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Background: Lenalidomide combined with rituximab (R2) has shown complimentary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) patients with indolent non-Hodgkin lymphoma. Patients with advanced age at diagnosis are considered to be high risk, supporting post-hoc subgroup analyses by age, with a focus on patients aged ≥ 70 years from the MAGNIFY study. Methods: MAGNIFY is a multicenter, phase IIIb trial in patients with R/R follicular lymphoma (FL) grades 1-3b, transformed FL (tFL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL; NCT01996865) exploring optimal lenalidomide duration. Lenalidomide 20 mg on days 1-21 of a 28-day cycle + rituximab 375 mg/m2/week cycle 1 and then every 8 weeks starting with cycle 3 (R2) are administered for 12 cycles followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 months. Data presented here focus on induction R2 in efficacy-evaluable FL grade 1-3a and MZL patients (FL grade 3b, tFL, and MCL not included) receiving ≥ 1 treatment with baseline/postbaseline assessments. The primary end point is progression-free survival (PFS) by 1999 International Working Group criteria. Post-hoc analyses were performed by analyzing data from patients aged ≥ 70 years at time of study entry. Results: As of November 30, 2019, 393 patients have enrolled and 152 (39%) were aged ≥ 70 years. Baseline characteristics including histology, disease status, and prior treatments of patients ≥ 70 and the overall population are shown in the table. Median PFS in the ≥ 70 subgroup was 36.0 months (95% CI, 28.3-NR). Overall response rate and CR/CRu were 75% and 38%, with a median duration of response that was not reached (95% CI, 27.1-NR). Efficacy results for the overall population are shown in the table. In patients ≥ 70 the most common (≥ 20%) any-grade treatment emergent adverse events (TEAEs) were fatigue (44%), neutropenia (41%), diarrhea (34%), constipation (34%), and nausea (27%). Neutropenia (35%) was the only grade 3/4 TEAE occurring in > 10% of patients (febrile neutropenia occurred in 3 patients [2%]). TEAEs led to lenalidomide dose reduction in 69 patients (46%) and discontinuation in 40 patients (26%). Seventy-eight patients ≥ 70 (51%) completed all 12 cycles of induction treatment, and 72 (47%) have entered the maintenance phase. Sixty-one patients ≥ 70 (40%), compared to 35% of patients in overall population, prematurely discontinued both lenalidomide and rituximab, due to TEAEs (n = 26; 17%), progressive disease (n = 15; 10%), patient withdrawal (n = 12; 8%), death (n = 5; 3%), and other reasons (n = 3; 2%). Neutropenia was the only TEAE leading to discontinuation of lenalidomide in more than 2 patients (n = 10; 7%). Conclusions: Similar to findings in the overall population, R2 treatment in advanced-age patients with R/R FL and MZL resulted in encouraging efficacy, and with close attention to dose reduction there is a tolerable safety profile. Table Disclosures Lansigan: BMS Steering Committee for MAGNIFY Program: Membership on an entity's Board of Directors or advisory committees; Spectrum Pharma: Consultancy, Research Funding; BMS: Consultancy; Seattle Genetics: Consultancy. Andorsky:AstraZeneca: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI: Research Funding. Coleman:Novartis Pharmaceuticals: Research Funding; Merck Sharp & Dohme Corp.: Research Funding; Boston BIoMedical, Inc.: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Innocare: Research Funding; ARCUS Biosciences: Research Funding; AstraZeneca Pharmaceuticals, LP (Acerta Pharma BV Trials): Research Funding; AstraZeneca Pharmaceuticals, LP: Research Funding; BMS (Celgene Corporation): Research Funding; Eli Lilly and Company: Research Funding; EMD Serono Research and Development Institute Inc.: Research Funding; Genetech (F. Hoffman-LaRoche Ltd): Research Funding; Hutchinson MediPharma, LTD: Research Funding; Incyte Corporation: Research Funding; Ipsen Group: Research Funding; Karyopharma Therapeutics, Inc.: Research Funding; Klus Pharma, Inc.: Research Funding; MeiPharma, Inc.: Research Funding; Seattle Genetics: Research Funding. Yacoub:Novartis: Honoraria, Speakers Bureau; Agios: Speakers Bureau; Incyte: Speakers Bureau; Hylapharm: Current equity holder in private company; Cara therapeutics: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Dynavax: Current equity holder in publicly-traded company. Melear:AstraZeneca: Speakers Bureau; Janssen: Speakers Bureau. Fanning:Prisma Health: Current Employment; Abbvie: Consultancy; TG Therapeautics: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi Aventis: Speakers Bureau. Kolibaba:Compass Oncology: Ended employment in the past 24 months; Atara Biotech: Consultancy; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sumitomo Dainippon Pharma Oncology: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company; AbbVie: Research Funding; Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Verastem: Honoraria; Janssen: Research Funding; Novartix: Research Funding. Reynolds:IHA Hematology/Oncology Consultants: Current Employment. Nowakowski:Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; MorphoSys: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding. Gharibo:Bayer: Ended employment in the past 24 months; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ahn:BMS: Current Employment, Current equity holder in publicly-traded company. Li:BMS: Current Employment, Current equity holder in publicly-traded company. Rummel:Celgene: Consultancy, Honoraria; Janssen: Honoraria; Amgen GmbH: Honoraria; Roche: Honoraria; Novartis Pharma GmbH: Honoraria. Sharman:Bristol Meyers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; BeiGene: Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding.

Introduction Essential thrombocythemia (ET) and polycythemia vera (PV) patients suffer from various symptoms that worsen quality of life (QOL), yet serial data on symptom changes resulting from therapy are sparse in the literature. Patient questionnaires from 2 large multicenter trials (MPN-RC 111, 112) were used to assess change in symptom burden and QOL over 12 months and impact of baseline symptom burden on subsequent change in ET / PV patients on hydroxyurea (HU) or pegylated interferon alfa-2a (PEG). Methods Trials MPN-RC 111 was a single-arm, open-label, phase II trial evaluating response to PEG in high-risk ET / PV patients with HU resistance/intolerance or splanchnic vein thrombosis (SVT; NCT01259817). MPN-RC 112 was a randomized, open-label, phase III trial comparing response to PEG versus HU in cytoreductive therapy naïve high-risk ET / PV patients diagnosed < 5 years ago (NCT01258856). Measures Patients reported disease-related symptoms via the validated Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF), QOL via the European Organisation for the Research and Treatment of Cancer Core QOL Questionnaire (EORTC QLQ-C30), and (if applicable) PEG-related symptoms (flu-like symptoms, injection site irritation, blurry vision, vision change, flushing) at baseline, 3, 6, 9, and 12 months. Analysis Mixed models assessed mean changes from baseline in the MPN-SAF Total Symptom Score (TSS), MPN-SAF items, QOL, and PEG-related symptoms in MPN-RC 111, 112 PEG, and 112 HU patients. Mixed models also assessed the impact of baseline symptom burden (high [TSS ≥ 20] versus low) on subsequent change in PEG (MPN-RC 111 and 112) and HU patients. Results Patients Of the 135 enrolled MPN-RC 111 patients, 20 with SVT and 1 with no questionnaires were excluded. Of the remaining 114, 64 (56%) / 50 (44%) had ET / PV. Patients were 51% / 48% female. Median age was 65 / 64 years, and median time since diagnosis was 38 / 55 months. 31% / 22% had prior thrombosis, and 19% / 56% had splenomegaly. Of the 168 enrolled MPN-RC 112 patients (82 PEG, 86 HU), 2 with no questionnaires were excluded. Of the remaining 166, 79 (48%) / 87 (52%) had ET / PV. Patients were 50% / 33% female. Median age was 60 / 62 years, and median time since diagnosis was 3 / 3 months. 25% / 29% had prior thrombosis, and 11% / 37% had splenomegaly. Symptoms Questionnaire completion rates ranged from 90 - 99%, 87 - 100%, and 75 - 96% for on-treatment MPN-RC 111, 112 PEG, and 112 HU patients. At baseline, TSS (0 [absent] - 100 [worst imaginable]) and QOL (0 [very poor] - 100 [excellent]) means (SDs) were 19.5 (18.4) and 71.6 (20.1) for MPN-RC 111, 17.0 (13.6) and 67.9 (24.3) for MPN-RC 112 PEG, and 14.6 (11.4) and 73.8 (18.8) for MPN-RC 112 HU patients. On average, MPN-RC 111 patients had significant improvement of TSS, fatigue, abdominal pain, abdominal discomfort, dizziness, numbness, night sweats, and fever; MPN-RC 112 PEG patients had significant worsening of fever; and MPN-RC 112 HU patients had significant worsening of inactivity (no mean changes indicating improvement were observed). PEG patients had significant worsening of PEG-related symptoms. The greatest improvements occurred in the 46 (40%), 27 (33%), and 23 (28%) MPN-RC 111, 112 PEG, and 112 HU patients with high baseline symptom burden. On average, PEG patients with high baseline symptom burden had significant improvement of TSS, fatigue, early satiety, abdominal pain, abdominal discomfort, inactivity, headache, concentration, dizziness, numbness, insomnia, cough, night sweats, itching, bone pain, fever, weight loss, and QOL, while those with low baseline symptom burden had significant worsening of TSS, early satiety, headache, itching, and bone pain. On average, HU patients with high baseline symptom burden had significant improvement of TSS, early satiety, abdominal discomfort, headache, dizziness, numbness, insomnia, itching, and weight loss, while those with low baseline symptom burden had significant worsening of TSS, early satiety, abdominal discomfort, inactivity, concentration, and sexual desire/function (Figures 1 and 2). Conclusions Although no statistical comparisons were made across trials, overall improvements were seen in MPN-RC 111 but not 112. Patients with high baseline symptom burden experienced the greatest improvements in symptom burden and QOL during treatment with PEG or HU, which may explain the improvements seen in the more advanced patients in MPN-RC 111 compared to 112. Disclosures Mascarenhas: Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy; Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution). Yacoub:Dynavax: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Cara Therapeutics: Current equity holder in publicly-traded company; Hylapharm: Current equity holder in private company; Incyte: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Roche: Other: Support of parent study and funding of editorial support. Hoffman:Protagonist: Consultancy; Forbius: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Dompe: Research Funding. Silver:PharmaEssentia: Speakers Bureau. Mesa:Bristol Myers Squibb: Research Funding; Incyte: Research Funding; AbbVie: Research Funding; Samus Therapeutics: Research Funding; Genentech: Research Funding; CTI BioPharma: Research Funding; Promedior: Research Funding; Sierra Oncology: Consultancy; LaJolla Pharmaceutical Company: Consultancy; Novartis: Consultancy.

Background: Relapse is expected when treating patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL), with a shortened response associated with each relapse. Lenalidomide combined with rituximab (R2) has shown enhanced activity, with a recently reported median progression free-survival (PFS) of 39.4 months in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma, including those with FL and MZL (AUGMENT; J Clin Oncol. 2019;37:1188). Methods: MAGNIFY is a multicenter, phase IIIb trial in patients with R/R FL grades 1-3b, transformed FL (tFL), MZL, or mantle cell lymphoma (MCL; NCT01996865) in which optimal lenalidomide duration is being explored. Patients received 12 cycles of R2 (lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2 weekly in cycle 1 and then on day 1 of cycles 3, 5, 7, 9, and 11) followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 versus rituximab maintenance for 18 months. Data presented here focus on induction R2 in efficacy-evaluable MZL patients compared with the overall population of FL grades 1-3a+MZL (not including FL grade 3b, tFL, or MCL) receiving ≥ 1 treatment with baseline/post-baseline assessments. The primary end point is progression-free survival (PFS) by 1999 International Working Group criteria. Results: As of November 30, 2019, 393 patients with FL grades 1-3a and MZL enrolled; 76 (19%) had MZL. The median age of MZL patients was 68 years (range, 46-90), 68 (89%) had stage III/IV disease, and 72 (95%) had prior rituximab-containing therapy. Overall response rate was 68% with 39% CR/CRu, and median duration of response was 38.6 months (95% CI, 29.4-not reached [NR]). The median PFS was 41.2 months (95% CI, 38.4-NR). Efficacy results for MZL subtypes and the overall population (FL grades 1-3a + MZL) are shown in the table. Forty-two patients (55%) have completed 12 cycles of R2, and 41 (54%) have been randomized and entered maintenance. Twenty-eight patients (37%) prematurely discontinued both lenalidomide and rituximab, primarily due to adverse events (AEs; n = 11; 14%) and progressive disease (n = 6; 8%). The most common (≥ 20%) all-grade AEs were neutropenia (49%), diarrhea (37%), anemia (25%), thrombocytopenia (24%), and constipation (24%). Most common (≥ 10%) grade 3/4 AEs were neutropenia (41%; 1 patient [1%] had febrile neutropenia), thrombocytopenia (13%), and leukopenia (11%). Conclusions: R2 is active with a tolerable safety profile in patients with R/R MZL. The efficacy and safety profile of R2 in MZL patients were similar to results observed in the overall MAGNIFY population. Disclosures Coleman: Seattle Genetics: Research Funding; EMD Serono Research and Development Institute Inc.: Research Funding; Innocare: Research Funding; ARCUS Biosciences: Research Funding; AstraZeneca Pharmaceuticals, LP (Acerta Pharma BV Trials): Research Funding; AstraZeneca Pharmaceuticals, LP: Research Funding; BMS (Celgene Corporation): Research Funding; Eli Lilly and Company: Research Funding; Genetech (F. Hoffman-LaRoche Ltd): Research Funding; Hutchinson MediPharma, LTD: Research Funding; Ipsen Group: Research Funding; Karyopharma Therapeutics, Inc.: Research Funding; Klus Pharma, Inc.: Research Funding; MeiPharma, Inc.: Research Funding; Merck Sharp & Dohme Corp.: Research Funding; Novartis Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; Boston BIoMedical, Inc.: Research Funding; BeiGene: Research Funding; Acerta: Research Funding. Andorsky:CTI: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Research Funding. Yacoub:Roche: Other: Support of parent study and funding of editorial support; Dynavax: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Incyte: Speakers Bureau; Hylapharm: Current equity holder in private company; Cara Therapeutics: Current equity holder in publicly-traded company; Agios: Honoraria, Speakers Bureau; Novartis: Speakers Bureau. Melear:Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau. Fanning:Takeda: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; TG Therapeautics: Consultancy; Abbvie: Consultancy; Prisma Health: Current Employment; Sanofi Aventis: Speakers Bureau. Kolibaba:Atara Biotech: Consultancy; Compass Oncology: Ended employment in the past 24 months; Verastem: Honoraria; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Novartix: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Sumitomo Dainippon Pharma Oncology: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lansigan:BMS: Consultancy; Seattle Genetics: Consultancy; BMS Steering Committee for MAGNIFY Program: Membership on an entity's Board of Directors or advisory committees; Spectrum Pharma: Consultancy, Research Funding. Reynolds:IHA Hematology/Oncology Consultants: Current Employment. Nowakowski:Kymera: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Curis: Consultancy; Kite: Consultancy; MorphoSys: Consultancy, Research Funding; Denovo: Consultancy; Seattle Genetics: Consultancy; Nanostrings: Research Funding; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding. Gharibo:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Bayer: Ended employment in the past 24 months. Ahn:BMS: Current Employment, Current equity holder in publicly-traded company. Li:BMS: Current Employment, Current equity holder in publicly-traded company. Rummel:Roche: Honoraria; Amgen GmbH: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Honoraria; Novartis Pharma GmbH: Honoraria. Sharman:BeiGene: Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Abstract Background: Crown-like structures in breast adipose tissue (CLS-B), indicative of proinflammatory conditions, are most frequently observed among obese (body mass index, BMI ≥30 kg/m2) women and may contribute to poor prognosis in this group. African-American (AA) women have disproportionately higher rates of obesity than White women, and at least one prior study suggests the prevalence of CLS-B may be higher among AA women. However, most previous studies have examined CLS-B within affected tissues, which may reflect inflammation in the tumor microenvironment, and few have examined the association between CLS-B and clinical outcomes by race. Methods: We examined the presence of CLS-B detected by CD68 immunohistochemistry in normal adjacent breast tissue from a quadrant uninvolved by tumor obtained via mastectomy among 174 African-American women and 168 White women with stage I—III breast cancer diagnosed at Emory University Hospitals (2007—2012). We also investigated associations between CLS-B and other demographic and lifestyle factors at diagnosis (e.g., BMI, smoking status, age at menarche, parity, lactation, menopausal status, hormone replacement therapy use, and family history of breast cancer). Patients were followed for an average of seven years after diagnosis for recurrence and survival. Multivariable Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for associations between CLS-B presence and progression-free survival (PFS), controlling for BMI and other potential confounders. Results: Median age at diagnosis for both AA and White women was 54 years, with more than 60% postmenopausal among both groups. AA women were more likely than White women to be obese (52% vs. 24%) and have ER- tumors (30% vs. 12%). Presence of any CLS-B was similar between AA (32%) and White (29%) patients. In multivariable models, we did not find any association between CLS-B and race (HR=1.14, 95% CI: 0.72, 1.82) with the only statistically significant factors being BMI (≥30 vs. 18.5-<25 kg/m2: HR=4.36, 95% CI: 2.17, 8.76) and parity (1+ vs. 0 births: HR=0.43, 95% CI: 0.21, 0.91). Over follow-up, 46 breast cancer recurrences and 52 deaths (23 from breast cancer) occurred. Overall, the presence of CLS-B was not associated with PFS (multivariable HR: 0.97, 95% CI: 0.58, 1.62). When examined by race, there was a difference in the direction of the association between CLS-B and PFS among AA women (HR=1.25, 95% CI: 0.64, 2.46) compared to White women (HR=0.75, 95% CI: 0.33, 1.71), although this difference was not statistically significant (P=0.86). Conclusion: Our results show a strong, positive association between BMI and CLS-B in non-tumor tissue and an inverse association with parity. We did not observe a difference in CLS-B presence by race nor did we find CLS-B to be associated with worse progression-free survival, which is in contrast to previous studies that have examined the presence of CLS-B within specimens in close proximity to the tumor. Citation Format: Aswathy M Cheriyan, Mark E Sherman, Yuan Liu, Keerthi Gogineni, Jiaqi Liu, Jiabei He, Uma Krishnamurti, Ryan Ashiqueali, Jinjing He, Rami Yacoub, Jasmine Miller-Kleinhenz, Lauren E McCullough, Maret L Maliniak. Presence of crown-like structures in breast adipose tissue and clinical outcomes among African-American and White breast cancer patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C074.

8046 Background: Patients (pts) with relapsed iNHL have limited standard treatment options. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported 39.4-mo median PFS in R/R iNHL pts (AUGMENT; J Clin Oncol. 2019;37:1188). Methods: MAGNIFY is a multicenter, phase IIIb trial in pts with R/R FL gr1-3a, MZL, or MCL (NCT01996865) exploring optimal lenalidomide duration. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and then q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in pts with SD, PR, or CR to R2 vs rituximab maintenance for 18 mo. Data presented here focus on induction R2 in efficacy-evaluable FL and MZL pts (MCL not included) receiving ≥ 1 treatment with baseline/post-baseline assessments to analyze the primary end point of ORR by 1999 IWG criteria. Results: As of June 16, 2019, 393 pts (81% FL gr1-3a; 19% MZL) were enrolled with a median follow up of 23.7 mo (range, 0.6-57.8) for censored pts (n = 335). Median age was 66 y (range, 35-91), 83% had stage III/IV disease, with a median of 2 prior therapies (95% prior rituximab-containing). ORR was 69% with 40% CR/CRu (Table). Median DOR was 39.0 mo, and median PFS was 40.1 mo. 199 pts (51%) have completed 12c of R2, and 188 (48%) have been randomized and entered maintenance. 139 pts (35%) prematurely discontinued both lenalidomide and rituximab, primarily due to AEs (n = 52, 13%) or PD (n = 45, 11%). Most common all-grade AEs were 48% fatigue, 43% neutropenia, 36% diarrhea, 31% nausea, and 30% constipation. Grade 3/4 AE neutropenia was 36% (9 pts [2%] had febrile neutropenia); all other grade 3/4 AEs occurred in < 7% of pts. Conclusions: R2 is active with a tolerable safety profile in pts with R/R FL and MZL, including rituximab-refractory, double-refractory, and early relapse pts. Clinical trial information: NCT01996865 . [Table: see text]

Summary Background Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. Aim To review the effect of existing medication use on high‐resolution oesophageal manometry (HRM) in a ‘real‐world’ setting. Methods Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22‐month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. Results A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta‐agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2‐10.8). Odds ratio for anticholinergics, inhaled beta‐agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. Conclusion Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

8001 Background: Smoldering multiple myeloma (SMM) is a precursor to myeloma, wherein current standard of care is observation (obs). Data from a randomized Spanish trial (Mateos et al, NEJM 2015) suggest that lenalidomide(len)/dexamethasone improves time to developing myeloma (TTP) and overall survival (OS) for patients (pts) with high risk (HR) SMM over obs. However, pts were not screened with advanced imaging techniques, used a HR definition that is not routinely available, and combination therapy limited the ability to isolate the effect of len, and thus has not become standard of care. Methods: E3A06 is a randomized phase III intergroup trial, testing the effect of single agent len compared with obs for pts with intermediate or high risk SMM. In an initial phase II run in all pts received len to demonstrate safety. Eligibility required ≥10% PCs and abnormal serum FLC ratio (<0.26 or >1.65). The primary endpoint was progression PFS was estimated by the Kaplan-Meier method and compared using the one-sided stratified log-rank test. Results: PII enrolled 44 pts and PIII randomized 182 pts to either len (n=90) or obs (n=92) [stratified on time since SMM diagnosis ≤1y vs >1y]. Baseline characteristics were similar between the arms. 80% (PII) and 51% (PIII) are off len, primarily due to adverse events (AE) or pt withdrawal. Among the len treated pts, G3/4 non-hematologic AE occurred in 28% of PIII pts with fatigue being most common (n=5). G4 hematologic AE rate was 5.7%, primarily neutropenia (n=4). 3-year cumulative incidence of invasive SPMs was 5.2% (len) and 3.5% (obs). Overall response rate was 47.7% for the phase II study, and in phase III, 48.9% for the len arm, and 0% for the obs arm. Median follow up was 71 months (PII), and 28 months (PIII). 3-year PFS was 87% for the PII cohort. One, 2 and 3-year PFS was 98%, 93%, and 91% for len, and 89%, 76%, and 66% for the obs arm (HR 0.28, p=0.0005) favoring the len arm. No difference in QOL score was noted between arms. Conclusions: Overall, this trial represents the largest randomized trial in SMM to date. In conjunction with the Spanish data, this trial may support a change in clinical practice. Clinical trial information: NCT01169337. [Table: see text]

7059 Background: Patients with chronic myelomonocytic leukemia (CMML) have historically poor outcomes, with ~6-7 mos median OS in relapsed/refractory (r/r) setting. Splenomegaly is a poor prognostic factor and potential target in CMML. CD123 is detected on blasts, monocytes, and neoplastic microenvironmental plasmacytoid dendritic cell (pDC) infiltrates part of the CMML malignant clone (Solary, et al). Tagraxofusp, a novel CD123 targeted therapy, demonstrated high levels of activity in BPDCN, an aggressive hematologic malignancy derived from CD123-expressing pDCs, and is FDA approved in BPDCN. As such, tagraxofusp may offer a novel approach in CMML. Methods: Multicenter, 2-stage Ph1/2 enrolling patients (pts) with r/r CMML. Objectives: determine optimal dose, evaluate safety and efficacy. Stage 1 dose escalation: IV tagraxofusp (7, 9, and 12 mcg/kg/day) dosed on days 1-3 every 21 days (C1-4), 28 days (C5-7), and 42 days (C8+). Stage 2 (ongoing), pts receive optimal S1 dose (12 mcg/kg/day; no MTD). Results: 20 pts (12 CMML-1; 8 CMML-2) enrolled. 18 pts 2nd-line (2 pts in 1L), HMAs most common prior therapy. Median age 69 (43-80); 81% male. 11 (52%) had baseline splenomegaly (spleen palpable below left costal margin by physical exam) of 2-27 cm. Most common TRAEs: hypoalbuminaemia (35%), thrombocytopenia (35%), nausea (30%), vomiting (30%), and fatigue (20%). Most common ≥Gr3 TRAEs were thrombocytopenia (35%) and nausea (5%). Capillary leak syndrome in 3 pts (15%; all Gr1&2). 100% (10/10) of pts with splenomegaly had spleen response: 80% (8/10) had reductions ≥50% and 67% (4/6) with spleen size ≥5 cm had reductions ≥50%. 3 pts achieved bone marrow complete responses, including 1 pt bridged to SCT in remission. Conclusions: Tagraxofusp demonstrated single agent activity in CMML as 80% of pts showed ≥50% reduction in splenomegaly by palpation. Splenomegaly in CMML, as in myelofibrosis, is a major cause of morbidity and associated with poor prognosis and impaired QoL. Targeting splenomegaly in myeloid neoplasms with proliferative features may be an important therapeutic goal. Given CD123 expression on CMML blasts, monocytes, and malignant pDCs, tagraxofusp may offer a targeted approach, especially in pts with splenomegaly. Updated safety and efficacy data to be presented. Registrational trial planned. Clinical trial information: NCT02268253.

7058 Background: Patients with myelofibrosis (MF) who fail or are intolerant to JAK inhibitors (JAKi) have no standard treatment options. CD123 is expressed on a variety of malignancies, including MF. CD123+ plasmacytoid dendritic cells (pDCs), in the MPN microenvironment, including chronic myelomonocytic leukemia and MF, may be tumor-promoting. Monocytosis in MF associated with rapid disease progression and short survival, suggesting an accelerated disease phase. Notably, monocytes share a common precursor with CD123+ pDCs. Tagraxofusp, a novel CD123 targeted therapy, demonstrated high activity in patients with BPDCN, an aggressive hematologic malignancy derived from CD123+ pDCs, and is FDA approved in BPDCN. As such, tagraxofusp may offer a novel therapeutic approach in MF. Methods: Multicenter, 2-stage Ph 1/2 trial enrolling patients (pts) with MF relapsed, refractory, or intolerant to JAKi. Objectives: determine optimal dose, evaluate safety and efficacy. Stage 1 dose escalation: IV tagraxofusp (7, 9, and 12 mcg/kg/day) dosed daily days 1-3 every 21 days (C1-4), 28 days (C5-7), and 42 days (C8+). Stage 2 (ongoing): pts receive optimal S1 dose (12 mcg/kg/day; no MTD). Results: 23 r/r pts treated. Median age 69 (55-81); 57% female. DIPSS Plus: 4% INT-1, 55% INT-2, 41% high. Baseline platelets: median 59 K/uL (15-579); 70% (16/23) <100 K/uL, 8 pts <50 K/uL. 87% (20/23) baseline splenomegaly (palpable ≥5 cm below left costal margin by physical exam). Most common TRAEs: headache (22%), hypoalbuminaemia (22%), ALT incr. (17%) and thrombocytopenia (17%). Most common ≥Gr3 TRAE thrombocytopenia (2%). Capillary leak syndrome in 1 pt (4%; Gr3). 57% (8/14) of pts with baseline spleen ≥5cm BCM spleen responses: 43% (6/14) had ≥29% and 21% (3/14) had ≥45% reduction. 100% of pts with baseline spleen ≥5cm and monocytosis splenomegaly reductions: 80% (4/5) had ≥29% and 40% (2/5) had ≥45%. 6 pts (3 monocytosis pts and 5 pts platelets <100 K/uL) had 6 mos+ duration, 9 pts ongoing. Conclusions: Tagraxofusp demonstrated single agent activity (reduction in splenomegaly) and manageable safety in R/R MF, including pts with monocytosis, an unmet medical need. Given the presence of CD123+ pDCs, tagraxofusp may offer a novel targeted approach in MF. Updated data to be presented. Registrational designs are being evaluated. Clinical trial information: NCT02268253.

Background Patients with myelofibrosis (MF) who fail or are intolerant to JAK inhibitors (JAKi) have limited treatment options. Tagraxofusp is a targeted therapy directed to CD123 that was approved by the FDA for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). CD123 is expressed on a variety of malignancies including BPDCN, acute myeloid leukemia (AML), and certain myeloproliferative neoplasms (MPN), including MF. High-expressing CD123+ plasmacytoid dendritic cells (pDCs), the cell of origin of BPDCN, have been detected in the microenvironment of certain myeloid neoplasms, including MF, where they may play a tumor-promoting role. Notably, pDCs share a common precursor cell with monocytes, and monocytosis has been reported as a poor prognostic factor in patients with MF, associated with shortened overall survival. We hypothesized that tagraxofusp may offer a novel and rational therapeutic approach in patients with relapsed/refractory MF, and in particular in patients with monocytosis. Aims To assess safety and evaluate efficacy of tagraxofusp in patients with MF who were relapsed, refractory, or unable to tolerate JAKi. Methods This multicenter, open-label Phase 1/2 trial is enrolling patients with MF. In the Stage 1 (dose escalation), tagraxofusp was administered as a daily IV infusion at 7, 9, or 12 mcg/kg on days 1-3 every 21 days (cycle 1-4), 28 days (cycles 5-7), and 42 days (cycles 8+). In Stage 2 (expansion), patients are receiving the recommended Phase 2 dose (12 mcg/kg). Results 27 patients with MF have been treated, including 14 patients who had previously received ≥ 3 lines of therapy. Median age was 69 years (range 54-81), 52% were female, and 26% had baseline monocytosis (≥ 1x109/L). Baseline risk assessment based on the DIPSS Plus risk group assessment showed 1 patient (4%) with intermediate-1, 16 patients (59%) with intermediate-2, and 9 patients (33%) with high-risk. At study entry, median platelet count was 59 K/uL; 67% of patients had baseline platelets &lt;100 K/uL, of which 10 patients had platelets &lt;50 K/uL. 74% of patients had baseline splenomegaly (spleen palpable ≥ 5 cm below the left costal margin). In terms of molecular mutations: JAK2 (n=18); CALR (n=3); and MPL (n=1), and additional molecular analysis showed ASXL1 (n=5). In terms of cytogenetics, 30% (8/27) of patients had an abnormal karyotype, mainly 20q- (n=3), -5/5q-, -7/7q-, and 12p- (each n=2). Most common treatment-related adverse events (TRAEs, incidence ≥ 15%) include headache, hypoalbuminemia, increased levels of alanine aminotransferase, thrombocytopenia, and anemia. Most common ≥ grade 3 TRAE's were thrombocytopenia (8%) and anemia (15%). Capillary leak syndrome was reported in 1 patient (grade 3). Among the 17 evaluable patients with baseline splenomegaly, 53% had spleen size reductions, of which 4 patients had reductions of &gt; 45%. In 5 patients with baseline splenomegaly and monocytosis (&gt;1x109/L monocytes), 80% (4/5) had spleen size reductions, of which 2 had reductions of &gt;45%. Five patients had treatment duration of 12 months or more, with two of those patients ongoing (13+,and 24+ months, respectively). Six patients with platelets &lt;100 K/uL had treatment duration of 6 months or more, including 3 patients with baseline monocytosis who had treatment duration of 12 months or more. 7 patients had objective responses (IWG-MRT 2013 responses), including Clinical improvement (CI) (n=5) and CI (Symptom) (n=2). 20 patients were evaluable for symptomatic assessment (MPN-SAF TSS). Symptom response rate was 45% (defined as ³50% reduction in TSS score). Reductions in both symptom score and spleen size was noted in 6/6 patients who had splenomegaly at baseline. Conclusions Tagraxofusp demonstrated single agent clinical activity, with a predictable and manageable safety profile, in patients with relapsed/refractory MF, including in patients with monocytosis, a poor prognostic factor and unmet medical need. Tagraxofusp may offer MF patients, and MF patients with monocytosis in particular, a novel treatment option. Enrollment continues, and updated trial data will be presented. This clinical trial is registered at clinicaltrials.gov: NCT02268253. Disclosures Pemmaraju: affymetrix: Research Funding; sagerstrong: Research Funding; Daiichi-Sankyo: Research Funding; plexxikon: Research Funding; novartis: Consultancy, Research Funding; Stemline Therapeutics: Consultancy, Honoraria, Research Funding; cellectis: Research Funding; celgene: Consultancy, Honoraria; samus: Research Funding; mustangbio: Consultancy, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; incyte: Consultancy, Research Funding. Gupta:Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Research Funding. Yacoub:Dynavax: Equity Ownership; Cara: Equity Ownership; Ardelyx: Equity Ownership; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Agios: Speakers Bureau; Hylapharm: Equity Ownership. Wang:Agios: Other: Advisory role; Amgen: Other: Advisory role; Daiichi: Other: Advisory role; Stemline: Other: Advisory role, Speakers Bureau; Pfizer: Other: Advisory role, Speakers Bureau; celyad: Other: Advisory role; Abbvie: Other: Advisory role; Kite: Other: Advisory role; Jazz: Other: Advisory role; Astellas: Other: Advisory role, Speakers Bureau. Lee:AstraZeneca Pharmaceuticals: Consultancy; Ai Therapeutics: Research Funding; Karyopharm Therapeutics: Consultancy; Roche Molecular Systems: Consultancy; Jazz Pharmaceuticals, Inc: Consultancy; Helsinn: Consultancy. Schiller:Agios: Research Funding, Speakers Bureau; Karyopharm: Research Funding; Onconova: Research Funding; Novartis: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; Amgen: Other, Research Funding; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding; Bristol Myer Squibb: Research Funding; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding. Sardone:Stemline Therapeutics: Employment, Equity Ownership. Wysowskyj:Stemline Therapeutics: Employment, Equity Ownership. Chen:Stemline Therapeutics: Employment, Equity Ownership. Brooks:Stemline Therapeutics: Employment, Equity Ownership, Patents & Royalties. Poradosu:Stemline Therapeutics: Employment, Equity Ownership, Patents & Royalties. McDonald:Stemline Therapeutics: Employment, Equity Ownership. Rupprecht:Stemline Therapeutics: Employment, Equity Ownership. Talpaz:Imago BioSciences: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CTI BioPharma: Research Funding; Constellation: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Samus Therapeutics: Research Funding. Taparia:Novartis: Consultancy. Verstovsek:Protaganist Therapeutics: Research Funding; Ital Pharma: Research Funding; Astrazeneca: Research Funding; Pharma Essentia: Research Funding; Sierra Oncology: Research Funding; Novartis: Consultancy, Research Funding; Blueprint Medicines Corp: Research Funding; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. Khoury:Kiromic: Research Funding; Angle: Research Funding; Stemline Therapeutics: Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.