ALBERT

Description: Introduction Transformation of chronic lymphocytic leukemia (CLL) into Hodgkin lymphoma (HL) is a rare, but recognized complication of CLL. The prognosis of CLL with HL Transformation (HT) appears significantly worse than de novo HL, but most series are small and there are limited published data. These reports have prompted several groups to recommend aggressive therapy with stem cell transplantation (SCT) in first complete remission (CR1). We describe the largest reported series of HT patients (pts) with analyses of the clinicobiologic characteristics, treatment patterns, and clinical outcomes based upon our multi-institutional clinical experience. Methods Pts diagnosed with HT from 01/2000 - 01/2018 were retrospectively identified in 13 tertiary cancer centers. Clinicobiologic characteristics, treatment type, and survival outcomes for each pt were analyzed. Overall survival (OS) was measured from the time of HT diagnosis until time of death. OS estimates were calculated using the Kaplan-Meier method. The log-rank test was used to calculate differences in survival. Results Ninety-four pts with HT were identified. Median age at HT was 67 years (yrs; range, 38-85) and 81% of the pts were male. Median time from CLL diagnosis to HT was 5.5 yrs (range, 0-20.2; 7 pts with simultaneous diagnosis of CLL and HL). At initial CLL diagnosis, 31%, 34%, 21%, 10%, and 4% were Rai Stage 0, 1, 2, 3, and 4, respectively. At CLL diagnosis, 67% (25/37) had an un-mutated IgVH gene, 36% (21/59) had del(13q), 32% (14/44) had trisomy 12, 24% (14/59) had del(11q), and 15% (9/61) had del(17p). Prior to HT diagnosis, pts had a median of 2 (range, 0-12) therapies for CLL. Seventeen (18%) had no prior CLL treatments. Forty-three (46%) and 25 (27%) patients had received purine analogue- and ibrutinib-based therapy prior to HT, respectively. Baseline characteristics at HT are described in Table 1. As initial therapy for HL, the majority of pts (61%, n = 62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine) at full (n = 48) or reduced (n = 14) doses. Of these, CD20 monoclonal antibody was added in 6 and Bruton-tyrosine kinase inhibitor was added in 2. Ten (11%) received a brentuximab-based regimen. Seven (7%) received an RCHOP-based regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Six patients (6%) received no therapy for HT due to frailty. Subsequent therapy included autologous SCT and allogeneic SCT in 7 (7%) and 11 (12%) of patients, respectively. Two (2%) and 5 (5%) pts received their autologous and allogeneic SCT while in CR1, respectively. The median number of treatments for HT per pt was 1 (range, 0-5) with 59 (61%) pts only receiving one line of therapy. After HT diagnosis, pts had a median follow-up of 1.6 yrs (range, 0.0 - 15.1). Two-yr OS after HT diagnosis was 72% (95%CI 62 - 83%). The pts who received any CLL directed therapy (n = 80) prior to HT had a significantly lower estimated 2-yr OS of 69% (95%CI 58 - 82%) compared with pts who did not receive any prior CLL-directed therapy (n = 17; 93%; 95%CI 82-100%; p 0.02; Figure 1). Pts who received purine-analogue-based therapy for their CLL prior to HT had a significantly lower estimated 2-yr OS of 60% (95%CI 46 - 79%) compared with pts who did not receive purine-analogue-based CLL-directed therapy prior to HT (n = 51; 83%; 95%CI 73 - 96%; p 0.009; Figure 2). Although limited by small sample size, the pts who underwent SCT for HT in CR1 had a similar 2-yr OS (n = 7; 67%; 95%CI 38-100%) to pts who did not undergo SCT for HT in CR1 (n = 87; 72%; 95%CI 63 - 84%; p 0.46; Figure 3). Conclusions In this retrospective analysis, we describe the largest reported series of pts with HT from CLL. Two-yr survival in pts with HT was shorter than what is historically expected in patients with de novo HL, but longer than what is expected in CLL pts who transform to diffuse large B-cell lymphoma. Pts with HT who have received prior CLL-directed therapies (specifically purine-analogue-based treatments) are estimated to have a shorter 2-yr OS, likely due to underlying immunosuppression. The majority of pts (61%) only received 1 line of HL therapy and only 20% went on to receive SCT (7% while in CR1), indicating that these patients can have prolonged OS after achieving response to first-line therapy for HT and may not require SCT in CR1. Further study of this rare population is required to determine optimum management. Disclosures Kander: AstraZeneca: Consultancy. Parikh:Gilead: Honoraria; AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen: Research Funding; MorphoSys: Research Funding; Pharmacyclics: Honoraria, Research Funding. Shadman:Acerta Pharma: Research Funding; Verastem: Consultancy; Celgene: Research Funding; Gilead Sciences: Research Funding; Mustang Biopharma: Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Consultancy; Beigene: Research Funding; Genentech: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy; AbbVie: Consultancy; TG Therapeutics: Research Funding; Genentech: Consultancy. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Mato:Portola: Research Funding; AstraZeneca: Consultancy; Acerta: Research Funding; Prime Oncology: Honoraria; Regeneron: Research Funding; Celgene: Consultancy; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; Medscape: Honoraria; TG Therapeutics: Consultancy, Research Funding; Johnson & Johnson: Consultancy; AbbVie: Consultancy, Research Funding. Hill:Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: 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; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: 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; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Danilov:Verastem: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Astra Zeneca: Consultancy; Gilead Sciences: Consultancy, Research Funding. Phillips:Abbvie: Research Funding; Bayer: Consultancy; Gilead: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy. Brander:Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Novartis: Consultancy, Other: DSMB; Teva: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding. Smith:BMS: Consultancy; Portola: Honoraria. Davids:Surface Oncology: Research Funding; Roche: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Surface Oncology: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; MEI Pharma: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Research Funding; Roche: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; BMS: Research Funding; MEI Pharma: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy; Merck: Consultancy; Celgene: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Celgene: Consultancy; BMS: Research Funding; Surface Oncology: Research Funding; MEI Pharma: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding.

Description: Introduction: Venetoclax (VEN) based therapy has become a standard of care in front line and relapsed-refractory (R/R) CLL based on favorable efficacy and toxicity. Whereas prospective data regarding activity of therapies following ibrutinib (IBR) or idelalisib (IDE) are available in the settings of progression (VEN, non-covalent BTKi) and intolerance (acalabrutinib), how best to manage patients (pts) who discontinue (dc) VEN remains a key unanswered question. With the increased use of VEN in early lines of therapy (LOT; CLL 14, MURANO), the activity of BTK inhibitors (BTKi) and cellular therapies following VEN becomes a critical issue. No prospective study has addressed this question, and currently reported VEN clinical trials have limited information about subsequent treatments. While recent data describe VEN resistance mechanisms (Guieze 2018, Blombery 2019), the impact of VEN resistance on efficacy of post VEN therapies is unknown. To address this gap, we conducted an international study to identify a large cohort of pts who dc VEN and have been subsequently treated. Methods: We conducted an IRB approved multicenter (31 US, EU, South American sites, in partnership with UK CLL Forum and CORE registry), retrospective cohort study of CLL pts who dc VEN for any reason. We examined demographics, dc reasons, responses, survival, adverse events (AEs) and activity of post VEN therapies. Primary endpoints were overall response rate (ORR) and progression free survival (PFS) for the post VEN treatments stratified by treatment type (BTKi, PI3Ki and cellular therapy: CAR-T or alloHSCT). ORR was defined by iwCLL criteria and PFS was defined from VEN dc to disease progression (PD), death, or last follow up for next treatment. Pts were further stratified by BTKi (resistant / intolerant) and PI3Ki exposure prior to VEN. PFS-2 was defined as time from VEN start to tumor progression on IBR or death from any cause. Results: 326 CLL pts who dc VEN in the front line (4%) and R/R settings (96%) were identified. The cohort was 69% male, 87% white, median (med) age 66 (38-91) at VEN start, 27% treated with VEN based combinations (n=88, med 6 cycles anti-CD20 abs). Pre VEN prognostic features: 82% IGHV unmutated (n tested=166), 47% del17p (n=306), 45% TP53 mut (n=217), 39% complex karyotype (n=273), 23% BTK mut (n=79), 18% NOTCH1 mut (n=103), 10% PLCγ2 mut (n=74). Pts received med 3 therapies (0-11) prior to VEN; 40% were BTKi naïve (n=130), 60% were BTKi exposed (196) and 81% were IDE naïve (n=263). Most common reasons for VEN dc were PD (38%), AE (20%), Richter's transformation (RT, 14%), 8% pt preference, and HSCT 5%. Of 326 pts who dc VEN, 188 (58%) were treated with a subsequent LOT, 61 are alive and untreated and 77 died prior to a subsequent LOT. Post VEN sequencing analyses focused on BTKi, PI3Ki and cellular therapy (CAR-T or alloHSCT) activities following VEN dc (Table1). ORR to BTKi was 84% (n=44) vs. 54% (n=30, p

Description: Introduction: Venetoclax (Ven) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (Ven mono) or in combination (Ven paired) with rituximab based on clinical trials with selected patients (pts) and limited ibrutinib exposure. Whether Ven paired is superior to Ven mono, patterns of care, and outcomes following Ven discontinuation are unknown. Further, better delineation of adverse events (AEs) when Ven is used outside of clinical trials is needed. To address these gaps, we conducted a multicenter, international study in partnership with CLL Collaborative Study of Real World Evidence (CORE) and UK CLL Study Forum examining the clinical experience of 348 Ven treated CLL pts, representing the largest series of Ven treated pts reported to date. Methods: We conducted a retrospective cohort analysis of CLL pts treated with Ven across 24 US and 42 UK academic and community centers. We examined demographics, baseline disease characteristics, dosing, AEs, TLS risk and outcomes, response rates, outcomes (overall survival (OS) and progression free survival (PFS)), and tx sequencing. TLS events were defined by Howard criteria. PFS and OS were estimated by the Kaplan Meier method. Comparisons of outcomes used the Log Rank test. Univariate and multivariate analyses were performed with COX regression. All other comparisons were descriptive. Results: Of these 348 CLL pts, 94% were R/R, median age 67 years (range:37-91), 69% male, 85% white, and 73% Rai stage ≥2. 19% received Ven on clinical trial. 79% had Ven mono; Ven was paired most commonly with anti-CD20 (n=51) and ibrutinib (n=10). Pts received a median of 3 tx (range 0-15) before Ven; 78% received ibrutinib, 29% received PI3Ki, 20% had ≥2 prior kinase inhibitors, and 68% had chemoimmunotherapy. Median time from most recent tx to Ven start was 1.1 months (range 0-62). Pre-Ven prognostic markers included 43% del17p, 34% TP53 mutated, 24% del11q, 38% complex karyotype (≥ 3 abnormalities), and 84% IGHV unmutated (Table 1). TLS risk was low in 38%, intermediate in 34% and high in 28%. During ramp up, TLS was observed in 10% (22 lab, 9 clinical TLS events, 3 missing data). Following dose escalation, 70% achieved a stable Ven dose of 400 mg, 33% required ≥ 1 dose interruption and 27% required ≥ 1 dose reduction. AEs included grade 3 neutropenia 39%, grade 3 thrombocytopenia 29%, infections 25%, grade ≥ 2 diarrhea 7.8%, and neutropenic fever 7.7%. AEs were similar whether treated on or off clinical trial. The ORR to Ven mono, Ven paired was 81% (34% CR), 86% (29% CR). With a median follow-up of 14.2 months, median PFS and OS were not reached (12 month PFS 74%, OS 82%). Figure 1 depicts PFS stratified by Ven mono vs. paired, clinical trial vs. clinical practice, del17p status, and complex karyotype. Pts who discontinued Ven due to AEs had better OS compared with those who discontinued due to progression or Richter Transformation (RT) (Median OS 47 vs. 15.1 vs. 8.6 months, respectively). In multivariate analyses, complex karyotype was the only independent predictor of PFS (HR 2.8, p

Description: Abstract 3029 Background: In patients with hematologic malignancies undergoing myeloablative hematopoietic stem cell transplantation (HSCT), an elevated serum ferritin prior to HSCT has been consistently associated with increased mortality. While serum ferritin is strongly correlated with liver iron content (LIC), to date no study has directly examined the effect of elevated LIC on HSCT outcomes. Furthermore, there are no studies of pre-transplantation chelation in this population. We conducted 2 prospective studies in patients with AML, ALL, or MDS undergoing HSCT. In the first, 45 patients were followed for 〉1 year with serial measurements of serum iron parameters and liver and cardiac iron (by MRI). In the second, we treated patients with severe iron overload (ferritin ≥ 1000 ng/ml and liver iron content (LIC) ≥ 5 mg/gdw) with deferoxamine 50 mg/kg/d starting in the weeks prior to transplantation and continuing until day -1, with the goal of controlling labile plasma iron (LPI) and especially the expected conditioning-induced rise in LPI. Results: The baseline characteristics of the patients on the observational study have been described in a prior publication (Armand et al., BBMT 2011). 5 patients (2 with AML in CR, 2 with AML and active disease, 1 with MDS) were enrolled on the chelation study; the median serum ferritin was 3, 746 ng/ml, and LIC 11.7 mg/gdw. They received deferoxamine for a median of 19 days before stem cell infusion. No significant drug-related toxicity occurred except for one episode of transient hypotension. There was no significant change in LIC after this short course of chelation. None of the 5 patients had a positive LPI assay before chelation or at the onset of conditioning; however, despite deferoxamine treatment, 2/5 had elevated LPI post-conditioning. Among those 5 patients, there was no disease relapse or death at a median follow-up of 20 months; only 1 patient developed grade II acute GVHD, and no patient developed VOD. Among the 50 patients in both studies combined, there was no significant change in serum ferritin, LIC or cardiac T2* in the first year after HSCT. After a median follow-up of 24 months, the estimated 2y overall survival (OS) and progression-free survival were 54% and 46%, respectively. When patients on the chelation study were excluded, there was a significant difference in OS for patients with pre-HSCT ferritin 〉 2, 500 ng/ml (2y OS 21% versus 62%, p =0.03) (Figure, panel A), similar to prior studies. However, there was no difference in OS, PFS, relapse or NRM for patients stratified by pre-HSCT LIC, regardless of the cutoff used and whether or not chelated patients were included (Figure, panel B). There was also no discernible impact of LIC on acute GVHD or VOD incidence. The difference in OS based on ferritin was apparent even among the patients with LIC

Description: Abstract 3332 Poster Board III-220 Introduction Iron overload is a recently recognized problem for patients undergoing hematopoietic stem cell transplantation (HSCT). Hyperferritinemia is common and is associated with significantly increased treatment-related mortality (TRM) and poorer overall survival after HSCT. However, serum ferritin may be a poor surrogate for total body iron burden, and no prospective study of parenchymal iron overload has yet been reported. We initiated a prospective study of adult patients with acute leukemia or myelodysplastic syndrome (MDS) undergoing myeloablative HSCT, in order to estimate the prevalence of iron overload in this population. We measured pre-HSCT serum ferritin, C-reactive protein (CRP), iron, total iron binding capacity, and genotyped patients for HFE mutations. All patients also underwent liver and cardiac MRI with measurement of T2*, from which liver iron content (LIC) and cardiac iron loading were inferred. Results 41 of 45 planned patients have been enrolled to date. Median age was 46 years (range, 18-63). 24 patients had AML, 11 had ALL, and 6 had MDS. They had received a median of 2 prior chemotherapy courses (range, 0-6). Among the 39 patients with available transfusion history, the median number of prior RBC transfusions was 19 (range, 0-59). 88% of patients had a pre-HSCT serum ferritin above normal; the median value was 1432 (range, 20-6989). Higher ferritin values were associated with more advanced disease stage, number of prior chemotherapy regimens, and number of transfusions. The median LIC was 3 g/g dry weight (g/gdw) (range, 0.6-12.9). 85% of patients had an LIC above the upper limit of normal (1.8 g/gdw), and 17% had an LIC above 7 g/gdw. Only 1 patient had cardiac iron overload (cardiac T2*

Description: Introduction: Venetoclax (Ven), an oral BCL2 inhibitor, is approved for the treatment (tx) of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Ven is generally well tolerated, and side effects observed in clinical trials have been consistent with other CLL tx. Clinical trials using the approved dose escalation schedule report negligible rates of clinical tumor lysis syndrome (TLS). We aimed to understand rates of select adverse events (AEs) including cytopenias, infections, and TLS in CLL patients (pts) treated with Ven in community and academic settings. To do so, we examined 297 pts with CLL who received Ven, either alone or paired, in this multicenter, international study. Methods: We conducted a retrospective cohort study of Ven treated pts with CLL across at 15 academic (n=169) and 51 community (n=128) centers outside of the clinical trial setting. This study represents a collaboration between US centers, CLL Collaborative Study of Real World Evidence (CORE), and UK CLL Forum. Demographics, baseline disease characteristics, Ven dosing, TLS risk (per FDA Ven label) and prophylaxis, and AEs were collected. Lab vs. clinical TLS was defined by Howard criteria. PFS was estimated by Kaplan Meier methodology. All comparisons were descriptive. Results: Of the 297 pts examined, median age at Ven initiation was 67 (range 37-91). The group was 69% male, 96% had R/R CLL, and 45% had del17p. Baseline characteristics stratified by practice setting are included in Table 1. 80% received Ven as monotherapy while 20% received it paired with another agent (anti-CD20 mAb (75%), ibrutinib (8.5%), other (16.5%)). All pts were treated outside of clinical trials. During dose escalation, 81% achieved a 400 mg dose and 65% maintained 400 mg following escalation (cyp3A4 use unknown). TLS risk was low in 40%, intermediate (int) in 32%, and high risk in 28%. CT scan prior to Ven initiation was performed in 62%. At least one hospitalization occurred for 56% of low, 80% of int, and 88% of high risk pts (63% of the total cohort). Table 1 describes the distribution of TLS risk and frequency of hospitalizations in academic, community centers. TLS prophylactic measures were available for a subset of pts. Allopurinol was used for 91% (n=68/75) of low, 93% (n=52/56) of int, and 94% (n=29/31) of pts at high risk for TLS. Rasburicase was used for 27% (n=28/102) of low, 42% (n=34/81) of int, and 72% (n=57/79) of high risk pts. Normal saline was used in 85% (n=62/73) of low, 88% (n=49/56) of int, and 97% (n=30/31) of high risk pts. TLS occurred in 8.4% of pts (n=25/297). Three lab and 2 clinical events occurred in low risk pts, 7 lab and 3 clinical events in int risk pts, and 7 lab and 3 clinical events in high risk pts. Of pts with TLS, 1 has discontinued Ven. Of pts with clinical TLS, all were hospitalized, received allopurinol and normal saline, and 28% received rasburicase. 72% with TLS had creatinine clearance

Description: Introduction: T cell lymphomas are heterogenous with an overall poor prognosis. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T cell lymphoma (AITL) are the two most common subtypes in the US accounting for 45% of diagnoses. Based on overlapping recurrent molecular and cytogenetic abnormalities, the WHO created an umbrella category of nodal T-cell lymphomas with T-follicular helper phenotype (TFH lymphoma), which includes AITL and PTCL with TFH phenotype (Swerdlow SH, et al. Blood. 2016). 25-30% of patients (pts) are refractory to initial therapy and even amongst responders to initial therapy, relapse is common. Survival after relapse or progression (R/P) is typically measured only in months. Outcomes have not changed significantly even with the introduction of several new agents in the last 10 years (Chihara D, et al. Br J Haematol. 2017). There remains no standard 2nd line therapy or guidance on sequencing of therapies as interpretation of clinical data in T-cell lymphoma is frequently hampered by the heterogeneity of the patient population and small sample size. The aim of our study was to determine outcomes in a large, well-defined group of pts with either primary refractory PTCL-NOS or TFH lymphoma. Methods: We performed a multi-center retrospective study to determine outcomes to 2nd line therapy for adult pts diagnosed between 1.1.09-6.30.18 with PTCL-NOS or TFH lymphoma, who were primary refractory defined by either induction failure, less than CR to initial therapy, or relapse within 6 months (mo) of completion of initial therapy. We performed time to event analysis using Kaplan-Meier method and compared groups using log-rank test. All other statistics were descriptive. Results: Patient and disease characteristics at diagnosis and relapse are summarized in Table 1. We identified 80 eligible pts from 7 US academic centers. Median FU was 17.2 mo from diagnosis (0.5-70). Overall, pts had mostly advanced stage with multiple high-risk features including bone marrow (BM) or extranodal (EN) involvement and B symptoms at diagnosis and R/P. Most pts received CHOP (52%) or CHOEP (24%) as initial therapy. 60% of patients did not attain a CR, while 40% of pts relapsed after initial CR.14% had received a consolidative transplant in 1st CR prior to relapse (almost all autologous hematopoietic cell transplant [HCT]). At R/P, 48% received single agent therapy [mostly romidepsin (15/38)], while 36% received multi-agent salvage therapy [mostly ICE (9/29)]. 13/80 pts were placed on hospice or only received local therapy after R/P. Median OS from diagnosis and following R/P was 19 mo/12.9 mo respectively. Median PFS2 (defined as time from 2nd line therapy to 2nd progression) for pts receiving systemic therapy was 73 days (d) (range 41-175). On univariate and multivariate analysis, there was no significant difference in PFS2 by histologic subtype (74 d for PTCL and 73 d for TFH lymphoma; p=0.29), platelet count

Description: Introduction: Musculoskeletal toxicities are common in CLL patients (pts) treated with ibrutinib (Ibr) in both upfront and relapsed/refractory (R/R) settings. Importantly, arthralgias/myalgias (A/M) are among the most common reasons for discontinuation of Ibr due to toxicity in reported series (Mato, Ann Oncol, 2017; Mato, Haematol, 2018). Despite this, there are no detailed descriptions and limited guidance for management of A/M. Methods: To characterize this syndrome and its management, we retrospectively analyzed a cohort of 128 pts treated with Ibr at a single academic center from 2011-2017. Demographics, prognostic factors, concomitant statin use, as well as Ibr dose reductions/dose holds, use of NSAIDs/corticosteroids, and the supplement CoQ10 were collected. A/M were graded using CTCAE v4.0 when available, or per physician description as mild, moderate, or severe. Due to clinical difficulty in separating joint and periarticular soft tissue and/or muscle symptoms, we combined arthralgias and myalgias into a single toxicity defined by the most severe grade. Log rank (LR) test was used for comparison of covariates with outcomes. All other statistics were descriptive. Results: Demographics are summarized in Table 1. The cohort was predominantly male (75%) and Caucasian (95%); 50% received Ibr as front-line therapy and starting dose was 420 mg in 92% pts. 29 pts (24%) had 17p deletions and 26 (20%) had 11q deletions. 48 pts (38%) were on a concurrent statin. 48 (35%) pts developed A/M (20 frontline treatment, 28 R/R). Mean time to development was 349 days (range 7 -1162). 27/48 (56%) developed A/M 〉6 months from start of Ibr. 39/48 (82%) A/M events were described as mild or moderate (71% Grade 1/2; 19% Grade 3 per CTCAE). 37/48 (77%) of pts had a partial response or partial response with lymphocytosis at the onset of symptoms. 19/48 (39%) pts developed A/M while on a statin. Management and outcomes are described in Table 2. 15/48 (31%) were managed by Ibr hold and 20/48 (42%) by dose reduction; 9/48 (19%) had both. Mean hold duration was 17.5 days (range 2-67). Dose hold was successful in 6/15 (40%) pts, while dose reduction alleviated symptoms in 6/20 (30%); statins were discontinued in 5/17 (29%) pts. Corticosteroids (4 pts) and CoQ10 (4 pts) were used in conjunction with dose holds and dose reductions with symptomatic improvement in 2 and 4 pts, respectively. 4 pts used NSAID or acetaminophen without improvement in symptoms. 2 pts required opiate analgesics for pain management. 29/48(60%) had resolution of A/M during follow up. Overall, no changes in therapy were made in 19 (48%) pts and 13 (68%) had spontaneous resolution of symptoms. Of these patients, 12 had Grade 1 A/M. 40% of pts' A/M persisted, 13/19 (68%) had dose reduction, 8/14 (57%) had a dose hold, 7/16 had both, and 5/19 (26%) had no intervention. Management and outcomes did not differ if A/M occurred before or after 6 months. In this cohort, 46/128 (36%) of pts discontinued Ibr: 11/128 (9%) for toxicity related to A/M; 19/128 (15%) for other toxicity; 10/128 (8%) for disease progression; 5/128 (4%) for transformation; 2/128 (2%) other reasons. Median time to discontinuation of Ibr for A/M was 23.3 mo (1-56.8 mo). Concurrent statin use and statin dose intensity were not associated with increased risk of developing A/M by LR test. Based on our observations, we suggest the following algorithm for the management of Ibr-associated A/M (Figure 1): if A/M do not interfere with ADLs, continue Ibr at current dose and monitor closely for symptom progression, as cases can resolve without intervention. If symptoms affect ADLs, hold or dose reduce until improvement/resolution of symptoms. If managed using Ibr hold, pts can be re-challenged at a lower dose once symptoms improve. If there is recurrence on a lower dose, we recommend observation or consideration or an alternative agent if CLL-directed therapy is still required. Conclusions: In this cohort, A/M was a frequent event and occurred both as an early or late toxicity, though generally developing after 6 months of Ibr therapy. Dose holds and dose adjustments are the most frequent approach to management, and are the most successful. The role of supportive care agents including corticosteroids and CoQ10 is less clear; however not enough data are currently available to suggest efficacy for any single supportive care agent. Further studies are needed to better understand this toxicity and develop best practice management. Disclosures Mato: Celgene: Consultancy; Regeneron: Research Funding; AstraZeneca: Consultancy; Acerta: Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Johnson & Johnson: Consultancy; TG Therapeutics: Consultancy, Research Funding; Prime Oncology: Honoraria; Medscape: Honoraria; Portola: Research Funding. Kennard:AbbVie, Gilead, Verastem: Consultancy. Landsburg:Takeda: Consultancy; Curis: Consultancy, Research Funding. Dwivedy Nasta:Roche: Research Funding; Incyte: Research Funding; Debiopharm: Research Funding; Merck: Other: DSMC; Celgene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Takeda/Millenium: Research Funding; Rafael/WF: Research Funding; Aileron: Research Funding. Svoboda:Kyowa: Consultancy; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Regeneron: Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; TG Therapeutics: Research Funding; KITE: Consultancy. Schuster:Dava Oncology: Consultancy, Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Research Funding.

Description: BACKGROUND: Targeted B-cell receptor signaling pathway inhibitors have changed the treatment landscape of chronic lymphocytic leukemia (CLL); however, treatment decisions remain challenging due to emergence of therapeutic resistance and uncertainties regarding optimal sequencing of therapies. Clinical trials have focused on single treatment options and reported limited outcome data. With increasing options for CLL treatment, research on how to best sequence CLL treatments is needed to optimize patient outcomes. METHODS: The CLL Collaborative Study of Real-World Evidence (CORE) study is a retrospective, multicenter, international, collaborative observational study of patients (pts) with CLL treated at either community or academic sites. For this analysis, pts were randomly selected and eligible for inclusion if they started 1st-line CLL therapy from January 1st, 2012 through present. Demographics, clinical characteristics, treatment patterns, and progression-free survival (PFS) were evaluated. The reason(s) for discontinuing 1st-line and initiating 2nd-line therapy were collected; multiple reasons could be selected. For this analysis, pts were grouped according to whether they received novel agent-based therapy (eg, ibrutinib, idelalisib, venetoclax) or chemotherapy/chemoimmunotherapy (CT/CIT) as 1st-line treatment. RESULTS: Of 351 pts studied, 179 received CT/CIT and 172 received novel agents as 1st-line therapy. Patient data, stratified by 1st-line therapy (CT/CIT vs. novel agents), are shown in Table 1. Most pts were treated in community settings (81%). The median ages were 62 and 66 years for pts receiving CT/CIT and novel agents, respectively. Demographics were generally similar between CT/CIT and novel agent groups with one exception: 17p deletion/TP53 mutations were present in 20% who received novel agents, compared to only 4% who received CT/CIT (p 80% of pts received a novel agent-based therapy as 2nd-line treatment. CONCLUSIONS: In this study, pts with CLL treated since 2012 with CT/CIT or novel agent-based therapies (87% ibrutinib-based) in 1st-line had similar demographics; notably, more pts with 17p deletion/TP53 mutation were treated with novel agents. Although treatment failure was the primary reason for initiating 2nd-line therapy, many pts discontinued novel agents for other reasons, including adverse events and, unexpectedly, completion of therapy. With limited follow-up, in patients largely from community setting, PFS was similar between pts treated with CT/CIT and novel agents; more analyses are necessary to determine whether outcomes are impacted due to discontinuation of treat-to-progression novel agents for reasons other than progression. Overall, novel agents were the 2nd-line therapy of choice, irrespective of 1st-line therapy. These data constitute a first-look at CORE, a long-term study designed to determine how novel therapies and treatment sequencing impacts adverse events and outcomes in the treatment of CLL. Disclosures Mato: TG Therapeutics: Research Funding; Celgene: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; Prime Oncology: Speakers Bureau; AstraZeneca: Consultancy; Acerta: Research Funding; Regeneron: Research Funding; Sunesis: Honoraria, Research Funding; Abbvie: Consultancy; Janssen: Consultancy, Honoraria. Sarraf Yazdy:Bayer: Speakers Bureau. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: 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; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shadman:Abbvie: Consultancy; Pharmacyclics: Research Funding; TG Therapeutics: Research Funding; Beigene: Research Funding; AstraZeneca: Consultancy; Gilead: Research Funding; Mustang: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy; Celgene: Research Funding; Genentech: Consultancy, Research Funding; Acerta: Research Funding; Verastem: Consultancy. Kennard:AbbVie, Gilead, Verastem: Consultancy. Allan:AbbVie: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees. Ujjani:AbbVie: Consultancy, Speakers Bureau. Brander:Novartis: Consultancy, Other: DSMB; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Teva: Consultancy, Honoraria; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding. Nabhan:Cardinal Health: Employment, Equity Ownership. Barr:AbbVie, Gilead: Consultancy. Brown:Abbvie: Consultancy; Verastem: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Sun Pharmaceutical Industries: Research Funding; Invectys: Membership on an entity's Board of Directors or advisory committees; Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Boehringer: Consultancy; Celgene: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Pharmacyclics: Consultancy; Sunesis: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees; Loxo: Consultancy; TG Therapeutics: Consultancy; Genentech: Consultancy; Roche/Genentech: Consultancy. Fox:Roche: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: Travel support, Speakers Bureau; Gilead: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Personal fees and non-financial support, Speakers Bureau; Sunesis: Consultancy. Schuh:Giles, Roche, Janssen, AbbVie: Honoraria. Eyre:AbbVie, Gilead, Janssen: Honoraria, Other: Travel support. Lamanna:AbbVie, Genentech, Gilead, Verastem, Bei-Gene, TG Therapeutics, Acerta: Research Funding; AbbVie, Celgene, Roche-Genentech, Janssen, Pharmacyclics, Gilead, Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Jain:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Infinity: Research Funding; Cellectis: Research Funding; Servier: Research Funding; Pfizer: Research Funding; Adaptive Biotechnologioes: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Genentech: Research Funding; Infinity: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Verastem: Research Funding; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: 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; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Incyte: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Abbvie: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Research Funding; Novimmune: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologioes: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wierda:AbbVie, Inc: Research Funding; Genentech: Research Funding. Skarbnik:Gilead Sciences: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bannerji:AbbVie, Inc.: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy. Samp:AbbVie: Employment, Equity Ownership. Nielsen:AbbVie, Inc: Employment, Equity Ownership. Pauff:AbbVie: Employment, Equity Ownership. Kipps:Celgene: Consultancy; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Genentech Inc: Consultancy, Research Funding. Schuster:Genentech: Honoraria, Research Funding; Dava Oncology: Consultancy, Honoraria; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Research Funding. Follows:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Eichhorst:AbbVie, Celgene, Gilead, Janssen, Mundipharma, Novartis, Roche: Honoraria, Other: Travel support, Research Funding.

Description: Introduction Patients (pts) diagnosed with double hit lymphoma (DHL) are reported to experience poor survival outcomes following first-line treatment with R-CHOP, although survival may be improved with receipt of intensive front-line immunochemotherapy. These results may be altered by selection bias, as prior retrospective series of DHL pts did not report performing routine cytogenetic testing to identify those with DHL. We hypothesized that outcomes might differ for DHL pts identified after the implementation of routine testing at our institution. Methods In January of 2015, our institution began routine testing for MYC-rearrangement (R) by fluorescence in situ hybridization (FISH) for all newly-diagnosed cases of DLBCL and HGBL/BCLU, with reflex testing for BCL2-R and BCL6-R by FISH if positive for MYC-R. Prior to this, FISH for MYC-R, BCL2-R and/or BCL6-R was performed at the discretion of the treating physician or interpreting hematopathologist. Pts included in our analysis were diagnosed with DHL from May 2009 through July 2018. Inclusion criteria were adults treated with first-line curative-intent immunochemotherapy. Exclusion criteria were HIV-associated lymphoma, primary CNS or testicular lymphoma, post-transplant lymphoproliferative disorder, and incomplete clinicopathologic and outcomes data. Primary outcome measures were progression free survival (PFS) and overall survival (OS) in the pre-January 2015 selective testing (ST) and post-January 2015 routine testing (RT) cohorts. Data were censored on 5/31/19. Results Sixty-five pts were included in the analysis. The ST and RT cohorts did not differ significantly on the baseline characteristics of age, sex, stage, performance status, B symptoms, elevated LDH, extranodal disease, stage III/IV, blood or bone marrow involvement, International Prognostic Index score, Ki67, cell of origin, expression of MYC or BCL2 protein or the combination, time from diagnosis to treatment 〉14 days, disease bulk 〉 7.5 cm, transformation from an indolent lymphoma, or front-line treatment with R-CHOP vs intensive immunochemotherapy. Eighty percent (n=52) of pts received intensive front-line immunochemotherapy, most with R-EPOCH (n=42). Median length of follow-up was 32 months (61 months for ST and 24 months for RT). The RT group had a longer 2-year PFS 70% vs 43%, p=0.02; univariate hazard ratio (HR) for progression 2.4, 95% confidence interval (CI) 1.1-5.4, p=0.03, (Figure 1A). The only other variable associated with progression was presence of extranodal disease (HR 2.35, 95% CI 1.0-5.4, p=0.047). In a multivariate model, both ST and the presence of extra-nodal disease were independently associated with progression at 2 years (HR 2.84, 95% CI 1.3-6.4, p=0.012 and HR 2.79, 95% CI 1.2-6.5, p=0.018, respectively). Longer OS was observed with RT (median OS NR vs 16 months, 2-year OS 72% vs 41%, p=0.008; HR 2.97 95% CI 1.3-6.9, p=0.012, Figure 1B). No other factors were associated with longer OS. For pts who relapsed after first-line therapy, survival was poor with a median OS after relapse of 6 and 5 months in the RT and ST groups (p=0.11). When limiting the analysis to only those pts treated with intensive immunochemotherapy, median PFS and OS remained significantly longer for the RT group (2-year PFS 70% vs 38%, p=0.01; median OS NR vs 16 months and 2-year OS 74% vs 38%, p=0.007). Post-relapse survival was similarly poor for those treated with intensive induction regardless of RT vs ST (median post-relapse OS 6 vs 5 months, p=0.1). Conclusions Long-term survival may be improved for DHL pts identified through routine as opposed to selective FISH testing. These data could serve as a new baseline for outcomes of DHL pts identified in this manner. Survival outcomes for our cohort of pts treated with intensive immunochemotherapy are similar to those for DHL pts reported in a recent prospective multicenter study of front-line R-EPOCH (Lancet Haematol. 2018 Dec;5(12):e609-e617). While we suspected that the poorer outcomes experienced by ST pts may have been due to high-risk clinicopathologic factors that contributed to selection bias in testing, this does not seem to be the case for any measured factors. It may be that variation in additional molecular features within this high-risk cytogenetic population could explain differences in survival, and next generation sequencing analysis of DHL patient tissue specimens is planned. Disclosures Dwivedy Nasta: Celgene: Honoraria; ATARA: Research Funding; Pharmacyclics: Research Funding; Rafael: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; 47 (Forty Seven): Research Funding; Millenium/Takeda: Research Funding; Debiopharm: Research Funding; Aileron: Research Funding. Schuster:Merck: Honoraria, Research Funding; Novartis: Honoraria, Patents & Royalties: Combination Therapies of CAR and PD-1 Inhibitors with royalties paid to Novartis, Research Funding; Loxo Oncology: Honoraria; Pharmacyclics: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Nordic Nanovector: Honoraria; AstraZeneca: Honoraria; Pfizer: Honoraria; Acerta: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Chong:Merck: Research Funding; Tessa: Consultancy; Novartis: Consultancy. Rhodes:DAVA Oncology: Honoraria. Landsburg:Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Triphase: Research Funding; Triphase: Research Funding.