Extraoral plasmablastic lymphoma with intravascular component and MYC translocation

Plasmablastic lymphoma (PBL) is an uncommon, clinically aggressive, Epstein-Barr virus–driven B-cell lymphoma that was initially described in tumors of relatively young human immunodeficiency virus–positive men. Subsequent to initial reports, the clinical and pathological spectrum of this disease has been expanded such that, now, PBL is recognized to be a heterogeneous disease entity. Plasmablastic lymphoma has been seen in clinical settings outside those initially reported and has been shown to demonstrate a variety of morphologic patterns. We describe a case of extraoral PBL in an human immunodeficiency virus–infected patient with a computed tomography–identified heterogeneously enhancing mass in the stomach. Histologically, a prominent intravascular component was identified. Fluorescent in situ hybridization analysis for MYC/IGH (immunoglobulin heavy chain) rearrangement t(8;14) identified fusion signals, confirming the presence of MYC rearrangement. The presence of a prominent intravascular in our case is unique. To our knowledge, these findings have not been observed in the previous reports of PBL. The observation of this vascular component supports the heterogeneity of PBL and may be an indicator of tumor aggressiveness. We were able to demonstrate the MYC/IGH rearrangement in our case of PBL. The interplay between Epstein-Barr virus and this MYC rearrangement may be similar to what is observed in Burkitt lymphoma, another clinically aggressive non–Hodgkin lymphoma

Sustained Responses to Thrombopoetin Analogs in HIV Patients with Refractory ITP

Abstract Abstract 1165 Thrombocytopenia(TP) is common in patients with Human Immunodeficiency Virus (HIV) infection, reported in as many as 10–30% of patients and seen more often in IV drug users and advanced HIV infection even in post-HAART era. Both decreased production of platelets and increased destruction have been proposed as mechanisms of thrombocytopenia and at least 2 different clinical scenarios have been described: patients with very advanced AIDS, being thrombocytopenia another manifestation of bone marrow suppression; and patients without significant T-cell depletion in whom thrombocytopenia develops likely as an immune phenomenom, “ITP-like” HIV-related thrombocytopenia (HIV-TP). In HIV-TP, common treatments for classical ITP have been reported including corticosteroids, danazol, splenectomy, Intravenous Gammaglobulin, interferon, Anti-D, dapsone and splenic radiation with varying degrees of success with the highest responses seen with the use of HAART. Romiplostim (RMP) and Eltrombopag (ETP) are thrombopoeitin agonists (TA) approved in 2009 for refractory ITP and recently proposed to be used as first-line agents. No reports of the use of TA in patients with HIV-ITP are available to date. 5 patients with HIV-related ITP were treated with TP in our centers between 2009 to 2011. Mean age was 48 years (25–61), 4 males and 1 female. All of the patients had failed or relapsed after prednisone, 3 of the patients had also failed multiple treatments including splenectomy (1 patient), IVIG, Rho(D) immune globulin, Rituximab, danazole and vincristine. All but 1 of the patients were on HAART by the time of treatment and CD4 counts were <200 cells/μL in 2 patients (10–157 cells/ μL). All 5 patients were treated initially with RMP at the starting dose of 1 mcg/Kg and titrated as per guidelines. One patient requested to be switched to ETP and developed an acute lower extremity DVT and symptomatic PE 1 week after starting the medication. Responses to treatment are shown in graph 1. Mean baseline Platelet count was 27 × 103/μL (13–40 × 103/μL) and it increased to 66 × 103/μL (45–86 × 103/μL) within 1 week and 76 × 103/μL (45–107 × 103/μL) after 1 month of therapy, 2.8 times the baseline (2.1 – 3.4 × baseline value). 4 patients achieved a platelet count ≥50 × 103/μL within 1 month. 4 of the patients had durable responses for ≥ 12 months not requiring dose adjustments or modifications; the other patient had several compliance issues and missed several doses of RMP, his platelet count improved every time the medication was restarted. We present the first report of the successful and sustained use of TA in patient with HIV- ITP. Disclosures: Byrnes: Amgen: Honoraria, Speakers Bureau

Gemcitabine (G) and nab-paclitaxel (nab-P) in patients with refractory advanced pancreatic cancer (PC).

373 Background: There is no standard chemotherapy regimen for PC patients who have progressed on G and fluoropyrimidine-based therapy. Single agent nab-P had limited activity on a second-line phase II trial in PC. Synergistic preclinical studies with G and taxanes have been reported. Nab-P targets stromal cells and leads to improved delivery of chemotherapy to PC cells. The combination of G + nab-P might be an effective approach in pretreated PC. Methods: A retrospective analysis of advanced refractory PC patients treated from Sep 2010 to Aug 2011 with the combination of G + nab-P was performed at the Sylvester Comprehensive Cancer Center. Patients received G 1000mg/m2 and nab-P 100mg/m2 on D1, 8 and 15 of a 28 day cycle. Treatment response was assessed by review of imaging studies using the RECIST criteria, CA19-9 response and symptomatic improvement. The progression-free survival (PFS) and overall survival (OS) were calculated from time of commencement of G + nab-P until documented progression or death respectively. Results: 10 patients were treated with G + nab-P; 60%, 30% and 10% of patients had received 3, 2 and 1 prior chemotherapy regimen. 90% and 80% received prior G or fluoropyrimidine-based regimen respectively. Therapy was discontinued in one patient following only one dose of G + nab-P (Cycle 1, day 1) due to grade 2 thrombocytopenia. The remaining 9 patients received a median of 4 cycles. Two (22.2%) patients had confirmed PR, 3(33.3%) patients had confirmed stable disease while 4 (44.4%) patients progressed on therapy. The median PFS was 13.7 weeks. The median PFS was 20 weeks in patients with PR or SD and 9.9 weeks in patients with PD. Recurrent malignant ascitis resolved in a patient with peritoneal carcinomatosis. Treatment was well tolerated; grade 3-4 hematologic toxicity included anemia, thrombocytopenia and neutropenia in 2, 1 and 2 patients respectively. 70% of patients required G-CSF support. Non hematologic Grade 3-4 toxicities included fatigue, peripheral neuropathy; nausea and vomiting in 3, 2 and 1 patient respectively. Conclusions: G + nab-P resulted in clinical benefit in half of this group of advanced PC patients who had previously progressed on G and fluoropyrimidine-based regimens

Oral and Extraoral Plasmablastic Lymphoma: Similarities and Differences in Clinicopathologic Characteristics

Abstract Plasmablastic lymphoma (PBL), initially characterized as an aggressive lymphoma arising in the jaw and oral mucosa in HIV-infected patients, was recently reported to occur with extraoral manifestations, heterogeneous histologic findings, and variable association with immunodeficiency states. We reviewed clinical, morphologic, and immunophenotypic features of 13 cases of PBL to determine whether these different subtypes represent distinct morphologic and clinical entities. Two distinct subtypes of PBL were identified and classified as oral and extraoral PBL. The oral PBLs were strongly associated with HIV infection and commonly demonstrated plasmablastic morphologic features without plasmacytic differentiation. Extraoral PBLs tended to occur in patients with underlying non–HIV-related immunosuppression and universally demonstrated plasmacytic differentiation. The patients with oral PBL demonstrated better overall survival compared with patients with extraoral PBL (P = .02). Our findings suggest that PBL with oral and extraoral manifestation represent 2 distinct clinicopathologic entities.</jats:p

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma

The phase III MPACT trial for metastatic pancreatic cancer (PC) showed improved overall survival (OS), progression free survival (PFS) and response rates (RRs) for first-line nab -paclitaxel (Abraxane) and gemcitabine (the AG combination) compared to gemcitabine monotherapy. The safety and efficacy of the AG combination has not been systematically studied as second-line therapy or beyond for metastatic PC. We conducted an IRB-approved retrospective analysis of all patients diagnosed between September 2010 and August 2014 with advanced refractory PC that received combination treatment with AG at our institution. Demographic and survival data were extracted from the registry. Patients received nab -paclitaxel 125 mg/m 2 and gemcitabine 1,000 mg/m 2 and on days 1, 8 and 15 of a 28-day cycle with subsequent dose modifications based on tolerance. Data on 59 patients was available; the median age was 61; 55% were male; 56% received AG as second line therapy and 44% received it as third-line or beyond. Five (10%) patients had a confirmed partial response (PR), 23 (47%) had stable disease (SD) and 21 (43%) had disease progression as their best response. Among the 31 (52%) patients who received prior gemcitabine, 18 (58%) had clinical benefit; 3 had a PR and 15 had SD. The median OS was 3.9 months and the median progression-free survival was 3 months. Toxicity was similar to what was reported in the MPACT trial. This retrospective analysis suggests that AG is active in PC patients previously treated with either fluoropyrimidine-based therapy or gemcitabine-based therapy with manageable toxicities

Gemcitabine (Gem) and nab-paclitaxel (nab-P) in patients (pts) with refractory advanced pancreatic cancer

413 Background: The combination of nab-P and Gem improves survival compared to Gem alone in first-line therapy of metastatic pancreatic cancer. Efficacy data with this doublet in previously treated pts are scant. Our group presented preliminary results on 10 pts treated with this two-drug combination in the second and third line setting and herein present updated data on 59 pts. Methods: This IRB approved analysis identified all pts diagnosed with advanced refractory pancreatic cancer, treated with second-line Gem and nab-P at University of Miami and Sylvester Comprehensive Cancer Center between September 2010 and June 2014. Response by RECIST, CA19-9, and symptomatic improvement were assessed. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of Gem + nab-P and were analyzed using the Kaplan-Meier method. Clinical benefit was defined as the percentage of patients with a partial response (PR) or stable disease (SD). Results: Data from59 pts were analyzed. The median age was 60; 55% were male; 54% received Gem + nab-P as second line therapy and 46% received it as third-line or beyond. Five (10%) pts had confirmed PR, 23 (47%) SD and 21 (43%) progressed. Among the 31 (52%) pts who received prior Gem, 18 (58%) had clinical benefit, 3 PR and 15 SD. The median OS was 3.9 months. The median PFS was 3 months. Toxicity appears similar to what has been reported on the MPACT trial with the combination. Conclusions: The clinical benefit seen withGem and nab-P in this group of pretreated pancreatic cancer pts suggests that it can be considered as an option. Additionally, prior Gem treatment appears not to decrease Gem and nab-P benefit in this population. Since nab-P monotherapy has modest activity in pre-treated pancreatic cancer pts, our data suggests a positive interaction between Gem and nab-P that may overcome resistance to Gem. [Table: see text

The value of tissue protein expression as a predictor of efficacy for first- or second-line therapy (tx) in metastatic ductal pancreas cancer (PDAC) in patients (pts) receiving either gemcitabine (G)-based tx or 5FU (F)-based tx

460 Background: No validated biomarkers exist to direct treatment decisions in PDAC. Decisions regarding tx choices are based on age, organ function, and performance status. Defining predictors of efficacy to F (alone or in combination) or G (alone or in combination) in PDAC are urgently needed. Histologic subtype by immunohistochemistry (IHC); pancreatobiliary type (PB), intestinal type (I), gastric type (Ga) and intestinal/gastric type (I/G); may predict benefit to G or F. Methods: Charts of PDAC pts from 2 institutions from 2007 to 2013 having both pathology specimen and a qualifying tx (FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine or G or G and nab-paclitaxel) were reviewed. IHC phenotypes were defined by staining >25% CDX2 = I, >25% MUC5 = Ga, >25% CDX2 and MUC5 = I/G, >25% MUC1 = PB. Results: 51 pts were identified. 4 cases had Stage II disease without recurrence after adjuvant tx and were excluded. 5 tumors were PB, 1 I, 3 I/G, 38 Ga. 41 (87%) had Ga or I/G type. Due to lack of statistical power for the other histologic subtypes, response to F or G was only analyzed in the 35 metastatic pts with the Ga subtype. 14 were metastatic at diagnosis. 24 males. Median age 57. 21 Hispanic, 14 Non-Hisp. The PFS for Ga treated with F based tx (>12 m) versus G (~9 m) based tx in the 1st line approached statistical significance (p=0.050). In multivariable analysis with adjustments for clinical stage, ECOG, age at dx, there was a significant lower risk of progression in pts treated with F based tx versus G based tx (HR=0.278, p=0.0315). Conclusions: There was near statistical significance favoring F based tx over G based tx in PDAC Ga subtype (p=0.05). Historically, G has proven superior to F as a single agent but our findings suggest F in combination may be superior to G in combination, at least for the treatment of Ga subtype