ALBERT

Description: Introduction Studies of EBV positive (+) and negative (-) classical Hodgkin lymphoma (cHL) have shown the importance of the immune microenvironment in affecting Reed-Sternberg (hRS) cell survival, proliferation, and biologic behavior. For example, macrophage infiltrates may correlate with inferior disease outcome and survival and proliferation of the hRS cells depends on trophic signals from various inflammatory cells, including CD4+ T cells. The latter finding may explain why HIV-cHL patients (pts) usually present with higher circulating CD4+ T-cell counts (cCD4) compared to HIV-related non-Hodgkin lymphoma. Pathobiologically, HIV-cHL differs from HIV negative cHL (cHL) in that it is nearly always EBV+, has higher numbers of hRS cells, presents with more advanced median stage, exhibits more commonly the mixed cellularity (MC) pattern, and some studies suggest it is more clinically aggressive. To investigate the microenvironment of HIV-cHL and its influence on cHL biology, we assessed the immune cell composition and clinical characteristics of HIV-cHL and compared the findings to those of EBV+ and EBV- cHLs. Methods 31 HIV-cHL and 40 cHL (8 EBV+/32 EBV-) cases were identified and corresponding tissue microarrays (TMAs) created. TMAs were evaluated for EBV (EBER), CD30, and microenvironment-associated antigens: PAX5, CD3, CD4, CD8, CD68, CD163 (% positive), TIA1, FOXP3 (relative number 0-4+); the hRS-macrophage microenvironment was evaluated by assessing the number of hRS where 〉50% of the circumference of the neoplastic cell was associated with CD68+ cells. Results were compared based on HIV status, EBV status (in HIV negative pts), demographics, cCD4 and histology; each was correlated with overall survival. Analyses were performed using non-parametric Fisher's exact test, Kaplan-Meier method and Cox Proportional Hazards model. Results M:F ratio was 9:1 in the HIV group vs. 1.3:1 in the HIV negative pts (p

Description: Introduction: EPOCH-based chemotherapy is considered a preferred first-line treatment for HIV-associated diffuse large B-cell lymphoma (DLBCL) and primary effusion lymphoma in the 2019 NCCN guidelines. We previously reported that adding the HDAC inhibitor vorinostat (VOR) to EPOCH had no impact on complete response (CR) rate, the primary trial endpoint, and similar 1-year survival rates (ASCO 2018, abstract 7573). Here, we report updated results from AMC075 and evaluate the impact of a DTI ≥15 days on clinical outcomes. A DTI ≥15 days has been shown to be associated with a better prognosis in an HIV-negative population treated with R-CHOP (Maurer et al. J Clin Oncol 2018; 36:1603-1610). We also look at the impact of allowing 1 cycle of systemic therapy given prior to study enrollment in order to circumvent logistical challenges in recruiting otherwise eligible trial subjects. Methods: Between 2012 and 2017 we conducted a randomized phase II study of EPOCH (with rituximab in CD20+ tumors) ± VOR 300 mg administered on days 1-5 of each cycle with HIV antiretroviral therapy in 90 participants with aggressive HIV-NHLs. Eligible patients had at least one of the following high-risk features or tumor characteristics: Age-adjusted International Prognostic Index (aa-IPI) of 2-3, Ki-67 ≥ 80%; activated B-cell (ABC) diffuse large B-cell lymphoma(DLBCL); or any other aggressive non-germinal center (non-GCB), non-Burkitt B-cell NHL. Patients who received 1 prior cycle of chemotherapy (CHOP-like or EPOCH) +/- rituximab were allowed to register. The primary endpoint was CR rate. Secondary objectives included determining adverse events, survival rates, and the effect of EPOCH +/- VOR on HIV viral reservoirs. We performed a post-hoc analysis evaluating the impact of time from DTI ≥15 days vs. 200 cells/mm3(Table 1). The 3-year overall survival rates for VOR-EPOCH was 70% and for EPOCH 77% (log-rank P=0.39), and 3-year event-free survival rates were 63% vs. 69%, respectively (log-rank P=0.32) [Figure 1]. Thirty-six patients (86% of n=42) with long DTI (≥15 days) had CR, compared to only 25 (57% of n=44) with short (

Description: Abstract 1779 Introduction: Tumor Lysis Syndrome (TLS) is an oncologic emergency that leads to a host of metabolic disturbances which can ultimately result in acute renal failure and death. Currently rasburicase, Elitek™, is FDA approved for the treatment of TLS in patients with leukemia, lymphoma, and solid tumor malignancies which have risk factors for TLS. The approved adult dose is 0.2mg/kg/day over 30 minutes for up to 5 days. Chemotherapy should be initiated within 24 hours of rasburicase administration. Since rasburicase's introduction to the market, various studies have examined single dose use (3mg and 6mg) in the adult population, trying to resolve the dilemma of determining a dosing regimen for adults that is as effective as the FDA approved dosing regimen, while minimizing cost. This study was aimed at determining if a single 4.5mg dose of rasburicase would be adequate in reducing uric acid levels (UAL) as compared to the FDA approved conventional weight based approach; it also sought to determine the cost-effectiveness of this approach. Method: This is a retrospective study of the John H. Stroger Jr. Hospital of Cook County (JHS) patients who were administered a single dose of 4.5 mg rasburicase for TLS from 12/2007 to 06/2010. We included patients ≥ 18 years old, with a hematologic malignancy and on chemotherapy or about to start receiving chemotherapy within 24 hours of rasburicase administration. Patients with low risk for TLS or an indication other than prevention and management of TLS were excluded. Result: Demographics: Characteristics: Responders are defined as patients that achieved more than 50% reduction in the UAL at 24 hours, 48 hours or 96 hours or a decrease of UAL to normal levels. Two patients required a second dose to achieve response. The non-responders did not receive any additional doses for unclear reasons. No adverse events were noted. Conclusion: This retrospective study provides evidence that a single 4.5mg dose of rasburicase effectively reduced plasma UAL to within normal limits. In addition, decrease in plasma UAL was observed within 24 hours after administration. No effect on electrolytes and serum creatinine was noted. The cost-effectiveness of a single 4.5mg dose of rasburicase was evaluated based on dose and drug cost. The potential cost saving was substantial when compared with the FDA approved dose. In our opinion, this study validates the use of a single dose of 4.5mg rasburicase in the treatment and prophylaxis of TLS. This dose can be considered as a possible alternative to the FDA approved adult dosing regimen. Disclosures: No relevant conflicts of interest to declare.

Description: EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count

Description: Introduction: Patients (pts) infected with HIV have a 6-8 fold increased risk of classic Hodgkin lymphoma (cHL). Incidence may have increased with the implementation of combined anti-retroviral therapy (cART) in the mid 1990s. Frontline therapy for HIV-associated cHL (HIV-cHL) using, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in the pre-cART era showed a 2 year overall survival (OS) of 48%, but outcomes are currently similar to the non-HIV population. Pts with advanced disease have a 30% chance of relapse with ABVD. Brentuximab vedotin (BV), an anti-CD30 an antibody drug conjugate that selectively induces apoptosis of CD30+ cells with a complete response of 34% in patients with relapsed/refractory cHL. An international trial of BV with doxorubicin, vinblastine, and dacarbazine (AVD) vs. ABVD is ongoing. Here we present the phase I portion of the first trial using BV with AVD in the upfront treatment of HIV-cHL. The Phase II portion is actively accruing in both the United States and France as part of an AIDS Malignancy Consortium (AMC)/Lymphoma Study Association (LYSA) collaboration. Methods: The Phase I was a 3+3 dose de-escalation design evaluating 3 dose levels of BV (1.2 mg/kg, 0.9 mg/kg, and 0.6 mg/kg) every 2 weeks combined with standard, fixed doses of doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 (AVD) in a 28 day cycle. Eligibility: HIV+ pts diagnosed with untreated cHL stage II-IV with CD4 counts ≥50 cells/mm3 were required to take cART regimens for at least 1 week before treatment. Ritonavir, zidovidine, and cobisistat were excluded. Baseline, cycle 2, and post treatment PET/CT scans were required. Dose limiting toxicities (DLTs) were defined during cycle 1. Results: Sixpts (5 men and 1 woman) were treated in the phase I portion from 3/2013-5/2015. Staging: II (n=1), III (n=1) IV (n=4). Pathology: mixed cellularity (n=2), nodular sclerosis (n=3), and lymphocyte depleted/mixed cellularity (n=1) HIV-cHL. The median CD4 T cell count at lymphoma diagnosis was 499 cells/mm3 (range 86-784) and the median viral load was 44 copies/ml (range 20-77). No cycle 1 DLTs were identified in the first 6 eligible patients and only 3 grade 3 adverse events in later cycles were noted, pneumonia, n=1, and neuropathy n=2, and neutropenia, n=1. In 2 pts, toxicity required delays in therapy of over 3 weeks (after c5d1 and after c6d1) resulting in subject removal from further protocol therapy. One pt had a decrease in the diffusion lung capacity for carbon monoxide (DLCO) to 65% after cycle 2, and BV was withheld while AVD continued as per protocol. Two pts were later deemed ineligible, and excluded from any analysis, due to the concomitant use of ritonavir-based cART at enrollment. Both developed febrile neutropenia and one developed a grade 3 pancreatitis during cycle 1, emphasizing the importance of not treating patients with BV + AVD with concurrent CYP3A4 inhibitors. Five of the 6 pts achieved cycle 2 PET/CT negativity as defined by a Deauville score 1-3. The PET/CT positive patient ultimately had a negative post-therapy scan. The 5 pts who completed therapy achieved CR post-therapy, and one patient has yet to complete treatment. Phase II is enrolling at BV 1.2 mg/kg in combination with AVD. Conclusions: AVD-BV in stage II-IV HIV-cHL was well-tolerated therapy as no DLT were identified. Five of the 6 patients achieved a negative C2 PET/CT and 5/5 of the patients who completed therapy thus far achieved a CR. The recommended Phase II dose is 1.2 mg/kg +AVD every other week. The phase II portion (51 subjects) is actively accruing in both the USA and France, in an AMC/LYSA collaboration, clinicaltrials.gov NCT01771107. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Stroger Hospital of Cook County (CCH) and the Ruth M. Rothstein CORE Center (CC) are the largest health providers for HIV+ patients (pts) in Chicago and among the largest in the United States. Together, CCH and CC treat over 5,500 HIV+ individuals per year and 60 newly diagnosed HIV-associated cancers yearly. In addition, CCH is the largest safety net hospital in Illinois; in the calendar year 2010, it had over 32,000 outpatient hematology/oncology clinic visits. The County Hospital AIDS malignancy project (CHAMP) is a prospective database of all HIV-associated hematological malignancies from 1995 to present. Here we analyzed the demographic, histological, germinal center status, outcome data, and HIV characteristics of pts with AIDS-related diffuse large B-cell lymphoma (AR-DLBCL). As a control, we compared these data to DLBCL pts not infected with HIV, intra-institutionally instead of national historical controls to better understand the AR-DLBCL population of the inner-city, a mostly minority, and one of the largest growing HIV populations. Methods: We screened the CCH cancer registry from 2001 to 2014, and 240 non-HIV pts were identified to have DLBCL. We searched the CHAMP database for cases of DLBCL from the same period. From 196 lymphomas, 51 were identified. Only pts who had a confirmed pathology report as DLBCL were included in this study. We subsequently identified the HIV characteristics, overall survival (OS), and patient demographics for all pts. In addition to OS data in both cohorts, we compared outcomes based on chemotherapy, stage, germinal center (defined by the HANS algorithm), and IPI status. Statistics: Non-parametric Fisher's exact test was used to examine the difference in proportion of pts in both the HIV and non-HIV arm. Survival data were analyzed using Kaplan-Meier analysis and Cox Proportional Hazards model. Results: The M:F ratio was 7.5:1 in AR-DLBCL and 1.9:1 in the non-HIV cohort (P

Description: Introduction: In the pre-highly active anti-retroviral therapy (HAART) era, ITP was a relatively common hematologic abnormality, which was seen in as many as 30% of patients infected with HIV. With the advent of HAART, the incidence of HIV-associated ITP has been reduced substantially, with some epidemiological studies showing contemporary rates as low as 1 to 3% (Vannappagari, Platelets 2011). In cases where HAART does not lead to adequate improvement in platelet counts, next lines of therapy have traditionally consisted of corticosteroids, including dexamethasone and prednisone, intravenous immunoglobulin (IVIG), anti-Rho(D) immune globulin, rituximab and, in the current era, more sparingly, splenectomy. When platelet counts remain persistently 200 cells/ µL, viral loads 〈 40 copies/mL, and platelet counts ≤20 x 109/L before starting TRA therapy. Results: Each patient responded to TRA use with a mean pre-treatment platelet count of 15 x 109/L, and this increased to a mean of 110 x 109/L 6 weeks following treatment initiation. 2 of the patients have maintained a sustained response with adequate platelet counts 3 years after discontinuing TRA therapy. 1 patient succumbed to a myocardial infarction while on eltrombopag and 1 patient, while on romiplostim, expired from complications of a presumed pulmonary embolus after undergoing lumbar spine surgery. Abstract 5014. Table: Characteristics of HIV-related ITP patients given TRA Case Nadir CD4+ count (cells/µL) /HIV viral load (copies/mL) HAART Regimen CD4+ count (cells/µL) /HIV viral load (copies/mL) at time of use of TPA Platelet count pre-TRA treatment Lines of ITP treatment before TRA TRA (dose where response was observed and sustained) 6 month f/u platelet count Sustained Response after stopping TRA (duration) Case 1 261/ 5,000 Atripla® 340 /

Description: Introduction: Stroger Hospital (CCH) and the Ruth M. Rothstein CORE Center (CC) are the largest health providers for HIV+ patients (pts) in Chicago and one of the largest HIV clinics in the United States. CCH/CC treat approximately 5,000 HIV+ individuals per year and 40 newly diagnosed HIV-associated cancers annually. The CHAMP Study was originally a retrospective database from 1990 to 2010 of all clinical, demographic, cancer characteristics of pts diagnosed with HIV/AIDS. Since then, the study has compiled data prospectively on all pts with hematological malignancies. In this study, we analyzed various characteristics of pts with HIV/AIDS diagnosed with lymphoma as well as changes seen over time including therapy response since the implementation of combined anti-retroviral therapy (cART). In addition, we assessed variables including drug use, psychiatric history (hx) and time of HIV diagnosis (dx) with respect to cancer presentation. While large population studies of HIV and cancer exist, few studies specifically examine the largest growing HIV demographic, the inner-city HIV population. Methods: Patient's HIV and cancer clinical, laboratory, and survival data were compiled from the CHAMP database. Psychiatric hx and social factors including drug use and time of HIV dx were also analyzed by retrospective chart review and compared between racial and gender groups as well as differences and overall survival (OS). Survival data was examined using Kaplan-Meier analysis and Cox Proportional Hazards model. Statistical comparisons between different groups were performed via the Fisher's exact test. Results: Between 1995-2018, 226 lymphoma pts were identified spanning 26 diagnoses. Fifty-nine percent, 28%, and 11% were African American (AA), Hispanic, and Caucasian, respectively. The cohort was 87% male. The median age by disease ranged from 35-45. Categorized by cancer type; 32% were diffuse large B-cell lymphoma (DLBCL; n=72), 22.5% classic Hodgkin lymphoma (cHL; n=32), 13% Burkitt lymphoma (BL; n=29), 6.7% primary CNS lymphoma (PCNSL; n=15), and 5% plasmablastic lymphoma (PBL; n=11). Seventy-eight percent of pts presented with stage III/IV disease. CD4+ T cell count (CD4) at dx varied by disease, with the median CD4 count ranging from 19 for PCNSL to 260 cells/µL in cHL. DLBCL pts treated with DAEPOCHR (n=23) had a 5-year OS of 80% vs. 68% treated with CHOPR (n=35; p=0.4). cHL had a 5-year OS of 76%. PBL and BL had a 10-year OS of 62% and 58%, respectively. Cases of cHL decreased from 48% of all lymphomas in 2012 (n=8) to 9% in 2017 (p

Description: Abstract 2807 Background: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) are the most common non-HIV-defining and HIV-defining malignancies, respectively1. Patients (pts) treated for lymphoma concomitantly with highly active retroviral therapy (HAART) have much better response rates and overall survival2. However, few studies have assessed the impact of HAART on the adverse events of chemotherapy. The Stanford V regimen for HL has a 48 % increase in neurotoxicity and neutropenia when taken concomitantly with HAART compared to non-HIV patients3. Case reports exist associating gastrointestinal and neurotoxicity with vinblastine (less so vincristine) and ritonavir-based HIV therapy. Unfortunately, the frequency of this association has yet to be shown. We retrospectively analyzed pts at our institution with lymphomas and HIV and the relationship between HAART and chemotherapy adverse events (AE) in an attempt to minimize future chemotherapy-related complications. Methods: We retrospectively identified HIV infected patients treated for lymphoma (2002-2008) at Stroger Hospital of Cook County by computer database search using ICD9 and pharmacy codes and then confirmed by medical record review. The adverse events during chemotherapy were assessed by chart review and graded per the NCI Common Terminology Criteria for Adverse Events. Those pts where HAART or chemotherapy regimen could not be confirmed were excluded from the study. Patient, disease, and the HIV characteristics were assessed. Statistics: A non-parametric Fisher's exact test was used to examine the difference in proportion of patients that developed an adverse event in the pts with a particular HAART medication and the ones without. Results: Twenty-five HIV infected pts with HL and 46 pts with NHL were identified. Identification of HAART administered during chemotherapy was found in 23/25 (92%) pts with HL and 22/46 (48%) pts with NHL. Patients diagnosed with HL were 87% male with a median age of 43. Mixed cellularity (26%) and nodular sclerosis (26%) pathologies were the most common with 60% (14/23 pts) presenting as stage III/IV disease. The median CD4 count at diagnosis was 174 cell/ml with a range of 26–341. The most common HAART regimen was efavirenz/emtricitabine/tenofovir (17%), though ritonavir-based regimens accounted for 48% of all HIV treatments. Twenty-six percent (6/23 pts) had neurotoxicity (13% G3, 4% G2, 8% G1) and among those with any neurotoxicity,100% were taking ritonavir. Each of the 3 pts with G3 neurotoxicity, and the patient with G3 constipation experienced their AE after just 1 to 2 doses of vinblastine (before cycle #2). Each pt with G3 neurotoxicity, vinblastine was held with only slight improvement in symptoms. A statistically significant difference in the proportion of patients that developed neurotoxic effects after initiation of vinblastine was observed in the ritonavir vs. non-ritonavir based HAART therapy groups (55% vs. 0%, p

Description: Introduction Stroger Hospital of Cook County (CCH) and Ruth M. Rothstein CORE Center (CC) are the largest health providers for HIV + patients in Chicago and among the largest in the United States. Together, CCH and CC treat over 5500 HIV + individuals per year and 60 newly diagnosed HIV-associated cancers yearly. In addition CCH is the largest safety net hospital in the Chicago, and in the calendar year 2010 had over 32,000 outpatient hematology/oncology clinic visits. Classical Hodgkin lymphoma (cHL) is the second most common non-AIDS defining cancer at CCH. Recent reports have suggested that the outcomes of HIV (HIV-cHL) vs. non-HIV associated cHL were similar. Many of these studies were multi-institutional, and insights into the inner-city cancer population have yet to be described. In addition, many of these studies compared outcome data to historical controls obtained at different institutions. To gain insights into the racial composition and survival data of patients with cHL, we compared all of disease characteristics and demographic information of HIV-associated and non-HIV cHL at CCH and the CC from the past 15 years. Methods We identified via CCH and CC databases HIV-infected patients with cHL from 1998–2013. We subsequently identified the HIV characteristics, cancer type, overall survival (OS) data, and patient demographics for all patients. Four hundred patients with cHL were screened. Only patients that had complete overall survival and demographic information were included in the study. One hundred seventy-nine non-HIV and 40 HIV-cHL met these criteria. In addition, all patients analyzed were treated with the same treatment regimen, Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD). Statistics Non-parametric Fisher's exact test was used to examine the difference in proportion of patients in both the HIV and non-HIV arm. Survival data were analyzed using Kaplan-Meier analysis and Cox Proportional Hazards model. Results The M:F ratio was 8.5:1 in HIV-cHL and 2.4:1 in the non-HIV cohort (P