Citations

Abstract BACKGROUND: Symptom burden in essential thrombocythemia (ET) and polycythemia vera (PV) is severe even among individuals with low risk disease (Blood 2012. 12;123(24):3803-10). New therapies exist which alleviate the severe symptom burden and reduce splenomegaly in ET and PV patients (N Engl J Med 2015; 372:426-435). This analysis is the first to date to evaluate thresholds at which symptom-based treatment can be considered for ET and PV patients who are intolerant or resistant to hydroxyurea (HU). METHODS: Patient demographics, symptom burden, and disease traits were collected from ET and PV patients at a single time point during therapy. The MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103) was utilized to assess symptom burden. Symptom criteria models were determined as previously described among a population of MF patients (Scherber et. al. EHA 2016: a2250). Cutoffs were then evaluated in a cohort of ET and PV patients to assess for utility as a symptom model among this population. RESULTS: Demographics and symptom burden: 838 PV and 867 ET patients with previous hydroxyurea therapy were included in this analysis. Patients were of mean age (54.9 years ET, 64.0 years PV) and gender (69.2% female ET, 55.7% female). Mean disease duration was 6.0 years for ET and 7.3 years for PV.Among ET and PV patients, 15.0% and 24.2% had prior thrombosis respectively. In evaluating prognostic risk, ET patients tended to be low (45.5%) or intermediate risk (42.9%) with only a minority of patient meeting criteria forhigh risk disease (11.6%). Laboratory findings: ET patients had a mean platelet value of 598.7x 109/L(SD=283.4). Among PV patients, mean hematocrit was 45.8% (SD=8.1) and 42.6% of patients had a hematocrit of greater than 45%. White blood cell count was normal between the two groups (ET mean 8.3 x 109/L, PV mean 9.0 x 109/L). Symptoms: Mean worst symptom severity was 6.4 out of 10 (SD=2.7). Among ET patients, worst symptom was most frequently fatigue (32.7%, mean 5.0/10, SD=3.1, overall prevalence 88%) followed by night sweats (13.6%, mean 2.0/10, SD=3.0, overall prevalence 53%) and concentration difficulties (8.6%, mean 3.1/10, SD=3.0, overall prevalence 68%). For PV, worst individual symptom items were most frequently fatigue (29.2%, mean 5.2/10, SD=3.0, overall prevalence 91%), pruritus (14.1%, mean 3.2/10, SD=3.2, overall prevalence 69%), and night sweats (12.8%, mean 2.5/10, SD=3.0, overall prevalence 57%). Cutoff Scoring: 47.0% of ET patients fit criteria for TSSgreater than to equal to 20; 59.0%% had a single itemgreater than 5; and 45.7% had both a TSS greater than or equal to 20 and a single item greater than 5. Among PV participants, 54.5% had aTSS greater than to equal to 20; 66.1% had a single itemgreater than 5; and 51.5% had both a TSS greater than or equal to 20 and a single item greater than 5. Each scoring method was significantly associated with individual item scores (Table 1). Prognostic scoring was not significantly associated with any of the symptom cutoffs evaluated. Correlations: Among ET patients, a prior history of thrombosis was significantly associated with having a worst symptom item greater than 5 (p=0.043). ET patients with lower hemoglobin were significantly more likely to meet criteria for a MPN-10 score greater than or equal to 20 or to meet combined criteria for a MPN-10 greater than or equal to 20 and single worst item greater than 5 (for both p=0.01 or less). For PV, lower hematocrit levels were significantly associated with having an individual worst symptom score of greater than 5 (44.9% versus 46.7%, p=0.0376). CONCLUSION: Assessment of ET and PV symptoms, now measurable through standardized and practical instruments such as the MPN-10, is an integral part of determining therapeutic impact of newer therapies in both clinical practice and trial settings. In our modeling, patients with severe symptom burden profiles are well represented by utilizing cutoff criteria including aworst individual symptom item of greater than 5 out of 10, an MPN-10 score of greater than or equal to 20, or combined criteria of both cutoffs. These cutoffs can be considered when determiningwhich HU intolerant or resistant patients would most benefit fromsymptom orientedtreatment. Disclosures Kiladjian: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding. Schouten:Novartis: Consultancy; Sanofi: Consultancy. Etienne:BMS: Speakers Bureau; ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Pfizer: Honoraria; Novartis: Honoraria. Cervantes:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

Abstract Background: In the pivotal FIRST trial, at the pre-specified planned analysis for progression-free survival (PFS), treatment (Tx) with lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) improved outcomes for transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM) compared with melphalan, prednisone, and thalidomide (MPT), as well as Rd for 18 cycles (Rd18; Benboubker, NEJM 2014). Rd18 was added as a third arm to investigate whether Rd continuous Tx would control progression of NDMM longer than Rd18. Here, we present the final analysis of the overall survival (OS) data from the trial. Methods: Transplant-ineligible pts with NDMM were randomized 1:1:1 to Rd continuous (with lenalidomide given on days 1-21 of 28-day cycles until disease progression), Rd18 (with lenalidomide given on days 1-21 of eighteen 28-day cycles), or MPT (twelve 42-day cycles); both Rd18 and MPT were 72 weeks in duration. The primary endpoint was PFS and the key secondary endpoint was OS; the primary comparison was Rd continuous vs MPT. Other secondary endpoints included time to second therapy (TTST) and safety. Time from randomization to second progression or death (PFS2) was an exploratory analysis. Response assessment used for PFS and PFS2 analysis was determined by investigators based on International Myeloma Working Group criteria. Results: At the time of cutoff for the final OS analysis (January 21, 2016), 52 of the 535 pts in the Rd continuous arm and none of the pts in the Rd18 (n = 541) and MPT (n = 547) arms continued to receive Tx. The median follow-up for surviving pts was 67.0 months (range, 0-86.8 months). In the pre-specified final OS analysis for the primary comparison, a statistically significant advantage in OS was shown with Rd continuous over MPT (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.92; P = .00234; Table). OS for Rd continuous vs Rd18 was evaluated (HR, 1.02; 95% CI, 0.86-1.20). In this updated analysis, a PFS advantage continued to be seen for Rd continuous vs MPT (HR, 0.69; 95% CI, 0.59-0.79; P < .00001) and vs Rd18 (HR, 0.70; 95% CI, 0.60-0.81). Median TTST was longer for Rd continuous vs MPT (HR, 0.63; 95% CI, 0.54-0.73; Table). More pts in the Rd18 and MPT arms started second-line therapy (n = 377 and 381, respectively) compared with the Rd continuous arm (n = 299). Pts received a variety of Tx at progression, with bortezomib-based regimens the most common in the Rd continuous (n = 179; 59.9%), Rd18 (n = 208; 55.2%), and MPT (n = 170; 44.6%) arms. Pts who received bortezomib after Rd continuous or Rd18 had better outcomes than those who received it after MPT. PFS2 for Rd continuous was improved vs MPT (HR, 0.74; 95% CI, 0.64-0.85). Grade 3/4 adverse events (AEs) occurred in 86.3%, 80.2%, and 88.7% of the 532, 540, and 541 pts in the safety populations of the Rd continuous, Rd18, and MPT arms, respectively; the most common grade 3/4 AEs were neutropenia (29.5%, 26.5%, and 44.9%) and infections (31.6%, 21.9%, and 17.2%), and no new safety signals were seen compared with earlier analyses. Study discontinuation was most commonly due to disease progression and was less common in the Rd continuous vs Rd18 and MPT arms (50.7% vs 66.9% and 61.6%, respectively). Discontinuation due to AEs was similar across the Rd continuous, Rd18, and MPT arms (12.0%, 13.1%, and 13.9%). Solid tumor second primary malignancies (SPMs) occurred in 6.0, 6.9%, and 5.9% of pts, and hematologic malignancies occurred in 0.8%, 0.4%, and 2.6% of pts in the Rd continuous, Rd18, and MPT arms, respectively. Conclusions: Rd continuous significantly prolonged PFS and OS, and improved other secondary endpoints compared with MPT in transplant-ineligible pts with NDMM. Rd continuous also showed a PFS benefit compared with Rd18, delaying the time to next Tx. PFS2 outcomes suggest that Rd does not induce resistant relapses. Few hematologic malignancies occurred in the Rd arms, and the incidence of SPMs was similar between Rd continuous and Rd18. Rd continuous remains a standard of care for transplant-ineligible pts with NDMM. Disclosures Facon: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel and expense, Speakers Bureau. Dimopoulos:Genesis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene: Research Funding. Belch:Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Cavo:Bristol-Myers Squibb: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Millennium: Consultancy, Honoraria. Weisel:BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Onyx: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Ludwig:Janssen: Speakers Bureau; BMS: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau. Bahlis:BMS: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Onyx: Consultancy, Honoraria. Delforge:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Cavenagh:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Geraldes:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Oriol:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: 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. De La Rubia:Amgen, Bristol, Celgene, Janssen: Consultancy, Speakers Bureau. White:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria. Attal:janssen: Consultancy, Research Funding; amgen: Consultancy, Research Funding; celgene: Consultancy, Research Funding; sanofi: Consultancy. Ervin-Haynes:Celgene: Employment, Equity Ownership. Chen:Celgene: Employment, Equity Ownership. Houck:Celgene: Employment. Hulin:celgene: Honoraria; Bristol: Honoraria; Janssen: Honoraria; Amgen: Honoraria; takeda: Honoraria. Benboubker:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: 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.

Abstract Background: Contemporary approaches to non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) incorporate chemo-immunotherapy, biologic combinations, and immune modulating agents; toxicities in elderly pts (³65 years) receiving these therapies are not well studied. Further, clinical and biologic factors predicting these toxicities in pts receiving biologic therapy remain undefined. Methods: We reviewed data on NHL and/or CLL pts treated prospectively on 14 studies by the Alliance for Clinical Trials in Oncology from 2004-2014 (Table 1). Toxicity was assessed per the NCI CTCAE at the time of trial enrollment, and the probabilities of experiencing grade 3 and grade 4 hematologic (hem) and non-hematologic (non-hem) toxicities were modeled as a function of age (³65 years vs. < 65), time on study, treatment (biologics only vs. biologic + chemotherapy), gender, race, LDH, performance status (PS), stage, and an age-by-treatment interaction using logistic regression. Results: A total of 1199 pts (409 age ³ 65; 790 age < 65; 736=CLL and 463=NHL) were included. Among these patients, 493 received only biologic therapy (166 age ³ 65; 327 age < 65; 104 CLL; 389 NHL), and 706 received biologic + chemotherapy (243 age ³ 65; 463 age < 65; 632 CLL; 74 NHL). Among CLL pts (259 pts ³ 65), the effect of age on the probability of experiencing a grade 3 heme toxicity differed by treatment type (age-by-treatment interaction p = 0.047). Specifically, the adjusted odds ratio (OR) (age ³ 65 vs. < 65) for pts receiving only biologic therapy was 3.075 (95% CI: 1,15-8.25), and that for pts receiving biologic + chemotherapy was 1.044 (95% CI: 0.69 - 1.57). Similar results were seen in CLL pts for grade 4 heme toxicities (age-by-treatment interaction p = 0.033; biologic OR 6.937, 95% CI: 1.76-27.35; biologic + chemo OR 1.484, 95% CI: 1.04-2.13). No such interactions were found in CLL pts for grade 3 and 4 non-hem toxicities; however, older pts had significantly higher odds of experiencing a grade 3 non-hem toxicity than younger pts (adjusted OR 1.40; p = 0.047; 95% CI: 1.004-1.96). No age group differences were found in CLL pts for grade 4 non-hem toxicity. Similar analyses were performed for NHL pts (150 pts ³ 65), but no significant age group differences were found. Among CLL pts, women had significantly higher odds of experiencing a grade 3 heme toxicity than men (OR 2.01; p = 0.0007); no difference in grade 3 non-hem or any grade 4 toxicity was noted. Non-Caucasian CLL pts had higher odds of experiencing a grade 4 non-hem toxicity than Caucasians (OR 2.892; p = 0.0029), but no other toxicity differences were found. Worse PS was associated with increased toxicities (OR 1.871; p = 0.0009: grade 3 heme; OR 1.647; p = 0.0025: grade 3 non-hem; OR 1.410; p = 0.0448: grade 4 heme, and OR 1.931; p = 0.0252: grade 4 non-hem). CLL pts with advanced stage disease had higher odds of experiencing a heme toxicity (grade 3: OR 1.95; p = 0.0007, grade 4: OR 1.451; p = 0.0329), but no stage associations were found for non-hem toxicities. Among NHL pts, men had significantly higher odds of experiencing a grade 4 hematologic toxicity than women (OR 4.351; p = 0.0169), but no other toxicity differences were found. An increase in LDH was associated with significantly higher odds of experiencing grade 3 non-hem and grade 4 heme toxicities (grade 3 non-heme: OR 1.633; p = 0.021, grade 4 heme: OR 2.039, p = 0.0182), but no such effect was found for grade 3 heme or grade 4 non-hem. Worse PS was associated with higher odds of experiencing grade 3 toxicities (heme: OR 2.025; p = 0.0344, non-hem: OR 2.458; p = 0.0013), but no such differences were found for grade 4 toxicities. No significant stage or race effects were found in NHL patients. Conclusion: In pts ³65 years who have CLL or NHL, we identified several clinical and disease-related factors as potential predictors of developing grade 3 and/or 4 heme and non-hem toxicities (Table 2). A prognostic model is being constructed to predict toxicities in these under-studied pts to guide management and monitoring. Further, the impact of these toxicities on outcomes is being analyzed and will be presented at the meeting. Disclosures Hurria: Celgene: Other: Research; Optum Health Care SOlutions: Consultancy, Other: Conference panel, research; Boehringer Ingelheim Pharmaceuticals: Consultancy; Sanofi: Consultancy; Carevive: Consultancy; Novartis: Other: Research; GTx, Inc: Consultancy. Bartlett:Gilead: Consultancy. Cheson:Gilead: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nabhan:Infinity: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Seattle Genetics: Research Funding; Genentech: Consultancy, Research Funding; Astellas: Research Funding; Celgene Corporation: Consultancy, Research Funding.

Abstract Background We have previously reported on the high prevalence and severity of challenges with intimacy and sexuality amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between issues of intimacy (sexual desire and function), their relationships to MPN disease features, individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF sexuality item asked about “problems with sexual desire or function”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF sexuality item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the sexuality item with the final multivariate model selected using forward regression. Results Demographics A total of 1908 MPN patients (essential thrombocythemia=799, polycythemia vera=671, myelofibrosis=432, missing=6) completed the sexuality item. Participants were of typical age (median=60, range 15-94) and gender (female=53%). Overall, 1218 subjects described sexuality related complaints (score >0) with an overall mean symptom score of 3.5 (median=2.0, SD=3.7, range 0-10); 725/1908 (38%) patients had severe sexuality related complaints (score >4). Univariate Analysis Among the QLQ-C30 functioning scales, all domains had similar statistically significant correlations (r=-.26 to -.32, all p<0.001). Among QLQ-C30 symptom scales, all QLQ-C30 symptoms displayed correlations ranging between .08 and .29 (all p<0.001). Among MPN-SAF items, the MPN-SAF sexuality item correlated most significantly with the TSS (r=.41, p<0.001), along with MPN-SAF symptoms (r=.16 to .39; all p<0.001). MPN-SAF sexuality measure significantly differed by anemia (means: absent 3.3, present 4.5; p<0.001), leukopenia (means: absent 3.4, present 4.4; p=0.01), thrombocytopenia (means: absent 3.3, present 4.5; p<0.001), red cell transfusion (means: no 3.5, yes 5.0; p<0.001), MPN subtype (ET mean 3.1, PV mean=3.6, MF mean=4.4; p<0.001) and language (means ranged from 2.4 [Swedish] to 4.6 [Chinese]; p<0.001). MPN-SAF sexuality did not significantly differ by age, gender, prior thrombosis or prior hemorrhage. Multivariate Analysis In a multivariate model of MPN-SAF sexuality containing all QLQ-C30 functioning scales, physical (p=0.001), emotional (p=0.01), cognitive (p=0.005) and social (p=0.002) functioning were all statistically significant. Numerous symptoms were also significant in a multivariate model of MPN-SAF sexuality containing all other MPN-SAF symptoms (all p<0.05; abdominal pain, inactivity, dizziness/vertigo/lightheadedness, insomnia, depression/sad mood, cough, night sweats and overall QOL). The final multivariate model based on forward regression starting with all demographics, clinical variables, and patient-reported QLQ-C30 scales and MPN-SAF items found age, language, QLQ-C30 role functioning and MPN-SAF items (insomnia, depression/sad mood, night sweats and QOL) to be significant (p<0.05). Conclusions Sexuality related complaints have been linked to both physiologic and psychologic origins and are highly prevalent within the MPN population. The results of this study congruently identified close associations between sexuality and function within emotional, cognitive and social domains. Additionally, the correlations of sexuality issues with MPN symptoms and disease features further suggest this item is a key correlate of overall functionality and quality of life. Future investigations into the causative factors and biological correlates of this complaint may assist in addressing this ongoing challenge. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria. Mesa:Eli Lilly and Co: Research Funding; Genetech: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Sanofi: Research Funding; NS pharma: Research Funding; Celgene: Research Funding.

Abstract Background: Patients (pts) with refractory aggressive non-Hodgkin lymphoma (NHL) have poor outcomes with currently available therapies, with a complete response (CR) rate of 8%, a partial response (PR) rate of 18%, and median overall survival (OS) of 6.6 months (mo) as demonstrated in the 635 pt SCHOLAR-1 meta-analysis (Crump, ASCO 2016; abstract 7516). ZUMA-1 is the first multicenter trial of anti-CD19 chimeric antigen receptor (CAR) T cells in refractory, aggressive NHL (NCT02348216). The phase 1 portion of ZUMA-1 showed ongoing CRs at 12+ mos in 43% of pts (Locke, ESMO 2016; abstract 1048O). The pivotal phase 2 portion of ZUMA-1 comprises 2 cohorts based on tumor type: DLBCL (cohort 1) and primary mediastinal B-cell lymphoma or transformed follicular lymphoma (cohort 2). Here, we present results of a prespecified interim analysis from cohort 1. Methods: Pts received a target dose of 2 × 106 anti-CD19 CAR T cells/kg after a low-dose conditioning regimen of cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) daily for 3 days. The primary endpoint is objective response rate (ORR) per 2007 IWG criteria. Key secondary endpoints include duration of response, frequency of adverse events (AEs), and levels of CAR T cells and serum cytokines. Key inclusion criteria include age ≥18 years, ECOG performance status (PS) 0-1, and refractory disease defined as progressive disease or stable disease as best response to last line of therapy, or disease progression ≤12 mos after autologous stem cell transplant (ASCT). Pts must have received a prior anti-CD20 antibody and an anthracycline-containing regimen. A prespecified interim analysis was to be conducted to determine early efficacy with a nominal alpha level of 0.017 in 50 treated pts in cohort 1 with a minimum follow-up of 3 mos. Results: In total, 111 pts from 22 institutions were enrolled and leukapheresed, and 101 pts received KTE-C19. As of August 24, 2016, 51 pts in cohort 1 were eligible for analysis. Median age was 58 years (range, 25-76), 73% were male, 71% had ECOG PS 1, 78% were refractory to ≥2 lines of therapy, 20% relapsed ≤12 mos of ASCT, and 61% were treated with ≥3 lines of prior therapy. KTE-C19 was successfully manufactured in 99% of pts enrolled. Average turnaround time from apheresis to receipt of KTE-C19 at the clinical site was 17.4 days. With an ORR of 76%, the study met the primary endpoint (P<0.0001; exact binomial test comparing observed ORR to a historical control assumption of 20%), with 47% CRs and 29% PRs. 92% of responses occurred within the 1st mo, and 39% of pts had ongoing responses (CR in 33%) at 3 mos. Responses were seen across key covariates, including refractory subgroup (refractory to chemotherapy=76%, relapse post ASCT=80%). Kaplan-Meier estimates of progression-free survival at 1 and 3 mos were 92% and 56%, respectively. The most common grade ≥3 treatment-emergent AEs were neutropenia (67%), anemia (39%), thrombocytopenia (29%), febrile neutropenia (27%), and encephalopathy (24%). Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 20% and 29% of pts, respectively. There was 1 grade 5 KTE-C19-related event of hemophagocytic lymphohistiocytosis. CAR T cells expanded within 14 days of KTE-C19 infusion, and peak expansion was associated with ongoing response at mo 3 (P=0.008). Pts who developed grade ≥3 neurological events had increased serum levels of IL-15 (P=0.0002), IL-6 (P=0.003); IL-10 (P=0.009) and IP-10 (P=0.0003). Cytokines/chemokines returned to baseline levels in most pts by day 28. Data from 93 pts with at least 1 mo of follow-up at the data cutoff will be presented. Conclusions: ZUMA-1 is the first reported multicenter trial of CAR T cell therapy in pts with refractory aggressive NHL. KTE-C19 induced a nearly 6-fold higher CR rate compared to historical outcomes in SCHOLAR-1. Efficacy strongly associated with peak CAR T levels. Central manufacturing, logistics, and AE management were successfully implemented across 22 sites, most with no prior CAR T therapy experience. Results from cohort 2 of ZUMA-1 are also presented (Abstract #998). KTE-C19 demonstrated significant clinical benefit in pts with no curative treatment options. Supported in part by funding from The Leukemia & Lymphoma Society Therapy Acceleration Program®. Drs Neelapu and Locke contributed equally to this study. Disclosures Neelapu: Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding. Locke:Kite: Membership on an entity's Board of Directors or advisory committees. Miklos:pharmacyclics: Research Funding; Kite Pharma: Research Funding; Roche: Research Funding; Novartis: Research Funding. Jacobson:Kite: Membership on an entity's Board of Directors or advisory committees. Siddiqi:Pharmacyclics: Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Speakers Bureau. Lin:Mayo Clinic: Employment; Janssen: Research Funding. Timmerman:Bristol-Myers Squibb, Kite Pharma, Valor Biopharmaceuticals, Janssen: Research Funding; Seattle Genetics, Genmab, Celgene: Consultancy, Honoraria. Goy:COTA: Membership on an entity's Board of Directors or advisory committees; Janssen/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution; Acerta: 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, Speakers Bureau; Genentech: Other: Research funding for clinical trials through institution. Smith:Abbvie: Research Funding; Celgene: Honoraria; Spectrum: Honoraria; Genentech: Honoraria. Deol:Jazz Pharmaceuticals: Consultancy. Avivi:Tel Aviv Sourasky Medical center: Consultancy, Other: consultancy to :BMS Roche. Westin:Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; ProNAi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Chavez:Janssen: Speakers Bureau. Levy:Kite Pharma: Consultancy; Five Prime Therapeutics: Consultancy; Innate Pharma: Consultancy; Beigene: Consultancy; Corvus: Consultancy; Dynavax: Research Funding; Pharmacyclics: Research Funding. Reagan:Seattle Genetics: Research Funding. Bot:Kite Pharma: Employment, Equity Ownership. Rossi:Kite Pharma: Employment, Equity Ownership. Navale:Kite Pharma: Employment, Equity Ownership. Jiang:Kite Pharma: Employment, Equity Ownership. Aycock:Kite Pharma: Employment, Equity Ownership. Elias:Kite: Employment, Equity Ownership. Wiezorek:Kite Pharma: Employment, Equity Ownership. Go:Kite Pharma: Employment, Equity Ownership.

Abstract Background The international prognostic score (IPS) (Hasenclever et al., NEJM 1988) uses 7 factors (age> 45, male sex, hemoglobin<10.5, stage IV, leukocytosis > 15,000, and lymphopenia< 600) to predict a 5 year freedom from progression (FFP) of 42%-84% and overall survival (OS) of 56%-89% for patients with advanced HL. Constructed from a retrospective analysis of patients treated before 1992, the IPS continues to be the most commonly used risk stratification index for advanced HL. Recent studies suggest that the predictive range of the IPS has narrowed due to improved outcomes of patients treated with current therapy (Moccia et al. JCO 2012). In this report we prospectively evaluated the ability of the individual components of the IPS to predict outcome in patients enrolled on the US Intergroup trial E2496. Methods All seven IPS (IPS-7) variables were recorded for all patients at study entry. FFP was defined as the time from study entry to disease progression or relapse; deaths that occurred during remission that were not preceded by disease progression/relapse were censored. OS was defined as the time from study entry to death from any cause. Kaplan-Meier methodology was used to construct survival curves. Univariate and multivariate analysis (MVA) was performed using Cox proportional-hazards models. We subsequently constructed an alternative prognostic score utilizing the factors which were significant on MVA (PS-3). Results From 1996-2006, 854 patients with advanced HL, were randomized to treatment with either ABVD or Stanford V, with no significant differences in outcome (Gordon et al, JCO 2013). While the IPS-7 remained prognostic it did not stratify the lowest risk patients (0-1 risk factor) or patients with 3-5 risk factors, as its predictive range was narrowed due to improved clinical outcomes (Fig 1a and 2a). Table 1 shows the univariate and multivariate analysis for IPS-7 and outcomes. In contrast to the original IPS-7, on MVA, only two factors, hemoglobin and stage were significant for FFP, and three factors for OS: hemoglobin, stage, and age. We then evaluated a new 3 factor score (PS-3) utilizing variables significant on the MVA. The PS-3 was significant for both FFP (p=0.0001) and OS (p<.0001) and clearly separated patients into 4 distinct risk groups with either: 0, 1, 2 or 3 risk factors. The five year FFP was 83%, 74%, 68%, and 63% and OS was 95%, 85%, 75%, and 52% for patients with 0, 1, 2, and 3 risk factors, respectively (Table 2, Fig 1b and 2b). Conclusion In E2496, for patients with advanced HL, the PS-3 may stratify patients more clearly compared to IPS-7 and provide a simpler model to assess risk. Studies comparing PS-3 with IPS-7, and are ongoing. The incorporation of novel biomarkers and biologic factors into PS-3, as well as validation with other data sets is warranted. Disclosures: No relevant conflicts of interest to declare.

Abstract Background We have previously reported on the high prevalence and severity of insomnia amongst a large international cohort of MPN patients (Emanuel JCO 2012). We sought to further analyze the relationships between insomnia and the MPN disease features (in particular splenomegaly, status of blood counts), individual MPN symptom prevalence and severity, language, and overall quality of life. Methods Data was collected among an international cohort of patients with MPNs. Subjects completed the BFI, MPN-SAF, and EORTC QLQ-C30 instruments. Surveyed symptoms on the MPN-SAF included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. Specifically, the MPN-SAF insomnia item asked about “difficulty sleeping”. Total symptom score (TSS) was computed based on 10 symptom items using the published scoring algorithm on a 0 (all reported symptoms absent) to 100 (all reported symptoms worst imaginable) scale. Pairwise associations between the MPN-SAF insomnia item and continuous and categorical covariates were investigated using Pearson correlations and analysis of variance/t-tests, respectively. Multivariate regression models were used to investigate impact of groups of covariates on the insomnia item with the final multivariate model selected using forward regression. Results Demographics A total of 1992 MPN patients (essential thrombocythemia=834, polycythemia vera=703, myelofibrosis=449, unknown=6) completed the insomnia item. Participants were of typical age (median=61, range-15-94) and gender (female=54%). Overall, 1307 subjects endorsed the MPN insomnia item (score >0) with an overall mean symptom score of 3.0 (median=2.0, SD=3.1. range=0-10); 603/1992 (30%) of patients had severe insomnia related complaints (score >4). Univariate Analysis Among QLQ-C30 functioning scales, emotional functioning most highly correlated with the MPN-SAF insomnia item (r=-.47, p<0.001) with all other domains also having statistically significant but slightly weaker correlation (all p<0.001). Among QLQ-C30 symptom scales, insomnia (r=.79, p<0.001) and fatigue (r=.45, p<0.001) most highly correlated with the MPN-SAF insomnia item with all other QLQ-C30 symptoms having correlations between .13 and .37 (all p<.001). Among MPN-SAF items, the MPN-SAF insomnia item correlated with all MPN-SAF items (all p<0.001) including the TSS (r=0.55, p<0.001) and most highly with depression (r=.52, p<0.001), concentration problems (r=.43, p<0.001), overall QOL (r=.41, p<0.001), night sweats (r=.41, p<0.001), and extremity tingling (r=.40, p<0.001). MPN-SAF insomnia significantly differed by gender (means: M 2.4, F 3.4; p<0.001), language (means ranged from 2.6 [Italian] to 3.6 [German]; p=0.01), anemia (means: absent 2.8, present 3.5; p<0.001), prior hemorrhage (means: no 2.9, yes 3.7; p=0.01), and requiring red blood cell transfusion (means: no 2.9, yes 3.6; p=0.03), with a trend for a difference by MPN type (ET mean=2.7, PV mean=3.0, MF mean=3.2; p=0.06). Multivariate Analysis In a multivariate model of MPN-SAF insomnia containing all QLQ-C30 functioning scales, physical, emotional, and cognitive functioning along with global health status/QOL were all significant (all p<0.001). Numerous symptoms were also significant in a multivariate model of MPN-SAF insomnia containing all other MPN-SAF symptoms (all p<0.05: headaches, extremity tingling, depression, sexual problems, night sweats, pruritus, fever, and QOL). The final multivariate model based on forward regression starting with all demographics, clinical variables, and patient-reported QLQ-C30 scales and MPN-SAF items found age, gender, QLQ-C30 emotional functioning and MPN-SAF items to be significant. Conclusions Insomnia is highly prevalent and severe in MPN patients and closely correlates with most other MPN-related symptoms and functional domains bearing a multi-faceted impact on overall quality of life. Correlations between insomnia and emotional, cognitive, and physical complaints including depression/sad mood, concentration problems, night sweats, and numbness/tingling in the extremities suggest that the cause of MPN-related sleep complaints is likely complex. Future studies should evaluate the impact of interventions on MPN associated insomnia as well as its biological underpinnings. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

Abstract Background We have previously reported on the significant, but heterogeneous baseline MPN symptom burden among an international sample of MPN patients (including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)) utilizing the MPN Symptom Assessment Form (MPN-SAF) and the derivative Total Symptom Score (MPN-SAF TSS). Recent clinical trials have sought to determine optimal MPN symptom response criteria, such as absolute 10 point improvement in MPN SAF TSS for ET/PV (ELN Criteria, Barosi et. al. Blood 2013) and 50% reduction in MPN-SAF TSS for MF (IWG-MRT, Tefferi et. al. Blood 2013). We sought to determine the role of improvement in MPN-SAF TSS quartiles as potential thresholds to assess symptomatic response to therapy. Methods Utilizing prospectively gathered MPN-SAF TSS (Emanuel et. al. JCO 2012) in patients we assessed potential thresholds of response by evaluating quartile thresholds for severity of symptom burden. The MPN-SAF TSS was scored as the average of 10 symptoms (individual symptoms scores of 0-10, with a total score of 0 (best) to 100 (worst)). MPN-SAF TSS quartiles were identified by the percentage of scores between 0-24% (quartile 1 (Q1)), 25-49% (quartile 2 (Q2)), 50-74% (quartile 3 (Q3)), 75-100% (quartile 4 (Q4)). Results MPN-SAF TSS Quartiles: MPN-SAF TSS quartiles were identified among 1858 MPN patients (ET N=775, PV N=654, and MF N=423). Overall MPN-SAF TSS scores of 0 - 7 were designated as Q1, 8 - 17 as Q2, 18 - 31 as Q3, and ≥ 32 was as Q4. MPN-SAF TSS scores were significantly different between clusters (p<0.001). Associations Between Quartiles and Demographic/ Disease Factors: As quartiles increased, the proportion of PV and ET patients diminished and MF increased (Table 1, p<0.001). Cytopenias and transfusion dependence increased in prevalence in the higher quartiles (p<0.001). A history of prior thrombosis was also significantly more prevalent in the quartiles with highest symptom burden (p<0.001). The prevalence of women was significantly higher among the more symptomatic quartiles females 48.9% Q1, 49.4% Q2, 58.4% Q3, and 60.1% Q4; p<0.001). Associations Between Individual Symptoms and MPN-SAF TSS Quartiles: All individual symptoms measured in the MPN-SAF TSS were significantly worse in quartiles as they increased (p<0.0001). Evaluation of Prognostic Scoring and MPN-SAF TSS Quartiles: Comparison of each patients individual risk score (IPSET, PV, DIPSS for MF) and worsening symptom quartile showed the highest correlation with MF patients (DIPSS) (Table 1). However, ET and PV risk scores were not surrogates for symptom burden by quartile. Conclusions Distribution of MPN patient symptomatic burden by MPN-SAF TSS quartiles provides an easy-to-calculate method to cluster and analyze MPN patients of similar burden. Although MF patients are most prevalent in the most severe quartile of MPN symptomatology it is notable that Q4 has many patients with PV and ET. Future prospective efforts are ongoing to assess the potential of using changes in quartile (i.e. improving from Q3 to Q1) as potential symptomatic response thresholds. Disclosures: Etienne: novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees. Roy:Novartis, BMS: Honoraria. Harrison:Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Shire: Speakers Bureau; Celgene: Honoraria; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Vannucchi:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Birgegard:Vifor Pharma: Honoraria.

AbstractRecent analyses of circulating blood B cells in myeloma have generated controversy concerning the exact levels of these cells and whether they may represent circulating clonal tumor B cells. Previous reports suggested that CD19+ B cells are markedly increased in myeloma patients and that this population shares clonotypic rearrangements with the malignant plasma cell. We studied the numbers of CD19+ B cells by flow cytometry in previously untreated newly diagnosed myeloma patients in Eastern Cooperative Oncology Group (ECOG) phase III trial E9486. There were 628 patients who were eligible for the clinical protocol E9486, but of these 521 were also entered on the companion laboratory study (E9487) and had CD19 data. In comparison with normal controls, the myeloma patients exhibited a marked heterogeneity in the number of circulating CD19+ B cells as detected by flow cytometry. Approximately 20% of patients had significantly increased levels of circulating CD19+ B cells. However, the total CD19+ blood population from myeloma was not significantly different from the median of age-matched, normal controls. Analysis of CD19+ blood cells in relationship to circulating clonal cells was done in 13 myeloma patients using a clonotypic, quantitative allele-specific oligonucleotide-polymerase chain reaction (PCR) assay. No correlation was found between the numbers of CD19+ B cells (range, 5% to 51%) and PCR estimates of the number of clonal cells in the peripheral blood (range, .009% to 3.6%). Low CD19+ B-cell level (&lt;125 μL) was associated with clinical stage III (P = .033). A significant relationship exists between higher levels (≥125/μL) of CD19 cells and longer overall survival (P &lt; .0001). In addition, high CD19 levels also predicted a clinical response and longer event-free survival. There was a strong inverse association between the level of CD19 values at diagnosis and infections within the first 2 months of diagnosis. Importantly, the number of deaths related to infections was significantly greater in the low versus high CD19 group (P &lt; .0202). Also, CD19 is an independent prognostic factor in addition to plasma cell labeling indices, β2 -microglobulin, hemoglobin, and plasmablastic morphology. Patients with infections were more likely to have low levels of CD19+ cells. In summary, higher CD19+ cell levels are a favorable prognostic sign with no apparent relationship to circulating tumor cells. In addition, this analysis strongly suggests that low peripheral blood levels of CD19+ cells are an adverse prognostic sign in myeloma. The CD19+ cell levels in myeloma patients is an important parameter in the overall assessment of these patients.

Abstract Background Outcomes for patients with DLBCL have improved over the past decade, with the addition of rituximab to CHOP or CHOP-like multi-agent chemotherapy regimens improving the 3-year overall survival (OS) of patients by 10-16% compared to multi-agent chemotherapy alone (Coiffier 2002; Pfreundschuh 2010). However, patients with high-intermediate or high-risk disease have relatively poor outcomes with the standard RCHOP regimen (Ziepert 2010); in a recent prospective trial of intermediate- and high-risk DLBCL patients, complete response (CR) rate for RCHOP alone was 26% (Hainsworth 2011). Brentuximab vedotin (ADCETRIS®) is an antibody-drug conjugate comprising the antibody cAC10, specific for human CD30, covalently attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Brentuximab vedotin has demonstrated compelling activity as a single agent in patients with relapsed or refractory DLBCL, even those with low CD30 expression (Bartlett 2013). This phase 2, randomized, open label study is designed to evaluate the antitumor activity and safety of brentuximab vedotin (1.2 or 1.8 mg/kg) when administered in combination with standard RCHOP chemotherapy (A+RCHOP) for the front-line treatment of patients with CD30-unselected high-intermediate/high-risk (standard IPI score 3–5 or age-adjusted IPI [aaIPI] score 2–3) DLBCL (ClinicalTrials.gov NCT01925612). Methods Patients were randomized to receive up to 6 cycles of either 1.2 or 1.8 mg/kg brentuximab vedotin administered IV on Day 1 of every 21-day cycle in combination with RCHOP; prednisone was administered orally on Days 1-5 of every 21-day cycle. Assessments included disease response per Cheson 2007, as evaluated by the investigator, surveillance of adverse events (AEs), physical examination findings, and laboratory testing. The primary endpoints for this study are the CR rate at the end of treatment (EOT) and the type, incidence, and severity of AEs. Key secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and OS. Results At the time of the planned interim analysis, 33 patients were enrolled (17 patients, 1.2 mg/kg A+RCHOP; 16 patients, 1.8 mg/kg A+RCHOP). Median age for all patients was 66 years (range, 21 to 81). At baseline, 36% were high-risk (IPI 4-5, aaIPI 3) and 64% were high-intermediate risk (IPI 3, aaIPI 2). The majority of patients (73%) had Stage IV disease and 33% had an ECOG status of 2. At the time of interim analysis, a total of 12 patients (6 patients in each arm) had completed EOT. Across both dose levels, ORR was 92% (11/12), with 7 CRs (58%), 4 PRs (33%), and 1 PD. The patient with PD subsequently died. Patients with PR had a median reduction of baseline tumor size of 84% (range, 92% to 83%), as measured by SPD. The only patient with follow-up after EOT converted from PR to CR without subsequent therapy. Treatment-emergent AEs occurring in ≥30% of patients treated (26/33) were nausea, diarrhea, peripheral sensory neuropathy, fatigue, and decreased appetite. Grade 3 or higher events occurring in more than 2 patients were febrile neutropenia and neutropenia. Events of peripheral neuropathy occurred equally per arm (46%, 1.2 mg/kg A+RCHOP; 46% 1.8 mg/kg A+RCHOP) and were generally Grade 1 or 2 (15% and 23%, respectively); events were of similar grade across dose levels. The median time to onset of any grade of peripheral neuropathy was 6 weeks (range, 2 to 10 weeks). Five patients (19%) had dose reductions due to peripheral neuropathy and 3 patients (12%) had dose reductions due to febrile neutropenia. One patient who received 1.2 mg/kg A+RCHOP discontinued study drug due to an AE (thrombocytopenia). Conclusions At doses of 1.2 or 1.8 mg/kg, A+RCHOP exhibited manageable toxicity in the treatment of newly-diagnosed DLBCL; the incidence of peripheral neuropathy was similar to single-agent administration of brentuximab vedotin (Pro 2012, Younes 2012) and RCHOP alone (Rummel 2013, Flinn 2014). In 12 patients with response-assessable, high-intermediate and high-risk DLBCL, A+RCHOP showed encouraging antitumor activity, with an ORR of 92% and a CR rate of 58%. Disclosures Yasenchak: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. . Farber:Seattle Genetics, Inc.: Research Funding. Budde:Seattle Genetics, Inc.: Research Funding. Ansell:Seattle Genetics, Inc.: Research Funding. Advani:Takeda Pharmaceuticals International Co.: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Jansseen Pharmaceuticals: Research Funding; Genentech: Research Funding; Seattle Genetics, Inc.: Research Funding, Travel expenses Other. Holkova:Seattle Genetics, Inc.: Research Funding. Halwani:Seattle Genetics, Inc.: Research Funding. Knapp:Takeda Pharmaceuticals International Co.: Research Funding; EMD Serono: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Merck: Research Funding; Heron Pharmaceuticals: Research Funding, Travel expenses, Travel expenses Other; Genentech: Research Funding, Travel expenses, Travel expenses Other; Seattle Genetics, Inc.: Research Funding; Pharmacyclics: Research Funding. Fayad:Seattle Genetics, Inc.: Consultancy, Research Funding. Kolibaba:Genentech: Research Funding; Takeda Pharmaceuticals International Co.: Research Funding; Seattle Genetics, Inc.: Research Funding. Patel-Donnelly:Seattle Genetics, Inc.: Research Funding. Seetharam:Seattle Genetics, Inc.: Research Funding. Manley:Seattle Genetics, Inc.: Employment, Equity Ownership. Bartlett:Genentech: Research Funding; ImaginAb: Research Funding; Celgene: Research Funding; MedImmune: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Pfizer: Research Funding; Takeda Pharmaceuticals International Co.: Research Funding; Seattle Genetics, Inc.: Research Funding, Travel expenses Other; Janssen: Research Funding; Astra Zeneca: Research Funding.