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Patients with double- and triple-hit lymphomas (DHL/THL) have inferior outcomes with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and higher-intensity regimens such as dose-adjusted (DA)-EPOCH-R are standard. Dose-intensification of DA-EPOCH-R is guided by hematologic toxicity, without conclusive benefit for DHL/THL patients. To determine if cumulative doses of DA-EPOCH-R or compliance with dose adjustment impacts survival, we retrospectively evaluated detailed clinical data from 109 adult (age ≥18 years) patients with DHL/THL treated with ≥4 cycles of induction DA-EPOCH-R from 2014 to 2019 at six centers. A comprehensive multivariate analysis was performed. Survival outcomes for the entire cohort were comparable to historical estimates for DHL/THL treated with this regimen (median follow-up 27.9 months). Overall survival (OS) and progression-free survival (PFS) were not significantly associated with cumulative chemotherapy dose, dose escalation, or compliance with dose adjustment. Heterogeneous dosing practices were observed. Prospective investigation is warranted to evaluate the practice of dose adjustment of R-EPOCH for patients with DHL/THL.

Venetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution. Thirty-three untreated AML patients unfit or unwilling to receive induction chemotherapy and prescribed venetoclax/azacitidine off-trial were retrospectively analyzed and compared with 33 patients who received the same therapy on trial. Outcomes were compared, and comparisons were made to a theoretical scenario in which off-trial patients received induction. Digital droplet polymerase chain reaction evaluated measurable residual disease (MRD). Off-trial venetoclax was attainable in nearly all patients for whom this was desired. The complete remission (CR)/CR with incomplete blood count recovery rate was 63.3% for off-trial patients who received treatment and 84.9% for trial patients (P = .081). The median overall survival for off-trial patients who received treatment was 381 days (95% confidence interval [CI], 174, not reached) vs 880 days (95% CI, 384, not reached) for trial patients (P = .041). Prior exposure to hypomethylating agents was associated with worse outcomes. Response rates with venetoclax/azacitidine were not inferior to a theoretical scenario in which patients received induction, and early death rates were less than expected with induction. MRD negativity was achievable. Newly diagnosed AML patients treated in a “real-world” scenario with off-trial venetoclax/azacitidine had inferior outcomes compared with patients treated in the setting of a clinical trial. Additionally, this therapy may be as effective, and less toxic, when compared with induction chemotherapy.

In this paper, I explore how contemporary musicians using electronic technologies in improvised music conceptualize skill and virtuosity in their musical practices. This includes ideas about the role and agency of technology, learned and repeatable physical skill, skill acquisition, skill transmission, and the projection of learned skill from traditional instruments onto new instruments. The musicians’ use of idiosyncratic and individually constructed instruments—instruments with little or no history of a performance practice—makes this field a rich resource to examine how such conceptions are developed. Among the musicians I interviewed, the relationship between physical skill and virtuosity is particularly contested. While they frequently value such skill, they also connect it to perceived excesses of certain factions within Western art music, jazz, and other established musical performance practices where physical skill can be conflated with (or considered as the primary element of) musical skill, writ large. This perception of the excess and the prioritization of physical skill have led some interviewed musicians to adopt antivirtuosity as a reactive counter-ideology or to explore the less tangible concepts of hearing, creativity, imagination, memory, novelty, innovation, and even ideas of management as constitutive of musical virtuosity and skill. This paper is part of a larger ethnographic examination of a diverse cross-section of contemporary musicians who improvise with new, repurposed, and reinvented electronic technologies, including Robert Henke (one of the original authors of the software package Ableton Live), guitarist Nels Cline (Wilco), composer and flute player Anne La Berge, and trumpeter/composer Wadada Leo Smith.

BACKGROUND: Central nervous system (CNS) relapse in systemic non-Hodgkin's lymphoma is associated with a guarded prognosis with a median survival of only 2-6 months. However, information regarding CNS relapse is still limited and there is no consensus regarding which clinical or biologic risk factors should be used to identify patients who need prophylaxis and the optimal prophylactic regimen has not yet been established. The CNS-IPI score represents a robust risk model for CNS relapse in patients with diffuse large B cell lymphoma treated with R-CHOP and may potentially serve as a useful benchmark to evaluate the impact of novel treatment approaches. In particular, patients with chromosomal rearrangements of MYC and BCL2 and/or BCL6 genes, as is encountered in double hit (DHL) or triple hit (THL) lymphoma, have been associated with an increased risk for CNS involvement in retrospective series. CNS prophylaxis is typically administered in patients with DHL/THL treated with DA-R-EPOCH due to this perceived heightened risk, but there are limited data to support this approach. METHODS: We conducted a comprehensive multi-institutional retrospective analysis of outcomes of patients with DHL/THL, who received a minimum of 4 cycles of DA-R-EPOCH therapy with or without CNS prophylaxis, namely intrathecal (IT) or high-dose intravenous (IV) methotrexate or cytarabine. Each academic institution provided clinical data to assess the risk of CNS relapse (CNS-IPI) and FISH testing for MYC/BCL2/BCL6 translocations. Outcomes included overall survival (OS), progression-free survival (PFS), CNS relapse-free survival (CNSFS) and time to CNS recurrence which were calculated from time of diagnosis. Fisher's exact test or Chi-square test and Kaplan-Meier method were used to evaluate associations between outcomes and demographics as well as clinical characteristics including administration of CNS prophylaxis and CNS-IPI risk stratification. RESULTS: We collected data on 109 DHL/THL patients across 6 US academic medical centers. Demographic and clinical variables at diagnosis include - Age >60 57.8%(n=63); Male sex 59.6%(n=65); Stage III/IV 78.9%(n=86); ECOG PS >1 12.8%(n=14); CNS-IPI low risk (score 0-1) 11%(n=12), intermediate risk (score 2-3) 57.8%(n=63), high risk (score 4-5) 31.2%(n=34). A total of 95 (87.2%) patients received CNS prophylaxis [IT 81.1%(n=77); IV ± IT 18.9%(n=18)] with a median of 4 doses. Eight patients developed CNS relapse (7.3%) during a median of 25.9 (range 4.0 to 63.2) months of follow up. The patterns of relapse were predominantly leptomeningeal (n=7/8), as shown in Table 1. Estimated incidence was 4.9% at 12 months and 6.1% at 24 months after diagnosis. 5.6% (1/18) of the patients who received IV ±IT CNS prophylaxis developed CNS relapse, whereas the rates of CNS recurrence for patients who received only IT or no CNS prophylaxis were 6.5% and 7.1% respectively. No statistically significant differences in outcomes were found between baseline patient characteristics with respect to whether or not CNS prophylaxis was received, as well as the route of administration of CNS prophylaxis. The rate of CNS relapse was low for patients with low to intermediate compared to high CNS-IPI scores (4.0% vs. 14.7%, p=0.047). Patients with high CNS-IPI scores had reduced CNSFS (2-yr survival: 85.2% vs 97.3%, p=0.08), as well as reduced OS (2-yr survival: 46.5% vs. 87.5%, p CONCLUSIONS: CNS relapse is associated with significantly reduced OS as compared to systemic non-CNS relapse following R-EPOCH treatment in DHL/THL, justifying the need for a rational CNS prophylaxis strategy in these patients. The rate of CNS relapse was significantly lower in patients in the low-intermediate CNS-IPI risk category but it is unclear whether CNS events are reduced by administration of IT CNS prophylaxis due to the relatively small proportion of DHL/THL patients who did not receive any CNS prophylaxis. Furthermore, only 1 of the 18 DHL/THL patients (including 6 patients with high CNS-IPI scores) who received IV ± IT CNS prophylaxis developed CNS relapse, suggesting that this prophylactic strategy, especially in patients with high risk CNS-IPI scores, may be more effective in preventing this devastating clinical event. Disclosures Haverkos: Viracta THerapeutics: Consultancy. Hughes:Acerta Pharma and HOPA: Research Funding; AstraZeneca: Consultancy; Genzyme: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Grover:Genentech: Research Funding; Tessa: Consultancy. Portell:AbbVie: Research Funding; Amgen: Consultancy; Bayer: Consultancy; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy. Voorhees:AstraZeneca: Research Funding. Landsburg:Triphase: Research Funding; Seattle Genetics: Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Kamdar:BMS: Consultancy; Seattle Genetics: Speakers Bureau; Pharmacyclics: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy. Kahl:Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Hill:Genentech: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding.

e19507 Background: Studies evaluating VEN with hypomethylating agents in AML patients have reported no incidence of clinical TLS. However, little is known about TLS development in a real-world setting. Here, we investigate our institutional incidence of clinical TLS and describe these patients’ presentations. Methods: This is a single-center, retrospective study of 156 adult pts treated with AZA/VEN for AML between 2015-2019. The primary outcome is the absolute incidence of clinical TLS after AZA/VEN administration per Cairo-Bishop (CB) criteria. Secondary outcomes include median time to TLS, CTCAE grade of TLS, and mortality. All patients received TLS mitigation strategies including fluids, uric acid lowering agents, and frequent lab monitoring. VEN was escalated over 3-4 days, starting at 100 mg, and given with AZA at the standard dose and schedule. Results: The median age was 70 years (22-89); 80 pts (51%) were female. 121 pts (78%) were treatment-naïve, 26 pts (17%) were relapsed, and 9 pts (6%) were refractory. Four pts (3%) developed clinical TLS per CB criteria after AZA/VEN administration. Two pts were relapsed, one pt was treatment-naïve, and one pt had mixed phenotype acute leukemia, B/myeloid. All four pts developed renal insufficiency. No seizures, cardiac arrhythmias, or mortality occurred secondary to TLS. Two pts required renal replacement therapy, and two pts required escalation of care to ICU for TLS management. Median time to TLS onset was 12 hours (10-25) after receiving the first dose of VEN. CTCAE grade 3 TLS occurred in 2 pts (1%) and grade 4 TLS occurred in 2 pts (1%). VEN was held in 2 pts (8, 10 days); no pts required permanent discontinuation of VEN. Baseline features for each patient are listed in the table. Conclusions: Though we report higher rates of clinical TLS compared to prior studies, the incidence of clinical TLS with AZA/VEN remains low. These results support close monitoring of pts, particularly in the first 24 hours of receiving VEN. [Table: see text]

Background: Cytomegalovirus (CMV) infection remains an important cause of morbidity and cost following umbilical cord blood transplantation (UCBT). While the introduction of letermovir represents a novel approach to CMV prophylaxis, optimal CMV management strategies remain controversial. An intensive strategy to prevent CMV disease including one week of pre-transplant ganciclovir followed by high-dose acyclovir or high-dose valacyclovir through day 100 reduced post-transplant CMV reactivation (Milano et al, Blood 2011), but this approach is costly and potentially challenging to administer. Insurance approval for outpatient high-dose valacyclovir is variable, and the pill burden of high-dose acyclovir for post-transplant patients may be unmanageable. A recent study demonstrates that the removal of pre-transplant ganciclovir does not decrease CMV reactivation rates (Hill et al, BBMT 2018). At our center we have attempted to implement the high intensity strategy described above, but for patients who are unable to obtain high-dose valacyclovir at hospital discharge, we have transitioned to standard dose 800 mg acyclovir twice daily. Additionally, in November 2016, we discontinued pre-transplant ganciclovir. To examine the efficacy of these approaches, we compared CMV outcomes among these patients. Methods: All consecutive adult CMV seropositive (CMV R+) patients who received their first double UCBT from December 2009 to January 2018 were reviewed. Patients were excluded if they had initial CMV reactivation prior to day 0 or after day 100, graft failure, death or relapse before day 100, or participated in a CMV prophylaxis trial. Starting the day of transplant, CMV R+ patients received either valacyclovir 2 grams orally 3 times daily or acyclovir 500 mg/m2 intravenously every 8 hours until able to tolerate oral medication. At hospital discharge, patients for whom valacyclovir was authorized by insurance received valacyclovir 2 grams orally 3 times daily through day 100. All others received acyclovir 800 mg orally twice a day through day 100. No patients received anti-thymocyte globulin with conditioning. All patients transplanted prior to November 2016 received pre-transplant ganciclovir, after which pre-transplant ganciclovir was discontinued. CMV reactivation was defined as any detectable PCR positive whole blood sample (checked twice weekly through day 100). Thresholds for treatment with ganciclovir or foscarnet evolved over time, but required high initial copies levels, persistent or rising DNAemia, or evidence of end-organ involvement. Acute graft-versus-host-disease (aGVHD) treatment was based on institutional guidelines and uniform for all patients. Results: Demographics of the 101 patients studied are provided in table 1. Forty-one patients received prophylaxis with high-dose valacyclovir until post-transplant discharge only (median 23 days) and 60 received valacyclovir through day 100. Between day 0 and day 100, fewer patients in the high-dose valacyclovir group (n= 20, 36%) had CMV reactivation compared to those in the acyclovir group (n= 23, 57%), p= 0.025 (figure 1). Nine patients (9%) in the acyclovir group and 6 (6%) in valacyclovir group received CMV directed treatment (p= 0.1). Patients who did or did not received pre-transplant ganciclovir had similar rates of CMV reactivation (p= 0.55 in acyclovir arm, p= 0.15 in valacylcovir arm). Overall survival (p= 0.64), neutrophil and platelet engraftment time, and incidence of grade 2-3 (p= 0.7) and grade 3-4 aGVHD (p= 0.3) were comparable between groups. Conclusions: High-dose valacyclovir through day 100 post-transplant as compared to through the day of hospital discharge post-transplant reduced CMV reactivation rates. While threshold for treatment will vary according to institutional protocol, high-dose valacyclovir through day 100 likely reduces treatment episodes. One week of pre-transplant ganciclovir does not reduce CMV reactivation rates. These data provide important baselines for future comparisons of outcomes following letermovir prophylaxis in this population. Disclosures Haverkos: Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Abstract 3404 Poster Board III-292 Long-term survival and disease control following autotransplant have been known to be poor in symptomatic MM patients who were in relapse prior to transplant, had adverse cytogenetic abnormalities (CA) or high LDH (> 190 IU/mL) at diagnosis. In the study, we sought to improve the outcome of these patients by combining bortezomib with standard high-dose melphalan for autotransplant and implementing 3-year post-transplant maintenance with bortezomib, lenalidomide and dexamethasone. Between September 2006 and March 2009, 34 patients (median age 62, range 38 to 77 years) were accrued to the sequential regimens of 1) tandem autotransplant prepared by the MVD of ‘melphalan 200 mg/m2 (D-1) + bortezomib 1.3 mg/m2 × 2 (D-4, D-1) + dexamethasone 20 mg x 4 (D-4 through D-1)’; 2) the VLD of ‘bortezomib 1.3 mg/m2/day x 4 (D1, 4, 8, 11) + lenalidomide 10 mg/day x 14 (D1 through 14) + dexamethasone 20 mg/day x 4 (D1, 4, 8, 11)’ q 3 months for 2 years; 3) the LD of ‘monthly lenalidomide 10 mg/day x 14 + dexamethasone 20 mg q Monday in between of the VLD for the first 2 years, followed by a monthly course for the 3rd year. Of the 34 patients, 11 (32%) had unfavorable CA, 15 (44%) high LDH and 10 (29%) prior relapse. 16 patients (47%) had immunoglobulin (Ig) G, 10 (29%) Ig A, 6 (18%) light chain only and 2 (6%) nonsecretory MM. 14 patients (41%) received tandem transplant and 20 (59%) single transplant due to insurance reasons. 32 patients (94%) were able to maintain the treatment until the last follow-up on August 15, 2009 or until relapse or death. 19 patients achieved either a stringent complete remission (s-CR) (n = 16) or CR (n = 3), with an 1-year cumulative incidence (CI) of 46%. 2 additional patients achieved CR following the 2nd transplant. During the maintenance, 3 additional patients achieved s-CR (N = 1) or CR (n = 2), resulting in 71% of the 18-mo CI of response > CR. By the landmark analysis at the time of transplant, the estimated 3-year Kaplan-Meier survival, CI of relapse and event free survival (EFS) are 96% with 2 deaths (1 of MM, 1 of pulmonary embolism), 15% with 5 relapses and 70% with 6 events, respectively. Presence of CA impacted adversely the EFS: 61% of patients without CA vs. 39% of those with CA (Logrank p = 0.06). However, a history of prior relapse or high LDH was not associated with inferior EFS: 42% with prior relapse vs. 76% without prior relapse (p = 0.27); 45% with high LDH vs. 51% with normal LDH (p = 0.86). Although the current findings are limited by the small number of patients and the short duration of follow-up, the data suggests that additional bortezomib to the standard high-dose melphalan and implementation of long-term maintenance post-transplant with bortezomib and lenalidomide may overcome the adverse factors in high-risk MM patients for relapse. Further study is necessary to confirm the findings. Disclosures: Myint: Seattle Genetics, Inc.: Research Funding.