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We present long-term combined results of two clinical trials implementing R-MACLO-IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM-MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM-MCL2 ClinicalTrials.gov identifier NCT00878254) received rituximab (375 mg/m2 IV weekly × 4, repeated every 6 months for 3 years). Considering all 44 patients, 41 (93.2%) achieved complete response (CR), two (4.5%) partial response (PR), and one (2.3%) was not evaluated for response. With a median follow up of 7.2 years (range < 1 month to 16 years), the 5-year progression-free survival (PFS) was 55.6% (95% CI: 38.9%-69.4%) and median PFS 7.9 years (95% CI: 3.7-11 years). The 5-year OS was 83.3% (95% CI: 68.1%-91.7%) and median OS was not reached. Patients with blastic variant (n = 6) had a 5-year PFS and OS of 20.8% and 60%, respectively. Myelosuppression was the most common adverse event during immunochemotherapy. Long-term treatment-related mortality was 6.8%. Note, R-MACLO-IVAM followed by maintenance therapy is an effective regimen to induce long-term remission in MCL without need for consolidation with ASCT.

Pulmonary marginal zone lymphoma (PMZL) is the most common non‐Hodgkin lymphoma affecting the lung. PMZL is usually an indolent disease. Clinical and radiological variables associated with shorter survival are largely unknown and no consensus exists on preferred treatment strategy in PMZL. Herein we aimed to identify clinical and radiological features associated with shorter survival and inferior treatment outcomes. Forty patients with PMZL were analyzed. FDG‐avid disease was evident in most patients (93%) with staging PET/CT (n = 15). With a median follow‐up in treated patients (n = 38) of 8.4 years (range 0.07‐18.44), the median progression‐free survival (PFS) and overall survival (OS) were 7.5 years (95% CI 1.8‐9.5) and 15.7 years (95% CI 9.3‐NE) respectively. Shorter PFS was observed in patients who presented at diagnosis with elevated LDH, B symptoms, advanced stage and failed to achieve complete response (CR) after initial treatment. Patients with multifocal lung disease, extrapulmonary MZL and cavitary lesions on CT scans exhibited shorter PFS. Nevertheless, no clinical or radiologic findings were associated with shorter OS. All patients treated with surgery (n = 4) and radiation therapy (n = 3) achieved and remained in CR. No higher grade transformations occurred during the follow‐up period. PMZL exhibited excellent outcomes with a 15‐year PMZL‐related OS of 94.9% (95% CI: 81.25%‐98.7%). Radiation therapy and surgery are potentially curative strategies in localized PMZL., Elevated LDH, B symptoms, advanced stage and failure to achieve complete response after initial treatment are clinical variables associated with shorter progression‐free survival (PFS) in pulmonary marginal zone lymphoma (PMZL). Multifocal lung disease, extrapulmonary MZL and cavitary lesions on computed tomography scans have been identified as radiologic features associated with shorter PFS. Radiation therapy and surgery are potentially curative strategies in PMZL.

Introduction: The SARS-CoV-2 (COVID-19) pandemic continues in the United States, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (“Omicron”) COVID-19 variant wave. Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida from December 1st, 2021 through April 30th, 2022. After categorizing basic demographic factors for individuals whom tested positive for COVID-19 during the study timeframe, we analyzed additional risk factors leading to COVID-19 positivity including, but not limited to, vaccination status, previous COVID-19 positivity, and active receipt of chemotherapeutics. We then analyzed outcomes related to COVID-19, including treatment with advanced COVID-19 therapies such as oral or intravenous antivirals, monoclonal antibodies, convalescent plasma, steroids, or interleukin-6 inhibitors; interactions with inpatient services including emergency department (ED)/urgent care visits, inpatient and/or ICU admissions, and deaths from COVID-19. We finally assessed quality outcomes such as delay in cancer-directed therapy. This study was approved by the University of Miami IRB and Jackson Health System Clinical Trials Office. Results: 498 patients and 18 providers were retrospectively analyzed during the study timeframe. 49 patients tested positive for COVID-19 (9.84%), while 6 providers tested positive (33.3%) (p = 0.015). Patients whom tested positive were 51.0% female (n = 25), 26.5% Black (n = 13), 73.5% Hispanic/Latinx (n = 36), and 2.05% Asian (n = 1). Only 6.12% patients had tested positive for COVID-19 previously (n = 3), and 42.9% were considered unvaccinated (n = 21) while 14.3% were boosted (n = 7). 73.5% (n = 36) presented with symptomatic disease, 46.9% (n = 23) sought care at an ED/urgent care, 32.6% (n = 13) were admitted to the hospital, 6.12% were admitted to the ICU (n = 3), and 16.3% (n = 8) received advanced therapeutics. There were 2 (8.0%) COVID-19-related deaths (and another outside our study timeframe) among 23 non-COVID-19 related deaths in the patient population (p = 0.75). More than half of the patients whom tested positive experienced a cancer treatment delay (n = 27/49; 55.1%). Conclusions: The prevalence of COVID-19 positivity in our patient cohort during the initial Omicron wave mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. COVID-19 positivity conferred appreciable disparities in the presentation of disease as well as receipt of cancer treatment. COVID-19 positivity was more likely to result in symptomatic disease and ED/urgent care visit in cancer patients without previous COVID infection and unvaccinated status. COVID-19 accounted for 8.0% of our clinic’s total mortality. Citation Format: Aliya Khan, Samuel A. Kareff, Priscila Barreto-Coelho, Sunil Iyer, Brian Pico, Michele Stanchina, Giselle Dutcher, José Monteiro de Oliveira Novaes, Aparna Nallagangula, Gilberto Lopes. Prevalence of COVID-19 among hematology/oncology patients and providers of a community-facing county health system during the B1.1.529 (“Omicron”) SARS-CoV-2 variant wave [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B123.

Introduction: Racial and ethnic disparities exist in three areas related to hematopoietic cell transplantation (HCT): donor availability, access, and post-HCT outcomes. A significant barrier to access to HCT for patients (pts) of racial or ethnic minorities (REM) is the limited availability of fully matched donors (i.e., grafts matched at HLA-A, -B, -C, and -DRB1 loci) in volunteer registries. While mismatched unrelated donor (MMUD) grafts (i.e., 0.9). There were no differences in one-year OS (77% vs 74%, p = 0.9) and EFS (63% vs 72%, p = >0.9) between NHW and REM pts. Similarly, rates of acute (17% vs 13%, p = 0.5) and chronic GVHD (5.7% vs 11%, p = 0.5) were comparable between NHW and REM pts. Conclusion: PTCy resulted in encouraging clinical outcomes following MMUD HCT. Post-HCT OS, RFS, and GVHD rates were comparable between NHW and REM pts and those receiving 7/8 or highly mismatched grafts. Favorable post-HCT outcomes following MMUD with PTCy may increase HCT utilization and access for REM pts. Citation Format: Antonio M. Jimenez Jimenez, Sunil Iyer, Krishna Komanduri, Samantha Brown, Trent Wang, Stephanie Chinapen, Denise Pereira, Sean Devlin, Mark Goodman, Amer Beitinjaneh, Craig Sauter, Lazaros Lekakis, Miguel Angel Perales, Doris Ponce, Brian Shaffer. HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplant cyclophosphamide improves clinical outcomes for racial and ethnic minority patients with hematologic malignancies [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B121.

Breast extranodal marginal zone lymphoma (EMZL) is a rare malignancy. We performed the largest published to date single-center retrospective analysis of 13 patients with breast EMZL focusing on clinical characteristics and treatment-related outcomes. The rarity of this disease at our center was concordant with the prevalence reported in the literature, with breast EMZL comprising 2% of 654 MZL cases. Most patients presented with stage I-II disease however four (30.8%) patients had stage IV disease mostly due to occult bone marrow (BM) involvement. Interestingly, EMZL was frequently non-FDG avid (66.7%) on staging PET/CT. With a median follow-up of 3.1 years (range 5 months to 10.2 years), the 3-year progression free survival was 68.7% (95%CI 30.2%-88.9%) and overall survival 80.2% (95%CI 40.3%-94.8%). No patient experienced higher-grade transformation. Herein we show that localized breast EMZL can be effectively treated with radiation therapy providing long term disease control.

Two patients receiving oral etoposide therapy developed Pneumocystis jirovecii pneumonia during chemotherapy with significant lymphopenia without corticosteroid use. In this commentary we discuss cellular mechanisms by which etoposide induced CD4+ T lymphocyte dysfunction and reduced survival may lead to predisposition to P. jirovecii infection.

PURPOSE: Inferior outcomes of Black patients with lung cancer compared with other racial groups are often linked to socioeconomic factors. It is crucial to determine whether a varying prevalence of targetable mutations limits treatments and contributes to disparities. MATERIALS AND METHODS: We conducted a meta-analysis on the prevalence of lung cancer EGFR, ALK, ROS-1, and BRAF mutations in Black patients compared with White, Hispanic, and Asian patients. We searched PubMed/MEDLINE, Cochrane Library, EMBASE, CENTRAL, Google Scholar, and clinicaltrials.gov databases. We selected studies reporting the prevalence of at least one mutation in the Black population. We calculated the pooled prevalence of mutations using fixed effects, exact binomial distributions, and Freeman-Turkey double arcsine transformation to stabilize the variances. RESULTS: Twenty studies with 11,867 patients were included. In Black patients, EGFR was the most prevalent mutation (6%; 95% CI, 5 to 7), followed by BRAF (1%; 95% CI, 0 to 2), ALK (1%; 95% CI, 0 to 2), and ROS-1 (0%; 95% CI, 0 to 1). Black patients had a lower prevalence of EGFR mutations than White, Hispanic, and Asian patients ( P < .01). BRAF mutations were less prevalent in Black compared with White patients ( P < .05), and ALK mutations were less prevalent when compared with Hispanic patients ( P < .05). CONCLUSION: EGFR is the most frequent mutation found in Black patients, although its prevalence is lower than that in other races. Black patients have a low overall prevalence of ALK, ROS-1, and BRAF mutations. Given that disproportional eligibility for targeted therapies may be contributing to inferior outcomes, research focused on the Black population is needed to evaluate specific tumor characteristics and therapeutic strategies.

Background Delayed subdural fluid collections can occur after Ommaya reservoir placement and can cause neurological symptoms and interfere with treatment. We performed a retrospective chart review in order to study risk factors for delayed subdural fluid collections and clinical outcomes. Methods Retrospective chart review was performed for patients undergoing ommaya reservoir placement between 2010-2019 at our institution. Results Out of 53 patients who had Ommaya reservoir placement during the study period, 11 developed delayed subdural fluid collections (21%). HIV infection was the only statistically significant risk factor (p=0.001, Fisher exact test). Thrombocytopenia, ventricle size, use of the reservoir, and suboptimal catheter placement were not associated with development of delayed subdural fluid collections. 2 patients, both HIV positive, required surgical evacuation. Conclusions Delayed subdural fluid collections occur in a significant minority of patients after Ommaya reservoir placement, and some patients require surgical intervention. HIV infection is associated with a higher risk of development of delayed subdural fluid collections. This patient subpopulation may benefit from closer monitoring or adjustment of management protocols.

Combined checkpoint inhibition therapy targeting the programmed cell death 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 pathways has been a successful approach in the treatment of metastatic melanoma, leading to its investigation in the treatment of head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression. Despite the potential for excellent responses, an increased rate of autoimmune neurological toxicity and paraneoplastic conditions has been observed when using these treatment modalities. We present the case of a patient with metastatic HNSCC treated with combination ipilimumab/nivolumab who experienced severe cerebellar ataxia with a positive screen for the anti-Zic4 antibody. This is the first case, to our knowledge, of anti-Zic4 antibody-mediated cerebellar toxicity reported in association with HNSCC. Although the patient experienced an impressive partial response with dual checkpoint inhibition, he suffered grade 4 neurotoxicity. Despite exciting advances in cancer immunotherapy, clinicians must be aware of the rare, debilitating and possibly previously undescribed paraneoplastic and autoimmune toxicities that may occur.

Background The most common subtype of B-cell lymphomas presenting in the conjunctiva is extranodal marginal zone lymphoma (EMZL), accounting for ~80% of cases. Most patients (pts) present with localized disease, and radiation therapy (RT) is the preferred treatment strategy. We aimed to retrospectively analyze our single-institution experience to provide further insight into the characteristics and long-term outcomes of conjunctival EMZL. Methods We evaluated 72 pts diagnosed with conjunctival EMZL between 01/1995 and 12/2020 at the University of Miami. Pts' characteristics included age, sex, TNM-AJCC ocular lymphoma and Ann Arbor staging systems, MALT-IPI score, treatment (RT, chemotherapy, rituximab), and treatment response (complete response (CR), partial response, stable disease, progression of disease). Primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meier method, and compared using the log rank test and the univariable Cox regression analysis. We also performed a competing risk univariable analysis (UVA) assessing predictors of cumulative incidence of relapse/progression, with death without relapse as a competing risk, using the Fine and Gray regression analysis. Results Among all 72 pts, mean age was 59.9 yrs (7-93) with 38 (52.8%) being >60 yrs old, 46 (63.9%) were female, 56 (77.8%) had unilateral conjunctival disease, localized disease (T1N0M0 and Ann Arbor stage I) was present in 63 (87.5%), 6 (8.3%) had disseminated disease with more than 1 extranodal site involved, and 29 (40.3%) had a MALT-IPI of 1 or 2. After biopsy and surgical removal, 65 (90.2%) received additional treatment, while 6 (8.3%) were followed only, and in one case therapy information was not available . RT was the most common treatment (53 pts [73.6%], with 46 [86.8%] of those treated with ≥ 30 Gy). In two of these patients RT was combined with chemotherapy. Other treated pts received immunochemotherapy (12 [16.7%], including rituximab in 8). Five pts with stage II-IV disease received systemic therapy. CR was achieved in 63 (87.5%) after first line treatment, and no high-grade lymphoma transformation was seen. With a median follow up of 6.67 yrs (0.56-24.13), there were 14 relapses (19.4%). Among 53 pts treated with RT there were 8 relapses (15.1%), only one (1.9%) within the RT field. There were 23 progression events (31.9%, 14 relapses and 9 deaths without documented relapse), and a total of 14 deaths (19.4%). Mean PFS and OS were 6.69 yrs (0.49-20.37, SD 4.95) and 7.81 yrs (0.56-24.13, SD 5.40), respectively. The 10-yr PFS and OS were 68.4% (95%CI 52.8, 79.8%) and 89.4% (95%CI 77.4, 95.2%), respectively. Variables associated with shorter PFS in UVA Cox model were age > 60 yrs (HR=2.93, 95%CI 1.08, 7.95; p=0.035), high MALT-IPI (1-2) (HR=2.42, 95%CI 1.01, 5.78; p=0.048), and use of chemotherapy only (HR=2.73, 95%CI 1.13, 6.56; p=0.025). Variables associated with shorter OS included age >60 yrs (HR=9.07, 95%CI 1.17, 70.26; p=0.035) and high MALT-IPI (HR=6.19, 95%CI 1.35, 28.33; p=0.019). CR after frontline therapy was associated with longer PFS (HR=0.13, 95%CI 0.04, 0.45; p=0.001) but not OS. PFS of MALT-IPI 0 vs 1-2 was significantly longer (p=0.042), with 10-yr PFS 80.9% (95%CI 63.4%, 90.6%) vs 55.6% (95%CI 32.1%, 73.8%). Similarly, longer OS was observed in MALT-IPI 0 pts (p=0.0077; 10-yr OS 95.2% [95%CI 82.2%, 98.8%] vs 80.6% [95%CI 55.6%, 92.4%]) (Figure). A subset UVA Cox analysis of patients with Ann Arbor stage I showed longer PFS associated with CR after frontline therapy (HR 0.15, 95%CI 0.04, 0.58; p=0.006) with no significant association with age >60 yrs, high MALT-IPI or use of chemotherapy. Variables associated with shorter OS were age >60 yrs (HR 8.01, 95%CI 1.00, 63.98; p=0.05) and high MALT-IPI (HR 13.41, 95%CI 1.67, 107.99; p=0.015), similarly to the primary analysis. On univariable Fine and Gray regression models with death without relapse/progression as a competing risk, RT (SHR=0.33, 95%CI 0.12, 0.96; p=0.041) and CR-post frontline therapy (SHR=0.11, 95%CI 0.03, 0.36; p Conclusion Patients with conjunctival EMZL exhibit excellent long-term survival, and RT remains the most effective frontline therapy. MALT-IPI appropriately identifies patients at risk for treatment failure. Figure 1 Figure 1. Disclosures Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member. Lossos: Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; NCI: Research Funding; Stanford University: Patents & Royalties; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment.

Introduction A standard therapy for fit older adults (≥60 years) with acute myeloid leukemia (AML) being treated with curative intent consists of induction chemotherapy with cytarabine and an anthracycline followed by 1-4 cycles of shorter course post-remission therapy with cytarabine +/- anthracycline. Historically, HiDAC has been reserved for younger patients due to the high incidence of cytarabine-induced neurotoxicity, febrile neutropenia, and hospital re-admissions in older patients (Mayer et al. 1994). In select older adults (e.g., those with good-risk cytogenetic/molecular abnormalities, or requiring reinduction for persistent AML), the risk/benefit for HiDAC may favor its use. Real world evidence is lacking on the safety of full dose HiDAC (total 18 grams/cycle) in fit older adults in the 60-75 age range. Methods We performed a retrospective analysis of AML patients ≥60 years who received at least one cycle of HiDAC, defined as 3g/m2 every 12 hours for 6 doses, either days 1-3 or days 1, 3, 5, as post-remission therapy or primary re-induction (i.e., after failure of primary induction with 7+3 or CPX-351) between July 1, 2014 and May 28, 2021. AML risk was defined by European LeukemiaNet (ELN) guidelines. All patients had daily neurologic exams including prior to each dose of HiDAC and at the beginning of each nursing shift. The primary endpoint was tolerability, defined as average dose per cycle, rate of dose reductions, incidence of febrile neutropenia, cerebellar toxicity, and rate of hospital re-admissions. Secondary endpoints were overall survival (OS), composite complete remission (CCR) for patients treated with HiDAC re-induction, and duration of relapse-free survival (RFS) (from day 1 of treatment) in all patients. Results From July 2014 to May 2021, 34 patients ≥60-years-old were treated with HiDAC at our center. Median age at HiDAC administration was 64 (60-73) [Table 1]. Approximately half the patients were Hispanic and male and almost all (97%) had ECOG performance scores of 0-1. HiDAC was used as post-remission therapy (following 7+3-type induction in 80%) in 25 patients and as re-induction in 14. Eleven patients (32%) were ELN favorable risk, 8 (25%) were intermediate, and 15 (44%) were poor risk. For post-remission therapy, the average total dose of cytarabine per cycle was 16.6 gm/m2 (6-18 gm/m2) and the median number of cycles was 4 (1-4) [Table 2]; 6 patients (24%) required dose reductions, the most common reason being upcoming allogeneic stem cell transplant (n=4). No cerebellar toxicity was observed. Duration of neutropenia was on average 15 days (7-53) in the re-induction group and 7.5 days (1-29) in the post-remission group, with 23 post-remission patients (92%) receiving granulocyte colony stimulating factors (G-CSF). Eleven hospital readmissions occurred, most commonly (73%) for febrile neutropenia. Early mortality rates were low, with one patient on the post-remission arm and one patient on the re-induction arm dying within 30 and 60 days, respectively, both due to sepsis. Median OS was 15.8 months (95% CI 0-31.8) in patients who received post-remission HiDAC, with 44% of patients still alive with a median follow up of 17.2 months (95% CI 7.2-55.8). Favorable risk patients (n=11) receiving post-remission HiDAC had median OS of 15.8 months (95% CI 0-43.1), while intermediate/poor risk patients (n=14) had median OS of 11.3 months (95% CI 9.3-13.2) [p=0.53]. Median OS was 9.8 months (95% CI 2.5-17.1) in patients who received HiDAC re-induction, with 29% of patients still alive with a median follow up of 28.6 months (95% CI 16.6-39.9) [Table 3]. Five patients (36%) achieved CCR after HiDAC re-induction, all of whom went on to receive post-remission HiDAC. Median RFS was 8.5 months for re-induction and 8.8 months for post-remission patients [Table 3]. Conclusions HiDAC (18 grams) can be safely given to select patients over age 60. Critical to tolerability is rigorous screening of "fitness," limiting the upper age receiving HiDAC to 75, ensuring adequate renal function and euvolemia, and advances in supportive care. Encouraging survival outcomes were observed in older adults receiving post-remission or re-induction HiDAC, independent of ELN risk. Figure 1 Figure 1. Disclosures Bradley: AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Watts: Rafael Pharmaceuticals: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Aptevo Therapeutices: Research Funding.

Introduction Venetoclax in combination with a hypomethylating agent (VEN-HMA) has become a standard of care for older or unfit patients with newly diagnosed AML. Although primarily administered in the outpatient setting, VEN-HMA is associated with significant cytopenias and infectious complications, requiring careful monitoring and dose adjustments. Patients treated with VEN-HMA on clinical trials had a median age of ~75 years. The optimal dose and schedule, safety, and efficacy of VEN-HMA in octo- and nonagenarians is not clearly defined. Methods We performed a retrospective analysis of AML patients ≥80-years-old who received at least 1 day of VEN-HMA at our institution from 11/2018 to 7/2021. Patients with de novo or secondary AML with or without prior HMA or chemotherapy were included. Venetoclax starting dose was 200-400 mg for 14-28 days. Dose adjustments for drug interactions with azole anti-fungals were implemented. HMA was started at 50-75 mg/m2 for 5-7 days of azacitidine or 20mg/m2 for 5 days of decitabine. Dose reduction was defined as any decrease from the starting dose and schedule. Patients who did not complete cycle 1 were included in the overall survival and safety analysis but excluded from response assessment. Results Among 21 patients ≥80-years-old treated with VEN-HMA (20 newly diagnosed, 1 relapsed/refractory), median age was 82 years (range: 80-89) (Table 1), 57% had antecedent MDS, and 38% received HMAs previously. Most patients (81%) were ELN adverse risk, 38% had a complex karyotype, 24% had a TP53 mutation, and 43% had ECOG PS of 2-3. Median overall survival for all patients was 8.0 months (0.5-31.4 months). At time of analysis, 12 patients (57%) were still alive and in remission on VEN-HMA with a median follow-up of 11.5 months (range 2.3-31.4 months). Five patients (24%) died during cycle 1 from sepsis. Of these 5 patients, 4 had a TP53 mutation, 3 had prior MDS, and 3 had received prior therapy for lymphoma. In the remaining 16 patients, median overall survival was 9.9 months (2.3-31.4 months) and the CR/CRh rate was 81% (13/16 patients). Median duration of response was 8.9 months (range 1.0-30.0). Consistent with previous reports, all patients who achieved CR/CRh did so by the end of cycle 2 (median 2 cycles). Most patients also received the standard dose and schedule of VEN (75%) and HMA (57%) during the first cycle. All patients (100%) required venetoclax dose and schedule reduction, with a median final venetoclax dose of 200 mg and duration of 14 days. Average final cycle length was 35 days. Most patients (69%) also required dose reduction of HMA. Median duration of treatment was 7.5 months (range 0.5-31.4). Treatment emergent grade 3-4 anemia occurred in 67% of patients, thrombocytopenia in 81%, and neutropenia in 86%; 17 patients (81%) had treatment emergent febrile neutropenia. There were no infectious deaths in patients who survived cycle 1. The median number of neutropenic fever episodes per patient was 1 (0 to 2). The 4 deaths after cycle 1 were due to progressive disease (n=3) or relapse (n=1). Conclusion VEN-HMA can be safely and effectively given to octogenarians with careful monitoring and dose adjustments. All patients required dose reduction of venetoclax after CR/CRh was achieved, and most also required adjustment of HMA. Despite this, over half of patients achieved durable remissions. The greatest risk of infectious death was in the first cycle, in patients who were heavily pre-treated and enriched for TP53 mutations. When compared to historical controls, outcomes in octogenarians who survive the first cycle appear similar to younger age groups. This work highlights the need for a prospective multi-center effort to optimize the dose and schedule of VEN-HMA in older patient populations. Figure 1 Figure 1. Disclosures Bradley: AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Watts: Rafael Pharmaceuticals: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Aptevo Therapeutices: Research Funding.

INTRODUCTION: Patients with stage I localized extranodal marginal zone lymphoma (EMZL) treated with radiation therapy (RT) have excellent outcomes. Negative bone marrow (BM) biopsy at diagnosis is key to confirm early stage disease. However, BM biopsy is not performed in some patients for various reasons such as comorbidities, patient refusal or physician decision. The aim of this study was to assess the effects of BM status (negative vs. not done) on disease recurrence/progression and survival in EMZL patients presenting with otherwise localized disease by imaging and treated with RT. METHODS: From January 1995 to January 2019, we identified 188 patients with stage I EMZL treated with frontline RT at the University of Miami Health Care System. All patients had biopsy proven EMZL and scans (CT, MRI, and/or PET-CT) at the time of diagnosis. Medical records were reviewed and pertinent information gathered. Relapse/progression was subclassified based on disease location: inside, outside, or inside and outside of the radiation field (RF). The competing risk method and the Gray's test were used in analysis of incidence rates of type of relapse/progression and lymphoma-specific death. The Kaplan-Meier method and the log-rank test were used in analyses of progression-free survival (PFS) and overall survival (OS). RESULTS: Among 188 patients included in this study, 104 (55.3%) were ≤60 years and 135 (71.8%) 60 years (26, 65%). Radiation doses broadly varied but most patients (176, 93.6%) received ≥30 Gy. 183 patients (97.3%) achieved complete response (CR) following RT with 2 (1.1%) achieving partial response (PR), 2 (1.1%) stable disease and 1 (0.5%) demonstrating disease progression. Among 176 patients receiving ≥30 Gy RT, 173 (98.2%) achieved CR. With a median follow-up of 6.2 years (range 0.3-22.3 years) the 10 years-PFS was 64.4% (95%CI:54.9%-72.5%). No difference in PFS was observed by location of disease or BM biopsy (negative vs. not done). Patients treated with ≥30Gy had statistically significantly longer PFS compared to patients treated with There were 23 deaths, 7 attributed to lymphoma. The 10-year OS was 83.3% (95%CI:75.0-89.0%), and there was no difference in OS by EMZL location. Patients without staging BM biopsy had shorter OS (p=0.0062). However, when lymphoma-specific death was analyzed (non-lymphoma death as competing risk) the estimated 10-year cumulative incidence of lymphoma-specific death was 5.3% (2.3%-10.2%) and there was a non-statistically significant difference between patients with and without staging BM biopsy (p=0.5201). The cumulative 10-years incidence of non-lymphoma specific death (lymphoma death as competing risk) was 11.4% (95% CI:6.3%-18.2%). There was a statistically significant difference by BM biopsy status (p=0.0107), with patients without staging BM biopsy having higher incidence of non-lymphoma death compared to negative BM biopsy patients (10-yr rate 26.7% vs 7.9%, respectively), likely due to coexistent comorbidities. CONCLUSION: In this large cohort of patients with stage I EMZL treated with RT we demonstrate for the first time that omission of BM biopsy at diagnosis does not affect lymphoma-specific survival or the incidence of disease relapse/progression overall or by relapse location type, suggesting that diagnostic BM biopsy may not be necessary. Disclosures Alderuccio: Foundation Medicine: Other: Immediate family member; Inovio Pharmaceuticals: Other: Immediate family member; Targeted Oncology: Honoraria; Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; OncLive: Consultancy. Lossos:NIH: Research Funding; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

BACKGROUND: Mantle cell lymphoma is characterized by short remissions and a median overall survival (OS) of less than 6 years with standard chemotherapy. We previously reported results of a single-arm phase II clinical trial of intensive chemotherapy induction with R-MACLO-IVAM followed by thalidomide maintenance with promising progression-free survival (PFS) and OS (Lossos et al. Leuk Lymph 2010). A subsequent single-arm phase II clinical trial assessing rituximab (R) rather than thalidomide maintenance was conducted and preliminary data communicated (Hosein et al. Am J Hematol 2015). We now present the final results of these studies. METHODS: Two prospective single-arm phase II clinical trials conducted at the University of Miami were IRB approved. Eligible patients were chemotherapy-naïve with confirmed diagnosis of MCL using WHO criteria, age 18-75 years, ECOG PS: 0-2, adequate organ function and no history of HIV or prior cancer. Pretreatment staging included CT and PET scans, colonoscopy and bone marrow biopsy. The chemotherapy regimen has been previously described (Lossos et al. Leuk Lymph 2010). Patients who achieved complete responses (both radiologically and pathologically) were eligible for the maintenance phase. Between June 2004 and 2019, 44 patients were enrolled; the first 22 patients received maintenance therapy with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients received R (375mg/m2 IV weekly x 4 weeks, repeated every 6 months for 3 years). OS was calculated from date of diagnosis to date of death or last follow up, and PFS from date of diagnosis to the date of pathological evidence of recurrence or death. Analysis was performed using the Kaplan-Meier method, and the log-rank or Wilcoxon test for group comparison. RESULTS: Median PFS in thalidomide and R cohorts were 7.8 and 8.1 years, and 10-year OS 63.6% and 57.8%, respectively. There was no statistically significant PFS or OS difference between patients treated with thalidomide or R maintenance (Wilcoxon p= 0.988 and p= 0.564, respectively). Therefore, all 44 patients were evaluable together for toxicity and 43 for response. Median age was 58 (range 39-73 years), most patients were males (35, 79.5%) and ECOG PS ≤ 1 (42, 95.5%). All patients had at least stage III disease, with bone marrow involvement in 38 (86.4%), gastrointestinal involvement in 23 out of 39 (59%), and elevated LDH in 14 (68.2%) patients. Ki67 was >30% in 20 (54.1%) and blastic variant in 6 (13.6%) patients. Most patients presented with IPI ≥ 3 (23, 52.3%) and intermediate-high MIPI (30, 68.1%) scores. 36 completed all 4 cycles of therapy, treatment was stopped in 6 after 3 cycles, and in 1 after 2 cycles. 1 patient died during the first cycle. Of the 43 patients completing 2 cycles of chemotherapy 41 (95.3%) achieved complete response (CR) and 2 (4.7%) partial response (PR). There were 23 (52.3%) events for PFS (19 relapses, 4 deaths without documented progression/relapse), and 14 (31.8%) total deaths over a median follow up of 6.7 years (range 1-15). The 5 and 10-year PFS were 54.9% (95%CI: 37.6-69.2%) and 39.2% (95%CI: 22.3-55.8%), respectively; median PFS 8 years (95%CI: 3.9-12.5 years). 5 and 10-year OS were 84.4% (95%CI: 68.4-92.7%) and 60.4% (95%CI: 41.2-75.1%), respectively; and median OS was not reached. PFS and OS were statistically significant shorter in the high-risk MIPI group than intermediate and low groups (5-year PFS rates: 23.1% vs. 53.8% vs. 92.9%, respectively, p CONCLUSIONS: These phase II clinical trials implementing frontline R-MACLO-IVAM in MCL demonstrate high overall response rates (95.3% CR and 4.7% PR) with encouraging PFS and OS. Notably, high risk patients such as those with blastic variant and high-risk MIPI score also demonstrated favorable outcomes compared to historical controls. Results demonstrate that R-MACLO-IVAM is an effective regimen to induce long-term remission and survival in MCL, without need for consolidation with stem-cell transplant. Disclosures Alderuccio: OncLive: Consultancy; Puma Biotechnology: Other: Immediate family member; Agios: Other: Immediate family member; Foundation Medicine: Other: Immediate family member; Inovio Pharmaceuticals: Other: Immediate family member; Targeted Oncology: Honoraria. Alencar:Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Rosenblatt:Mologen AG: Employment; Kite Pharma: Employment; Synergys Technologies: Employment; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Merck: Employment. Lossos:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding.

e13105 Background: Although poorer outcomes of lung cancer in Blacks compared to other racial groups has been strongly linked to socio-economic factors, it is important to investigate whether lower prevalence of targetable mutations limit treatment options, thereby also contributing to worse outcomes. This study examines the prevalence of EGFR, ALK, ROS-1 and BRAF lung cancer mutations in Blacks compared to other races. Methods: We conducted a meta- analysis compliant with PRISMA guidelines. Searched databases included PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Google Scholar and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Searches were run to 11/19/2018. Two rounds of screening were performed based on title and then abstract by two independent reviewers. For the purposes of this study we defined racial groups as Black, Asian, Hispanic, and White/Caucasian. We selected studies of lung cancer patients (any stage or type) where the prevalence of at least one mutation was reported in Blacks. We calculated the pooled prevalence of mutations by racial group using fixed effects, exact binomial distributions and Freeman-Turkey double arcsine transformation to stabilize the variances. Results: Prevalence % of mutations by race reported with 95% Confidence Interval in parentheses N = number of tests performed We included 20 studies which totaled 11,867 lung cancer patients. Each mutation tested on a tissue sample was considered an event, for a total of 15,306 events. EGFR was the most prevalent mutation in Blacks (6%). Compared to other races Blacks had the lowest prevalence of all four mutations. Conclusions: In the era of targeted therapy, outcomes for metastatic lung have improved significantly. Of concern, our results show that Blacks are disproportionately ineligible for these therapies due to lower prevalence of targetable mutations. More research is needed to evaluate the unique tumor characteristics and therapeutic strategies in this sub group of patients, in the hope of achieving better disease outcomes.[Table: see text]

Post-infarction ventricular septal defect (PI-VSD) is a devastating complication that carries a high mortality with or without surgical repair. Percutaneous closure is an attractive alternative in select patients though requires appropriate characterization of the PI-VSD as well as careful device and patient selection. We describe a multidisciplinary and multi-modality imaging approach to successful percutaneous closure of a PI-VSD.

Background: We sought to determine the association between cigarette smoking and carotid plaque ultrasound morphology in a multiethnic cohort. Methods: We analyzed 1,743 stroke-free participants (mean age 65.5 ± 8.9 years; 60% women; 18% white, 63% Hispanic, 19% black; 14% current and 38% former smokers, 48% never smoked) from the Northern Manhattan Study using an ultrasound index of plaque echodensity, the Gray-Scale Median (GSM). Echolucent plaque (low GSM) represents soft plaque and echodense (high GSM) more calcified plaque. The mean GSM weighted by plaque area for each plaque was calculated for those with multiple plaques. Quintiles of GSM were compared to no plaque. Multinomial logistic regression models were used to assess associations of cigarette smoking with GSM, adjusting for demographics and vascular risk factors. Results: Among subjects with carotid plaque (58%), the mean GSM scores for quintiles 1-5 were 48, 72, 90, 105, and 128, respectively. Current smokers had over a two fold increased risk of having GSM in quintile 1 (odds ratio (OR) = 2.17; 95% confidence interval (CI), 1.34-3.52), quintile 2 (OR = 2.33; 95% CI, 1.42-3.83), quintile 4 (OR = 2.05; 95% CI, 1.19-3.51), and quintile 5 (OR = 2.13; 95% CI, 1.27-3.56) but not in quintile 3 (OR = 1.18; 95% CI, 0.67-2.10) as compared to never smokers in fully adjusted models. Former smokers had increased risk in quintile 2 (OR = 1.46; 95% CI, 1.00-2.12), quintile 3 (OR = 1.56; 95% CI, 1.09-2.24), quintile 4 (OR = 1.66; 95% CI, 1.13-2.42), and quintile 5 (OR = 1.73; 95% CI, 1.19-2.51), but not in quintile 1 (OR = 1.05; 95% CI, 0.72-1.55). Conclusions: A nonlinear, V-shaped-like relationship between current cigarette smoking and plaque echodensity was observed. Former smokers were at the highest risk for plaques in high GSM quintiles. Thus, current smokers were more likely to have either soft or calcified plaques and former smokers were at greater risk of having only echodense plaques when compared to those who have never smoked. Further research is needed to determine if plaque morphology mediates an association between smoking and clinical vascular events.

Introduction: Many pathological mechanisms associated with smoking have been described, but studies on cigarette smoking in relation to carotid plaque morphology are lacking. Given that certain plaque compositions are more prone to cause cerebrovascular events, we sought to determine the association of carotid plaque density and cigarette smoking in an urban multi-ethnic cohort. Methods: This cross-sectional study analyzed 1743 stroke-free participants from the population-based Northern Manhattan Study using an ultrasonographic index of plaque echodensity, the Grey Scale Median (GSM). Echolucent plaque (low GSM) is more soft and fibrous, while echodense (high GSM) is more calcified. For individuals with multiple plaques, the mean GSM weighted by plaque area for each plaque was calculated. Quintiles of GSM were calculated among those with plaque and compared to those with no plaque as the reference. We used multinomial logistic regression models to assess the associations of current cigarette smoking with GSM, adjusting for demographics and vascular risk factors. Results: The mean age was 65.5±8.9 years, 60% were women, 18% white, 63% Hispanic, 19% black, 14% current smokers, 38% former smokers, and 48% never smokers. Carotid plaque was present in 58% of subjects. Current smokers were at a two-fold increased risk of being in GSM quintiles 1, 2, 4, and 5 as compared to never smokers (Table). Conclusions: A U-shaped relationship between current cigarette smoking and plaque echodensity is observed. Smoking is associated with both echodense calcified plaque as well as with echolucent, soft plaque that are more prone to rupture. Research is needed to determine if these vulnerable plaque phenotypes may mediate an association between cigarette smoking and clinical vascular events.

Liver transplantation (LT) has not traditionally been offered to patients with intracardiac shunts (ICSs) or pulmonary hypertension (PH). There is a paucity of data regarding cardiac structural characteristics in LT candidates. We examined echocardiographic characteristics and their role in managing LT candidates diagnosed with ICS and PH. We identified 502 consecutive patients (318 men, mean age 55 ± 11 years) who underwent LT and had preoperative echocardiogram. Demographics, cardiovascular risk factors, and echocardiographic variables were recorded and data were analyzed for end-stage liver disease diagnosis. ICSs were diagnosed with contrast echocardiography and PH was defined as estimated pulmonary artery systolic pressure >40 mm Hg. Primary end points included short-term (30-day) and long-term (mean 41-month) mortalities and the correlation between pre- and perioperative stroke. In our studied population >50% had >2 cardiovascular risk factors and with increasing frequency ICSs were diagnosed in 16%, PH in 25%, and intrapulmonary shunts in 41% of LT candidates. There was no correlation between short- and long-term mortality and ICS (p = 0.71 and 0.76, respectively) or PH (p = 0.79 and 0.71). Importantly, in those with ICS, no strokes occurred. In conclusion, structural differences exist between various end-stage liver disease diagnoses. ICSs diagnosed by echocardiography are not associated with an increased risk of perioperative stroke or increased mortality. A diagnosis of mild or moderate PH on baseline echocardiogram is not associated with worse outcomes and requires further assessment. Based on these findings, patients should not be excluded from consideration for LT based solely on the presence of an ICS or PH.

The number of foods available at a meal has been suggested as a major determinant of the amount consumed. Two studies conducted in humans test this idea by altering the number of foods available at a meal where participants eat the available foods ad libitum. In Study 1, dinner intake of twenty-seven young adults was measured. The amount consumed was measured when subjects were served either: (a) a composite meal (a protein rich food, a carbohydrate rich food, and a vegetable), (b) a low carbohydrate meal (protein rich food and vegetable), or (c) a vegetarian meal (carbohydrate rich food and vegetable). In Study 2, twenty-four subjects were given two different meals presented either as individual foods or as a composite meal (stir-fry or stew). Both studies show that the greater the number of foods offered at a meal, the greater the total intake. Study 2 demonstrated that the effects observed in Study 1 could not be attributed to different nutrient compositions, but was rather due to the presentation of the individual foods because the same foods that were offered as individual foods were combined to make the composite meal. The results demonstrate that the greater the number of foods offered at a meal, the greater the spontaneous intake of those foods. This finding is important because not only does it expand the concept of variety from the kinds of foods to the number of foods, but it presents an environmental variable that might contribute to overeating and obesity.