ALBERT

Description: Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor’s molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment.

Description: Plastic waste can promote microbial colonization by pathogens implicated in outbreaks of disease in the ocean. We assessed the influence of plastic waste on disease risk in 124,000 reef-building corals from 159 reefs in the Asia-Pacific region. The likelihood of disease increases from 4% to 89% when corals are in contact with plastic. Structurally complex corals are eight times more likely to be affected by plastic, suggesting that microhabitats for reef-associated organisms and valuable fisheries will be disproportionately affected. Plastic levels on coral reefs correspond to estimates of terrestrial mismanaged plastic waste entering the ocean. We estimate that 11.1 billion plastic items are entangled on coral reefs across the Asia-Pacific and project this number to increase 40% by 2025. Plastic waste management is critical for reducing diseases that threaten ecosystem health and human livelihoods.

Description: 〈p〉What is universal about music, and what varies? We built a corpus of ethnographic text on musical behavior from a representative sample of the world’s societies, as well as a discography of audio recordings. The ethnographic corpus reveals that music (including songs with words) appears in every society observed; that music varies along three dimensions (formality, arousal, religiosity), more within societies than across them; and that music is associated with certain behavioral contexts such as infant care, healing, dance, and love. The discography—analyzed through machine summaries, amateur and expert listener ratings, and manual transcriptions—reveals that acoustic features of songs predict their primary behavioral context; that tonality is widespread, perhaps universal; that music varies in rhythmic and melodic complexity; and that elements of melodies and rhythms found worldwide follow power laws.〈/p〉

Description: Background : Treatment for relapsed multiple myeloma (MM) has evolved with the availability of many novel agents; outcomes in patients with newly diagnosed MM have improved with IMiD® agents (lenalidomide [R] or pomalidomide) and proteasome inhibitor (PI) use. Regardless of autologous stem cell transplant, many patients receive R maintenance therapy (Jagannath, Blood Adv 2018; Palumbo, N Engl J Med 2012). However, there is a lack of data describing the nature of relapse and treatment choices for patients progressing on R maintenance therapy. Recent phase III data do not evaluate these patients who are relapsed or refractory to R; current treatment guidelines do not specifically recommend second-line (2L) treatment options for these patients (Laubach, Leukemia 2016). However, phase III data show that pomalidomide in combination with bortezomib and dexamethasone improves progression-free survival (PFS) (HR 0.54; P = 0.0027) in R-exposed and refractory patients, including those with 1 prior line (Richardson, J Clin Oncol 2018). The Connect MM Registry is a US, multicenter, prospective observational cohort study designed to examine diagnostic and treatment patterns, clinical outcomes and quality of life in patients with MM. For patients who received R maintenance therapy, we describe patterns of relapse, 2L treatment choice, and outcomes. Methods : From 250 sites, transplant eligible and ineligible adult patients ≤ 60 days from MM diagnosis were enrolled (N = 3011). Patients were treated at physicians' discretion and followed up for treatment and outcomes until early discontinuation or study end. Patients who relapsed during R maintenance therapy (≤ 15 mg; assessed by treating physician), were analyzed for baseline (BL) characteristics, nature of relapse, and 2L treatment. Patients with symptoms at time of relapse were defined as the presence of ≥ 1 CRAB (hyperCalcemia, Renal failure, Anemia, and Bone disease) criterion ± 60 d from PD; absence of CRAB criteria at PD in this window was considered nonsymptomatic relapse. Primary endpoint was PFS from start of 2L; safety (serious adverse events; SAE) from start of 2L was also assessed. Logistic regression analyses on all BL factors and factors before start of 2L treatment were performed to determine covariates differentiating comparator groups. Survival outcomes were analyzed using a Cox regression after adjusting for covariates. Results : Data cutoff: 1/15/18. Of 2938 treated patients, 1102 entered 2L, 236 having received R maintenance therapy in 1L. Of those patients, 52% (n = 123) and 47% (n = 112) experienced symptoms at time of relapse and nonsymptomatic relapse, respectively (data not available for 1 patient). The top ten 2L regimens are presented in the Table. Median duration of prior maintenance therapy (367 d [IQR: 577] vs 489 d [IQR: 599]) and time from first progression to start of 2L treatment (0.3 vs 0.3 mo) did not notably differ between nature of relapse groups. Prolonged median PFS from start of 2L was observed for patients receiving triplet+ (≥ 3 agents) vs doublet (≤ 2 agents) regimens (HR: 0.72; Figure 1). PFS was better for IMiD agent + PI group compared with PI (without IMiD agents) group (HR, 0.68; Figure 2). Results of sensitivity analyses and overall survival will be presented. SAEs occurred similarly among treatment groups: 42.6% with IMiD agent + PI, 34.5% with IMiD agent (without PI), and 35.8% with PI. Conclusions: This is the first description of relapse patterns, 2L treatment choice and survival outcomes after PD on R maintenance therapy in community-based patients. Nearly equal numbers of patients had symptoms at time of relapse and nonsymptomatic relapse on R maintenance therapy. After PD on R maintenance, approximately 50% of patients switched to PI regimens without IMiD agents, 25% continued with IMiD agent + PI regimens, and 25% continued in the IMiD agents group. Our data show PFS benefit for triplet+ over doublet treatment in 2L. Patients in the IMiD agent + PI group gained survival benefits over patients in the PI group. Further characterization of the patients continuing with IMiD treatment in 2L after R maintenance therapy relapse (~ 25% of patients) are ongoing. Follow-up with recently approved agents (elotuzumab, daratumumab) and their use in 2L is limited in this analysis. These data may be used to better inform treatment choices after relapse on R maintenance therapy. Disclosures Jagannath: Celgene: Consultancy; Merck: Consultancy; Multiple Myeloma Research Foundation: Speakers Bureau; Medicom: Speakers Bureau; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. Narang:Janssen: Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Ailawadhi:Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy. Rifkin:Celgene: Consultancy; Boehringer Ingelheim: Consultancy; McKesson: Equity Ownership; EMD Serono: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Sandoz: Consultancy. Terebelo:Celgene: Consultancy; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Pharmacyclics: Speakers Bureau. Toomey:Celgene: Consultancy; Myriad Genetics: Speakers Bureau; Dava Oncology: Other: Travel. Durie:Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Hardin:Celgene: Consultancy. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel; Takeda: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel, Research Funding. Wagner:EveryFit: Consultancy; Gilead: Consultancy; Janssen: Consultancy. Omel:Takeda 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. Srinivasan:Celgene: Employment. Kitali:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:Prothena: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Description: Introduction: Lenalidomide (LD) is an oral thalidomide analog with both immunomodulatory and anti-angiogenic properties. It is approved for use in myelodysplastic syndromes (MDS), specifically low-risk and intermediate 1 with 5Q-. LD has also been approved for relapsed multiple myeloma (MM). A major complication associated with LD includes venous thromboembolism (VTE), especially in combination with steroid and erythropoetin (EPO). VTE occurs in 2% of MDS, but range from 6.6% as monotherapy in MM to 8.5%–13.5% when combined with dexamethasone. Zonder reports a preliminary incidence of 75% (9/12 patients) in the SWOG 0302 trial of LD and dexamethasone in previously untreated myeloma. With the addition of ASA in these patients the incidence dropped to 19%. Patients with polycythemia rubra vera (PRV) have a higher incidence of VTE (5.1%〉 age 70). JAK-2 mutation (tyrosine kinase mutation) occurs as a sporadic event in 75% of patients with PRV and is associated with an older age group, inferior survival, myelofibrosis, acute leukemia and thromboembolic events. Recent studies with LD in this group of PRV and spent-phase myelofibrosis have shown encouraging results. LD has an activity of 46% in myelofibosis by decreasing transfusions and splenomegaly. It would seem to have activity in spent-phase PRV. We report a seminal event of splenic infarction in a patient with PRV and myelofibrosis treated with LD. Case Presentation: A 73 y/o male was diagnosed with PRV 16 yrs earlier. He underwent phlebotomy and received ASA. With a hyperproliferative phase he received hydrea as he was intolerant of IFN-A and anagrelide. Three months earlier, he developed fever, sweats, splenomegaly, and became transfusion dependent. His marrow confirmed myelofibrosis with dysplastic features. LD was begun at 25 mg daily. Three weeks later he developed pneumonia with bronchospasm and required hospitalization for antibiotics and steroids. He improved but returned 4 days later with left upper quadrant pain with CT findings consistent with multiple splenic infarcts. Prednisone was stopped and enoxaparin resulted in marked improvement. Currently, he has marked diminution in the size of his spleen from 13 cm to 4 cm. Currently, he is transfusion independent with marked clinical improvement. Discussion: This report points several dynamic issues within the field of myeloproliferative syndromes. The JAK-2 mutation offers fertile areas of research within MPD disorders as a causative or sporadic mutation and as an associated with several adverse events including VTE and myelofibrosis. We report here a unique occurrence of VTE in the form of multiple splenic infarctions within the context of treatment of the spent-phase of PVR with JAK-2 mutation receiving LD. VTE events associated with LD are associated with DVT or pulmonary embolus and have not been associated with splenic infarction. Splenic infarction has also been reported in myelofibrosis. As further studies confirm efficacy with myelofibrosis it should be suggested that prophylaxis with warfarin or enoxaparin, especially in JAK-2 mutation patients, be considered. Physicians should be encouraged to report their experience in patients with MPD and lenalidomide.

Description: Introduction: Between 2009 and 2015, use of novel therapies (immunomodulating drugs and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time frame may help project near-term future treatment patterns. Connect® MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed MM (NDMM). Pts with NDMM were enrolled in 2 sequential cohorts from Sep 2009 to Apr 2016. This noninterventional registry did not prescribe or limit therapy choices. Study sites represented all census regions, with 89% and 11% split between community and academic sites, respectively. This allowed a reasonable generalizability to patterns for the US. Methods: Connect® MM enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493 NDMM pts from Sep 2009 to Dec 2011, and Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at a baseline visit and quarterly visits thereafter until death or discontinuation. The current analysis was conducted for the population of treated pts (N=2848) as of May 2016. This study examined recorded treatment choice of first-line regimen, maintenance therapy, and second-line regimen in 6-month intervals. Trends in regimens were graphically represented using "Tepee" plots (Srinivasan, Shankar. Resource Tepee. Patent US 7,495,673 B1. 24 Feb 2009). Briefly, all pts who initiated treatment during each 6-month interval are represented horizontally, with each horizontal line indicating 100% of all treatment used in that period. The regimens are represented by gray shading with wider bands signifying the more frequently used regimens at each time interval. Results: Median follow‐up for all pts was 39.3 months (0.03‐78.4) in Cohort 1 and 15.4 months (0.2-40.1) in Cohort 2. For the treated population, the median age was 67 years (range 24‐94), 58% were male, 83% were white, and 38% of those reporting International Staging System stage had stage III MM. By US geographical region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 80.2%) were from community sites, and 397 (13.9%) were from academic sites with the remaining from government sites. A total of 1416 (47.4%) reported an intent to transplant (stem cell transplant [SCT]) at the initiation of therapy. A total of 666 (25.8%) have progressed and entered second line. Tepee plots of treatment patterns for start of induction for those pts with and without SCT intent are provided in Figure 1A and 1B, respectively. The year 2012 does not feature in these induction plots, as this period corresponds to a time when pts were not enrolled-Cohort 1 had been completed and Cohort 2 had not yet opened. The 4 most common induction regimens for SCT intent, from left to right, in order of decreasing frequency of use, were lenalidomide (R), bortezomib (V), dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 5 most common induction regimens for those without SCT intent, from left to right, in order of decreasing frequency of use, were VD, RD, RVD, CyBorD, and V. Triplet therapy in first-line induction pts increased in frequency from 2009 to 2014. The 4 most frequent maintenance regimens for those with SCT intent were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for pts who did not intend to receive SCT were R monotherapy, RD, VD, and V monotherapy. The most prevalent regimens in the second line were VD, RD, V, and RVD. Additional graphs including treatment patterns by age group (≤ 70 vs 〉 70 years) and maintenance by conduct of first-line SCT will be presented. Conclusions: Our work utilizes Tepee plots to outline induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional registry study in the US. Triplet therapy use increased in the time period studied, with RVD being the most frequently used triplet for pts with or without SCT intent. The most common maintenance regimens included R as monotherapy or in combination. Disclosures Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen/ONYX: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Gasparetto:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria. Jagannath:Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Terebelo:Celgene: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene: Consultancy. Kitali:Celgene: Employment, Equity Ownership. Zafar:Celgene: Employment. Srinivasan:Celgene: Employment; Individual Patent: Patents & Royalties: US7,495,673B1 Used for MM-Connect Treatment Patterns Abstract.. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Description: Background: Increased rates of SPM have been observed as newer cancer treatments have improved survival over the past 2 decades (Fraumeni et al. NCI, 2006). Higher incidence of specific types of hematologic SPM following MM, especially acute myeloid leukemia and myelodysplastic syndromes, have been reported relative to the general population (Dores et al. NCI, 2006; Mailankody et al. Blood, 2011; Ravazi et al. Blood, 2011; Landgren and Mailankody. Leukemia, 2014). A complex interplay between myeloma-, host-, environmental-, and treatment-related factors likely contributes to the increased incidence of SPM in MM. Connect MM is the first and largest prospective, observational, US-based, multicenter registry designed to characterize patients (pts), treatment patterns, and outcomes in newly diagnosed MM (NDMM) pts. Methods: Between September 2009 and November 2012,a total of 1493 NDMM pts were enrolled from 234 US sites within 2 mos of the first diagnosis of MM. Patient data were collected at baseline and each subsequent quarter using a standardized form. Invasive SPM included hematologic and solid tumor second cancers and non-invasive SPM were defined as non-melanoma skin cancers (NMSC). SPM incidence and incidence rate (IR; number of pts with SPM per 100 patient-yrs [PY]) were calculated for all pts and by exposure to specific treatments, including lenalidomide (LEN). PYs were calculated as the observation period from the start of treatment until the detection of the first reported SPM (per category), death, or end of follow-up (pt lost or data cutoff). Results: As of Dec 10, 2013, SPM data were available for 1493 NDMM pts. The median age was 67 yrs (range, 24-94 yrs), 82% of patients were white and 57% were male. Median follow-up was 29.0 mos (0-49 mos). The median OS of treated pts was 44.4 mos. Fifty pts did not receive treatment and had no SPM reported. A total of 74 of the 1443 treated pts (5.1%) reported SPM. Invasive SPM were observed in 51 pts (3.5%): 37 pts (2.6%) with solid tumors and 14 pts (1.0%) with hematologic SPM. Lung/bronchus and myelodysplastic syndromes were the most frequently reported solid tumor and hematologic SPM respectively. NMSC were reported for 26 pts (1.8%). 3 pts had both an invasive SPM and NMSC. The IRs for invasive, hematologic, and solid tumor SPM by LEN exposure are listed in Table 1. By multivariate analysis, the only significant risk factor for the occurrence of SPM was prior history of invasive malignancy. Demographics (including age, ethnicity, race, and gender), International Staging System stage, family history of myeloma or other cancers, history of smoldering MM or monoclonal gammopathy of unknown significance, or prior radiation therapy were not associated with the occurrence of SPM. Conclusions: This analysis shows that there was no increased risk of invasive SPM in this disease-specific registry of pts with NDMM. The risk of SPM for LEN exposed pts was not greater than that for pts not exposed to LEN. In addition, multivariate analysis indicated the only significant risk factor for SPM was prior history of invasive malignancy. As additional agents are approved for the treatment of MM and the length of pt survival increases, longer prospective observation with expanded enrollment on the registry will better characterize the occurrence of SPM in this pt population. Correlations with risk factors including age, pre-existing MDS, risk status, as well as type and duration of therapy will continue to be investigated. Table 1. Incidence rates (per 100 PYa) by treatment exposure IR per 100 PY (95% CI) SPM LEN-Exposed (n = 977) Non–LEN Exposed (n = 466) Invasive 0.85 (0.61-1.19) 1.16 (0.72-1.86) Hematologic 0.17 (0.08-0.36) 0.47 (0.22-0.99) Solid tumor 0.67 (0.46-0.98) 0.68 (0.36-1.26) NMSC 0.50 (0.32-0.77) 0.41 (0.18-0.91) a PY of exposure is the sum of exposure of all pts. Disclosures Rifkin: Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Shah:Celgene Corp: Consultancy, Research Funding. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Lu:Celgene Corp: Employment. Kenvin:Celgene Corp: Employment. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Durie:Celgene Corp: Expert Board Committee Other; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees; IRC J&J: Membership on an entity's Board of Directors or advisory committees.

Description: Contrary to the traditional concept, in many instances the leukemias are characterized by an essentially normal or slower individual leukocyte generation time, impaired maturation, altered cell release into the circulation, and prolonged survival of the "leukemic" cell, resulting in a progressive accretion of the potentially divisible cell population arrested in intermediary phases of development. We have come to a critical reorientation in our thinking of the leukemias and neoplasia in general. Continued expansion along conventional lines might be profitably complemented by another program aimed at correction of the leukemic process by encouraging maturation without cellular destruction. The significance of this moment is the inevitable realization that the dream of a cell specific "magic bullet" which would jam the metabolic machinery of the "leukemic cell" may instead correct that defective mechanism by aiding the leukocyte to mature properly. Efforts to accelerate or correct the altered maturation may offer additional approaches to the treatment of the leukemias with or without conventional chemotherapy. A reevaluation of the leukemias and possibly other neoplasms as disorders primarily of accumulation rather than proliferation may be a useful working hypothesis to encourage newer therapeutic approaches.

Description: AMG 531 is a novel platelet-stimulating peptibody that stimulates the thrombopoietin (TPO) receptor, and is being studied for its ability to increase production of platelets. We report safety data in both S and NS patients (pts) from 2 randomized, double blind, placebo-controlled Phase 3 studies designed to evaluate the efficacy and safety of AMG 531 in adult pts with chronic ITP. All pts that received at least 1 dose of AMG 531 were counted as AMG 531-treated pts in this safety analysis. Of the 125 pts enrolled, 63 were S (placebo, 21; AMG 531, 42), and 62 were NS (placebo, 21; AMG 531, 41) with a median age of 52 years (range 21 to 88) and a mean baseline platelet count of 16.5x109/L. Subcutaneous AMG 531 or placebo was administered weekly for 24 weeks at a starting dose of 1μg/kg, and adjusted to maintain a target platelet count of 50–200x109/L. Among AMG 531 pts, the mean weekly dose was 3.3±2.7 μg/kg, with most pts (54/84, 64%) receiving a dose between 1 and 4μg/kg. There was no difference in the safety profile between S and NS pts treated with AMG 531; therefore safety data were pooled. Adverse events were reported in 39/41 (95%) placebo and in all (100%) AMG 531 pts. The most frequently reported adverse events (AEs) were: headache (placebo vs AMG 531; 32% vs 35%), fatigue (29% vs 33%), epistaxis (24% vs 32%), arthralgia (20% vs 26%), and contusion (24% vs 25%). There were 2 AMG 531-related serious AEs, both in S pts; 1 pt with elevated bone marrow reticulin after 4 weeks of receiving AMG 531 that returned to baseline 3 months after drug withdrawal, and 1 pt experienced thrombosis (right transfemoral popliteal embolectomy) that was successfully treated allowing study continuation. One (2.4%) placebo and 3 (3.6%) AMG 531 pts withdrew from the study due to AEs. Three placebo pts died of cerebral hemorrhage, atypical pneumonia, and pulmonary embolism. One AMG 531 pt died of intracranial hemorrhage 2 weeks after discontinuation of AMG 531. The total number of bleeding events in the 42 placebo pts and 83 AMG 531 pts were 76 and 152, respectively, corresponding to an exposure-adjusted incidence of 7.9 and 7.8 per 100 Patient-Weeks, reduced to 5.2 per 100 Patient-Weeks in AMG 531-treated pts when their platelet counts were ≥50x109/L (platelet response). Clinically significant bleeding events (MedDRA 9.0 defined severity grade ≥3) did not occur in responding pts, and were reported only when platelet counts were

Description: As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.