response, and early, intermediate, and late FL outcomes. Methods: The multistate survival analysis model defined states for "Alive after beginning Induction Treatment (TX)", "Alive after beginning Maintenance TX", "Death due to FL", and "Death from Other Causes" (Figure 1). We used the Aalen-Johansen estimator, a generalization of the Kaplan-Meier estimator, to calculate the likelihood of being in each model state and estimate the course of FL over time. Making no assumptions on the probability distributions and capable of coping with censored observations, the Aalen-Johansen estimator is a convenient and reliable nonparametric estimator for clinical data. Results: Among 7,465 FL patients with median age 56 (range 18-90) years, 49.2% were female; 28.7% Stage I-III, 71.3% Stage IV, and FLIPI was 0-1 (20.0%), 2 (36.8%), ≥ 3 (43.2%). Following initiation of induction treatment, 2-, 5- and 10-year death rates were 1.7%, 3.8%, and 5.8% due to FL, and 0.7%, 2.1%, and 4.8% from other causes (Figure 2). Death rates at 2, 5, and 10 years due to FL and other causes for subgroups based on clinical characteristics and treatment response are shown in Table 1. Notably, patients > 70 years and patients with FLIPI ≥ 3 had worse outcomes and patients achieving CR at 18, 24, and 30 months experienced improved outcomes. Conclusion: This is the largest study using data from randomized trials to quantify the impact of clinical factors on early, intermediate and late mortality by cause of death. We demonstrated that age > 70 years and FLIPI ≥ 3 were linked to increased FL-associated death and response to TX distinguished patients with favorable and poor outcomes. Future analyses should quantify the impact of predictors on the rate/time of FL outcomes in multivariable models. Disclosures Salles: Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events. Hoster:Janssen: Research Funding; Roche Pharma AG: Other: Travel Support. Hiddemann:Bayer: Research Funding; Gilead: Consultancy, Honoraria; Vector Therapeutics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria. Herold:Roche: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Gilead: Honoraria; Celgene: Honoraria. Morschhauser:Servier: Consultancy; Gilead: Consultancy; Janssen: Honoraria; Roche/Genentech: Consultancy; BMS: Honoraria; Celgene: Honoraria. Rummel:Roche Pharma AG: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Kimby:AbbVie,: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Gilead: Other: educational lectures. Vitolo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gyan:Pfizer: Honoraria. Ladetto:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Acerta: Honoraria; Sandoz: Honoraria. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Flowers:AstraZeneca: Consultancy; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; AbbVie: Consultancy, Research Funding; Optimum Rx: Consultancy; V Foundation: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Bayer: Consultancy; Gilead: Consultancy, Research Funding; TG Therapeutics: Research Funding; Denovo Biopharma: Consultancy; Acerta: Research Funding; National Cancer Institute: Research Funding; Millenium/Takeda: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Spectrum: Consultancy;

Introduction: The combination of lenalidomide + rituximab (R2) has demonstrated efficacy comparable to standard chemoimmunotherapy regimens in the frontline setting, and improved efficacy compared to rituximab monotherapy in the relapsed/refractory (R/R) setting among patients with indolent B-cell NHL. The multicenter, non-registrational phase IIIb MAGNIFY trial enrolled patients with R/R follicular, marginal zone, and mantle cell lymphomas (NCT01996865). This evaluation focuses on MCL patients, an aggressive though uncommon form of NHL, to determine the optimal duration of induction and maintenance therapy. Methods: R2 treatment includes lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk cycle 1 and q8wk cycles 3+ for 12 cycles of induction followed by 1:1 randomization to continued R2 vs rituximab maintenance in patients with stable disease or better. Rituximab refractory was defined as a best response of progressive/stable disease to rituximab-containing treatment or partial/complete response for < 6 mo following the last dose of rituximab. These analyses evaluate the interim primary endpoint of ORR by 1999 IWG criteria for induction R2 in efficacy-evaluable MCL patients receiving ≥ 1 treatment and with baseline/post-baseline assessments, including those who were rituximab refractory. Results: Seventy MCL patients were enrolled with a median age of 69.5 y (range, 51-88), 90% stage III/IV disease, 43% bulky disease, and 100% had received prior rituximab-containing therapy. At a median follow-up of 14.6 mo, efficacy-evaluable MCL patients showed a 54% ORR and 38% CR (Table). Median TTR was 2.9 mo, median DOR was 27.4 mo, and median PFS was 10.6 mo. Seventeen of 70 patients have been randomized and entered maintenance. The most common all-grade adverse events (AEs; ≥ 20%) were 45% neutropenia, 40% fatigue, 24% constipation, 24% dyspnea, 22% anemia, 21% diarrhea, and 21% nausea. Grade 3/4 neutropenia was 39%; all other grade 3/4 AEs were ≤ 10%. Conclusions: This first report of patients with R/R MCL from the MAGNIFY study showed that R2 therapy is active with a tolerable safety profile, including improving activity among patients considered sensitive to prior rituximab. Keywords: lenalidomide; mantle cell lymphoma (MCL); rituximab. Disclosures: Sharman, J: Employment Leadership Position: US Oncology; Consultant Advisory Role: Pharmacyclics, Celgene, TG Therapeutics, Genentech, Abbvie, Acerta Pharma/Astra Zeneca; Research Funding: (all institutional) Pharmacyclics, Genentech, Celgene, Acerta Pharma, Gilead Sciences, Seattle Genetics, TG Therapeutics, Merck, Takeda; Other Remuneration: Expert Testimony: Gilead Sciences. Coleman, M: Consultant Advisory Role: Medaptive Health; Stock Ownership: Medaptive Health; Research Funding: Medaptive Health; Other Remuneration: Speakers' Bureau: Medaptive Health. Yacoub, A: Consultant Advisory Role: Medadaptive; Other Remuneration: Speakers' Bureau: Medaptive Health. Melear, J: Employment Leadership Position: Medaptive Health. Fanning, S: Consultant Advisory Role: Medaptive Health; Stock Ownership: Medaptive Health; Other Remuneration: Speakers' Bureau: Medaptive Health. Kolibaba, K: Employment Leadership Position: Compass Oncology; Consultant Advisory Role: Gilead Sciences; Honoraria: TG Therapeutics; Research Funding: (all institutional) Acerta, Celgene, Cell Therapeutics, Genentech/Roche, Gilead Sciences, Janssen, Pharmacyclics, Novartis, Seattle Genetics, TG Therapeutics; Other Remuneration: Travel: TG Therapeutics. Lansigan, F: Consultant Advisory Role: Spectrum; Research Funding: Spectrum. Li, J: Employment Leadership Position: Celgene; Stock Ownership: Celgene, Medaptive. Llorente, M: Employment Leadership Position: Celgene; Stock Ownership: Celgene, Medaptive. Rummel, M: Consultant Advisory Role: Medadaptive; Honoraria: Medadaptive; Research Funding: Medadaptive; Other Remuneration: Travel: Medadaptive. Andorsky, D: Consultant Advisory Role: Medadaptive; Research Funding: Medaptive.

Background:There is a lack of standard treatment approaches for patients with relapsed indolent non‐Hodgkin lymphoma (iNHL). Current study results with PI3K inhibitors have reported a median PFS of <1 y in the relapsed/refractory setting (R/R) for patients with iNHL. Lenalidomide, an immunomodulatory agent, enhances the activity of rituximab when combined into a regimen known as R2, which has recently reported a median PFS of 39.4 mo in patients with R/R iNHL patients from the phase III AUGMENT study (Leonard. ASH 2018:445).Aims:These analyses examine the interim primary endpoint of overall response rate (ORR; 1999 IWG) for induction R2 in efficacy‐evaluable patients receiving ≥ 1 treatment and who have available baseline and post‐baseline assessments.Methods:The multicenter, non‐registrational phase IIIb MAGNIFY trial in patients with R/R follicular lymphoma (FL) grade 1–3a and marginal zone lymphoma (MZL) was designed to determine the optimal duration of lenalidomide (NCT01996865). R2 treatment includes lenalidomide 20 mg/d, d1–21/28 plus rituximab 375 mg/m2/wk cycle 1 and q8wk cycles 3+ given for 12 cycles, and is followed by 1:1 randomization in patients with stable disease or better to continued R2 vs rituximab maintenance.Results:370 enrolled patients (80% FL grade 1–3a; 20% MZL) had a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab‐containing). At a median 16.7 mo follow‐up, efficacy‐evaluable patients demonstrated a 73% ORR and 45% complete response (CR; Table). Similar efficacy results were shown for patients by histology. Overall, the median time to response (TTR) was 2.7 mo, median duration was response (DOR) was 36.8 mo, and median progression‐free survival (PFS) was 36.0 mo. According to their refractory status to rituximab at baseline, patients who were rituximab‐refractory and non‐refractory, respectively, had an ORR (CR) of 63% (40%) and 78% (47%), and median PFS of 18.1 mo and not reached. Of 370 patients who were randomized, 142 (38%) have entered the maintenance phase. The most common all‐grade adverse events were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Although the grade 3/4 adverse event neutropenia was 34%, all others were <6%.Summary/Conclusion:R2 therapy is an active treatment regimen in patients with R/R FL grade 1–3a and MZL, including patients refractory to rituximab, and with a tolerable safety profile.image

Introduction: Lenalidomide (Len) is an oral immunomodulatory agent with activity in CLL in both the front-line and relapsed settings. Recently Len has demonstrated significant improvements in PFS when studied as maintenance therapy following chemoimmunotherapy in the front-line and relapse settings (Fink, ASH 2016, Foà, ASH 2016) as well as in combination with R-fludarabine in the front-line setting (Rupert ASCO 2017, CALGB 10404). Here we present long-term follow-up of reduced-dose FCR (FCR-lite) in combination with Len followed by Len maintenance as a front-line CLL therapy.

7502 Background: Chemoresistant patients with FL and those who progress within 2 y after initial diagnosis have poor outcomes (Casulo. JCO. 2015) and highlight an unmet need. Methods: MAGNIFY (NCT01996865) is a phase IIIb, multicenter, open-label study of relapsed/refractory (R/R) NHL patients, including grades 1-3b or transformed FL (tFL). Patients receive 12 cycles of lenalidomide plus rituximab (R2); those with stable disease or better are randomized 1:1 to maintenance R2 or rituximab alone. The primary endpoint is progression-free survival (PFS). This analysis focuses on FL: double-refractory (DR) patients are refractory to both rituximab (as monotherapy or combination) and an alkylating agent, and early relapse (ER) patients progressed or relapsed within 2 y of initial diagnosis. Results: As of July 19, 2016, the R/R FL population (N = 117) included 32 (27%) DR and 43 (37%) ER patients, median ages of 64 and 65 y, respectively, mostly grade 1-3a FL (94%; 91%) and 2 tFL (1 DR; 1 ER); 72% and 49% were stage IV at study entry. Patients had a median of 2 prior regimens (DR 3; ER 2). Of ER patients, 31 had first-line R-chemo vs 12 with R-mono/other. Response rates are in Table 1. Median time to response was 2.8 mo for DR and 2.7 mo for ER patients, with median duration not reached. 1-y PFS for FL patients was 66% (DR 66%; ER 45%); 1-y PFS for ER patients with first-line R-chemo was 50% vs 27% in others. Common grade ≥3 treatment-emergent AEs for DR and ER patients were neutropenia (53%; 33%), leukopenia (9%; 12%), and lymphopenia (9%; 5%). Conclusions: R2 followed by maintenance showed favorable activity and tolerable safety profiles in FL patients who are double-refractory or had early relapse ( < 2 years) after initial diagnosis. Enrollment in MAGNIFY is ongoing. Clinical trial information: NCT01996865. [Table: see text]

Introduction: Although advanced age is a well-known adverse prognosis factor in first-line FL, with age >60 being one of the five adverse prognosis factor retained in the FLIPI score, little is known about characteristics and treatment outcomes for young patients. The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group conducted a pooled analysis to compare characteristics and treatment outcomes of young patients aged <40 to patients aged 40–60. Method: Individual patient data from 18 randomized first-line trials included in the FLASH database were obtained for 4249 patients aged <60. Early disease outcomes were evaluated by complete response rate at 24 and 30 months after enrollment (i.e., initiation of induction treatment; CR24 and CR30). Time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were defined in the primary FLASH study (Shi Q et al., JCO 2016). Multivariable stratified Cox models and logistic regression with generalized estimating equation were used to assess the associations between age <40 and outcomes. Variables adjusted were FLIPI risk group, rituximab use and performance status (PS). Results: Among 4249 patients included in 18 trials, 673 (16%) were <40 and 3576 (84%) 40–60. The two groups were similar in Ann Arbor stage, FLIPI risk group, use of rituximab, ECOG PS group (0–1 or ≥2), LDH value, Hb and B2-microglobulin at baseline. Young patients differed significantly only in the number of involved nodal areas (≥5 in 73% of young patients vs 66%, p = 0.0021). The two groups had similar CR24 (32% vs 29%, p = 0.32), CR30 (31% vs 30%, p = 0.57), 5-year estimates for PFS of 44% (95% CI = 41–49 for young patients and 43–46 for patients 40–60) (p = 0.30) and TTP (median TTP 3.9 y vs 4.0 y, HR = 0.96, 95% CI = 0.86–1.08, p = 0.52). OS was significantly higher for young patients with 5-year estimates of 88% (95% CI = 85–90) versus 84% (95% CI = 83–86) (p = 0.003). After adjusting with FLIPI risk group, rituximab use and PS, age <40 was a significant predictor of OS, but not of PFS, TTP or achievement of CR30. Of note, for patients having received rituximab in their first line treatment (n = 1846), patients <40 (n = 265) and patients aged 40–60 (n = 1581) had respective 5-year estimates for PFS of 54% (95% CI = 48–62) and 54% (95% CI = 51–57) (p = 0.70) and for OS of 96% (95% CI = 94–99) versus 90% (95% CI = 88–91) (p = 0.0004) (Figure). No significant difference in OS was observed between the 2 groups for patients not having received rituximab in first line. These data suggest that among patients treated with rituximab, despite an identical PFS, survival outcomes were statistically higher in the <40 group compared to 40–60. Keywords: follicular lymphoma (FL); prognostic indices.

Background:Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods:We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results:A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions:In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.

Abstract Background:Lenalidomide is an immunomodulatory agent with direct and immune-mediated mechanisms of action, as well as clinical activity in NHL. Recent studies in frontline and relapsed/refractory NHL show high activity for lenalidomide plus rituximab (R2), supporting further study of this combination. Methods: MAGNIFY (NCT01996865) is a phase IIIb, multicenter, open-label study of subjects with grades 1-3b FL (including transformed lymphoma [TL]), MZL, or MCL who received >=1 prior therapy and had stage I-IV, measurable disease (>1.5 cm). Subjects received 12 cycles of R2 induction, consisting of oral lenalidomide 20 mg/day, days 1-21 per 28-day cycle (d1-21/28) plus intravenous rituximab 375 mg/m2, days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 3, 5, 7, 9, and 11 (28-day cycles). Subjects with stable disease (SD) or better after induction were then were randomized 1:1 to R2 vs. rituximab maintenance. Stratification to the 2 maintenance arms was based on histology (FL grade 1-3b and TL vs. MZL vs. MCL), number of prior lines of antilymphoma therapy (<=2 vs. >2), and age (<65 vs. >=65 years).Maintenance R2 consisted of lenalidomide 10 mg/day, d1-21/28, cycles 13-30 plus rituximab 375 mg/m2, day 1 of cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 (Arm A). Rituximab maintenance alone was on the same schedule (Arm B). Subjects receiving R2 maintenance after 18 cycles are eligible to continue maintenance lenalidomide monotherapy 10 mg/day, d1-21/28 (optional per subject and/or investigator discretion) until disease progression as tolerated. The primary endpoint isprogression-free survival (PFS) comparing maintenance arms using a two-sided test with alpha=0.05 and HR=0.67. Secondary endpoints include safety, overall survival, and response rates. Efficacy is evaluated per modified 1999 IWG criteria and safety per NCI CTCAE version 4.03. Results: As of Jan 11, 2016, 135 subjects have been enrolled, including 91 (67%) with FL, 24 (18%) with MZL, 19 (14%) with MCL, and 1 (1%) with TL. At the time of enrollment, subjects had a median age of 66 years (range, 41-91); 81% had stage III/IV disease. Subjects had received a median of 2 prior therapies (range, 1-10), with 36% refractory to rituximab (defined as SD/PD to or PR/CR for <6 months with prior rituximab). The most common prior regimens were rituximab (41%), BR (25%), R-CHP (14%), R-CHOP (11%), and R-CVP (7%). At data cut-off, 45 (33%) subjects discontinued treatment before the maintenance period. Primary reasons for discontinuation of lenalidomide and/or rituximab, respectively, were due to AEs in 16 (12%) and 14 (10%) subjects, PD in 15 (11%) subjects for either treatment, withdrawal by subject in 6 (4%) and 7 (5%) respectively, and death 3 (2%) in either treatment. In the safety population (n=124), treatment-emergent adverse events (AE) during induction that led to dose reduction/interruption of lenalidomide or rituximab occurred in 55% or 24% of subjects, respectively, mainly due to neutropenia for lenalidomide and infusion-related symptoms for rituximab. The most common grade 3/4 AEs during induction were 27% neutropenia, 9% leukopenia, 6% thrombocytopenia, and 5% fatigue. 11 subjects have died (5 due to PD, 3 AEs, 3 other). At a median duration of 23.1 weeks (range, 0.1-51.1) of induction, 90 subjects were evaluable for response. Best responses to induction were 56 (62%) subjects with ORR, 8 (9%) CR, 12 (13%) CRu, 36 (40%) PR, and 22 (24%) SD. Responses with R2 treatment were observed in all histologies (Table 1). At data cut-off, 19 subjects have completed induction and 18 have proceeded to maintenance (n=7 R2, n=11 rituximab alone). Continued study and follow-up are ongoing to enroll more subjects in the induction and maintenance arms. Conclusions: R2 induction therapy shows favorable activity and a tolerable safety profile in subjects with advanced-stage, relapsed/refractory FL, MZL, MCL, and TL. Continued study is ongoing to determine the effect of R2 vs. rituximab maintenance following 1 year of R2 induction. Disclosures Andorsky: Gilead: Research Funding; Celgene: Consultancy, Research Funding; CTI: Research Funding. Yacoub:Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Alexion: Honoraria. Bitran:Oncology Specialists: Employment. Melear:Texas Oncology: Employment. Foon:Celgene: Employment. Rizvi:Celgene: Employment, Equity Ownership. Llorente:Celgene: Employment. Li:Celgene: Employment, Equity Ownership. Sharman:Genentech: Consultancy; Celgene: Consultancy; TG Therapeutics: Consultancy; Gilead: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy.

TPS8606 Background: Combination of the immunomodulatory agent lenalidomide (Revlimid) with rituximab (R2) is a promising therapeutic option for patients with R/R NHL. As frontline therapy, R2 provided a 90% overall response rate (ORR) in patients with follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (Fowler, Lancet Oncol, 2014) and 89% ORR in MCL patients (Ruan, ASH, 2014). In phase 2 trials of R2, patients with R/R MZL, FL, and MCL achieved ORRs of 80% (55% complete response [CR]), 73% (36% CR), and 57% (36% CR), respectively (Raderer, EHA, 2014; Leonard, ASCO, 2012; Wang, Lancet Oncol, 2012). These trials support further investigation of R2 therapy in R/R NHL. Methods: The efficacy and safety of 12 cycles of combination R2 for induction with randomization to R2 (Arm A) vs R (Arm B) maintenance will be compared in R/R FL, MCL, or MZL patients as part of the phase 3b MAGNIFY trial. Approximately 500 patients will be randomized 1:1 to 28-day (d) treatment cycles (C). Both patient groups will receive R2 induction with lenalidomide (20 mg/d on d 1-21; 12 C) + R (375 mg/m2 on d 1, 8, 15, 22 in C1; d1 of C 3, 5, 7, 9, 11). Patients in Arm A will receive R2 maintenance with lenalidomide (10 mg/d on d 1-21; C 13-30) + R (375 mg/m2 on d1 of every other C from 13 to 29), followed by lenalidomide (10 mg/d on d 1-21) until progression. Following 12 cycles of induction with R2, patients in Arm B will receive maintenance R (375 mg/m2 on d1 of every other C from 13 to 29). Eligibility criteria include R/R FL grades 1-3b, transformed FL, MZL, or MCL; previous systemic therapy; ≥ 1 measurable lesion; and adequate bone marrow, liver, and renal function. Progression-free survival is the primary endpoint. Secondary endpoints include rate of CR/CR unconfirmed (CRu), overall survival, ORR, duration of response, duration of CR/CRu, and safety. An exploratory endpoint, health-related quality of life will be measured using the FACT-Lym questionnaire. The MAGNIFY trial is currently enrolling; 38 patients have been enrolled as of January 30, 2015 (NCT01996865). Clinical trial information: NCT01996865.

7013 Background: Genetic aberrations detected by fluorescence in situ hybridization (FISH) and cytogenetic (CG) testing provide prognostic information for CLL pts. The identification of genetic abnormalities has particular relevance in choosing immunochemo- or kinase inhibitor therapies, SCT or clinical trial. Here, we analyze factors influencing decisions to perform FISH or CG testing. Methods: Connect CLL is a large, prospective, longitudinal, multicenter, observational registry of 1494 CLL pts at 179 community (n=1,311), 17 academic (n=155), and 3 government (n=28) sites. Pts were enrolled within 2 months of initiating any line of therapy (LOT). Univariate (UV) and multivariate (MV) logistic regression analyses were conducted to identify characteristics associated with a decision to perform genetic testing at LOT1 and at LOT≥2. Results: FISH or CG was performed at study enrollment in 861/1,494 (58%) pts (36% CG, 49% FISH, 28% both). 65% of 889 pts were tested for FISH/CG prior to LOT1, 50% of 260 in LOT2, 45% of 345 in LOT>3. Of 861 pts tested at enrollment, 29% had FISH/CG retested with a subsequent LOT. In UV analyses (14 predictors), FISH/CG were more often performed at academic sites (p .005), in pts age ≤75 (p .0002), at enrollment at LOT1 vs. LOT ≥2 (p < .0001), in private insurance pts (p .002) and Rai stage ≥2 (p<.0001). Table 1 describes independent predictors of performing genetic testing stratified by LOT and practice setting. Conclusions: Our results indicate that only a fraction of CLL pts are tested/re-tested for genetic alterations by FISH/CG. Given the significance of identifying del17p or complex CG in selecting each LOT, these results indicate a need for increased awareness of the importance of this testing. MV analysis: Predictors of FISH/CG. Time point/Practice setting Covariate OR 95% CI LOT1/All sites Academic vs community-govt site 1.76 1.03-2.99 White vs other 1.90 1.13-3.17 Private insurance 1.44 1.08-1.92 LOT1/Community-Govt sites White vs other 2.40 1.26-4.58 Age≤75 vs. < 75 1.44 1.01-2.05 RAI stage ≥2 vs. 1 1.52 1.07-2.14 LOT≥2:/All sites White vs other 0.34 0.17-0.68 Age≤75 1.45 1.01-2.07 LOT≥2/Community-Govt sites White vs other 0.41 0.16-1.04 Age≤75 1.65 1.05-2.61 RAI stage ≥2 1.74 1.12-2.71

Fludarabine, cyclophosphamide, and rituximab (FCR) remains the standard of care for fit chronic lymphocytic leukemia (CLL) patients requiring first therapy. However, side effects can be significant, and patients with poor risk features have inferior outcomes. The purpose of this study was to evaluate reduced‐dose FCR (FCR‐Lite) plus lenalidomide (FCR2) followed by lenalidomide maintenance as a strategy to shorten immunochemotherapy in untreated CLL. Patients received four to six cycles of FCR2. Patients who were minimal residual disease (MRD) negative in peripheral blood (PB) and bone marrow (BM) initiated 12 months of lenalidomide maintenance after either four or six cycles (based on MRD status). The primary study endpoint was the complete response (CR) rate after four cycles of FCR2. Twenty patients were evaluable. After four cycles of FCR2, response rates were: CR, 45.0%; CR with incomplete blood count recovery (CRi), 5.0%; partial response (PR), 45.0%; and stable disease (SD), 5.0%. BM and PB samples from 27.8% and 52.9% of patients, respectively, were MRD negative. After six cycles, response rates were: CR, 58.3%; CRi, 16.7%; and PR, 25.0%. BM and PB samples from 50.0% and 72.7% of patients, respectively, were MRD negative. Overall, 75% of evaluable patients achieved a CR or CRi following FCR2. After 17.4 months of median follow‐up, one progression and one death occurred. Our findings suggest that FCR2 combines encouraging clinical activity with acceptable toxicity in previously untreated CLL. Lenalidomide can be safely added to FCR and may reduce chemotherapy exposure without compromising outcomes. Am. J. Hematol. 90:487–492, 2015. © 2015 Wiley Periodicals, Inc.

We performed a phase II study of belinostat in patients with acute myeloid leukemia (AML). In this open label phase II study (NCT00357032), patients with relapsed/refractory AML, or newly diagnosed patients with AML over the age of 60, were eligible. Belinostat was administered intravenously (IV) at a dose of 1000 mg/m(2) daily on days 1-5 of a 21-day cycle until progression or unacceptable toxicity. The primary endpoint was complete response (CR) rate, with secondary endpoints of overall response rate (CR + partial response [PR]), time to treatment failure (TTF), overall survival and safety. Twelve eligible patients with AML were enrolled, of whom six had received at least one prior line of therapy. No CR or PR was seen. Four patients had stable disease for at least five cycles. Grade 3 non-hematological toxicities occurred in four patients. Belinostat as monotherapy has minimal single-agent effect in AML on this dosing schedule.

TPS8617 Background: Immunomodulation with lenalidomide (L) + rituximab (R) is a promising treatment approach for patients (pts) with indolent NHL. In indolent NHL, frontline L+R provided a 90% overall response rate (ORR) and 64% complete response/complete response unconfirmed (CR/CRu) (Fowler, ASH, 2012). In phase 2 trials of L+R in relapsed/refractory (R/R) disease, pts with mantle-cell lymphoma (MCL) achieved 57% ORR and 36% CR (Wang, Lancet Oncol, 2012); pts with follicular lymphoma (FL) treated with L+R had a higher response rate (73% ORR, 36% CR) compared with those receiving L alone (51% ORR, 13% CR; Leonard, ASCO, oral presentation, 2012). Methods: The phase 3b MAGNIFY study will compare the efficacy and safety of 12 cycles of combination L+R for induction with randomization to L+R (Arm A) vs R (Arm B) maintenance in pts with R/R FL, MCL, or marginal zone lymphoma (MZL). Target enrollment is ~500. Pts will be randomized 1:1 to 28-day (d) treatment cycles. In both arms, pts will receive induction L (20 mg/d on d 1-21; 12 cycles) + R (375 mg/m2 on d 1, 8, 15, 22 in cycle 1; d1 of cycles 3, 5, 7, 9, 11). In Arm A, pts will receive maintenance L (10 mg/d on d 1-21; cycles 13-30) + R (375 mg/m2 on d1 of every other cycle from 13-29), followed by L (10 mg/d on d 1-21) until progression. Following 12 cycles of induction with L+R, pts in Arm B will receive maintenance R (375 mg/m2 on d1 of every other cycle from 13- 29). Eligible pts must have R/R grade 1, 2, or 3a FL, MZL, or MCL; have completed previous systemic therapy; have ≥1 measurable lesion; and have adequate bone marrow, liver, and renal function (moderate renal impairment acceptable). The primary endpoint is progression-free survival. Key secondary endpoints include rate of CR/CRu, overall survival, ORR, duration of response, duration of CR/CRu, and safety. Health-related quality of life, as measured by the FACT-Lym questionnaire, will be assessed as an exploratory endpoint. This trial is currently enrolling pts. Clinical trial information: NCT01996865.

This phase 2 study assessed the safety and efficacy of ocaratuzumab, a humanized anti-CD20 monoclonal antibody. Fifty patients with previously treated follicular lymphoma (FL) and a low-affinity genotype of FcγRIIIa received ocaratuzumab 375 mg/m2 weekly for 4 weeks. Grade 3/4/5 adverse events (AEs) were reported in 11/1/1 patients, respectively. Serious AEs were reported by 11/50 patients, and three discontinued due to AEs. One patient died from aspiration pneumonia due to possibly drug-related nausea and vomiting. Investigator-assessed response rate was 30% (15/50), including four complete responses (CR), three CR unconfirmed (CRu) and eight partial responses (PR). Investigator-assessed median Progression-free survivial (PFS) was 38.3 weeks. Ocaratuzumab's pharmacokinetic profile was similar to that reported for rituximab. Lymphocyte subset analysis showed significant, selective reduction of B-cells during and after ocaratuzumab treatment. Ocaratuzumab at this dose and schedule is active and well tolerated in patients with previously treated FL with low affinity FcγRIIIa genotypes. ClinTrials registry number: NCT00354926.

Introduction: Fludarabine, cyclophosphamide, rituximab (FCR) remains the standard of care for the treatment of newly diagnosed, fit CLL pts requiring therapy. However, the FCR side effects profile is non-trivial and CLL pts with poor risk features have inferior outcomes. Strategies aimed at minimizing toxicity without compromising efficacy have been reported including modifications of the optimal dosing and duration of FCR using a dose-reduced approach (Foon et al, “FCR lite”) or reduction in number of FCR cycles based on MRD status (Strati et al). In the era of biological agents, both preclinical and clinical data have shown the efficacy of lenalidomide (Len) in CLL likely through its role as an immunomodulator and interference with interactions between CLL and its microenvironment. In CLL, Len presents a clinical opportunity both in combination with chemotherapy and as maintenance strategy. This was the rationale for our trial using Len in combination with FCR and as maintenance to improve outcomes and shorten therapy.