Recurrent non-Hodgkin Lymphoma Research Articles

NON-HODGKIN FOLLICULAR LYMPHOMA COMPLICATED BY HISTOPLASMOSIS-INDUCED CHYLOTHORAX AND PNEUMOHYDROPERICARDITIS SECONDARY TO AN ESOPHAGOPERICARDIAL FISTULA

NON-HODGKIN FOLLICULAR LYMPHOMA COMPLICATED BY HISTOPLASMOSIS-INDUCED CHYLOTHORAX AND PNEUMOHYDROPERICARDITIS SECONDARY TO AN ESOPHAGOPERICARDIAL FISTULA

MULTIPLE CHEST CT FINDINGS IN A POST-TRANSPLANT PATIENT

SESSION TITLE: Fellows Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary complications are common in hematopoietic stem cell transplantation recipients. Late complications occur more than 100 days after HSCT. During this time frame noninfectious causes are more common than infectious complications. CASE PRESENTATION: 57 y/o Panamanian female never-smoker with history of Common Variable Immune Deficiency, and recurrent non-Hodgkin lymphoma status post-chemotherapy and autologous stem cell transplant 2015 followed by allogeneic bone marrow transplant in 2017 presented with dyspnea and non-productive cough. She had presumed pneumonia two months prior but denied infectious or constitutional symptoms. Initial CT chest demonstrated diffuse bilateral GGOs and PFTs had a restrictive pattern with decreased DLCO. PET CT lacked findings suggesting recurrent lymphoma and connective tissue disease. Initial differential diagnosis included infection, organizing pneumonia, and eosinophilic lung disease. The patient underwent bronchoscopy with bronchoalveolar lavage (negative cultures and cytology). Prednisone therapy for presumed cryptogenic organizing pneumonia was initiated. Shortly after she developed worsening dyspnea, tachycardia and new exertional hypoxia and was found to have pneumomediastinum. Bronchoscopy was repeated and again cultures and cytology negative and TTE demonstrated only mild diastolic dysfunction. Without an alternative diagnosis treatment for PCP was provided for 21 days and 50 mg prednisone continued. At completion of treatment there was no improvement on her CT. A surgical lung biopsy was performed, and multidisciplinary radiologic-pathologic diagnosis of pleuroparenchymal fibroelastosis (PPFE) was rendered. DISCUSSION: Predominant findings such as the GGO and pneumomediastinum, can overshadow less conspicuous features such as PPFE which can be confounding. PPFE is a rare disorder usually occurring between age 40 to 70. Numerous potential risk factors for the development of PPFE have been described most common of which are bone marrow, hematopoietic stem cell and lung transplant along with CTD, familial, post infectious, and idiopathic. Clinical features include exertional dyspnea, insidious dry cough, and weight loss. Typically a restrictive ventilatory defect and reduced DLCO are noted. In 2012 Reddy and colleagues proposed diagnostic criteria integrating histopathologic and radiographic features included bilateral upper zone pleural thickening with associated subpleural fibrosis on CT and intraalveolar fibrosis and elastosis on histopathological exam. Pneumothorax and pneumomediastinum are frequent complications of PPFE. CONCLUSIONS: PPFE is a rare condition but should be considered in patients a history of transplant. Treatment remains a clinical challenge and lung transplant is an option. In our patient, possible contributing factors for the development of PPFE were recurrent pulmonary infection and late-onset complication following HSCT. Reference #1: Pena E, Souza CA, Escuissato DL, et al. Noninfectious pulmonary complications after hematopoietic stem cell transplantation: practical approach to imaging diagnosis. Radiographics 2014; 34: 663–683 Reference #2: Chua, F, Desai, SR, Nicholson, AG, et al. Pleuroparenchymal fibroelastosis: a review of clinical, radiological and pathological characteristics. Ann Am Thorac Soc 2019; 16: 1351–1359 Reference #3: Reddy TL, Tominaga M, Hansell DM, von der Thusen J Jr, Rassl D, Parfrey H, Guy S, Twentyman O, Rice A, Maher TM, et al. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J 2012;40:377–385 DISCLOSURES: No relevant relationships by Sally Delvecchio, source=Web Response No relevant relationships by Teri Franks, source=Web Response No relevant relationships by Jeffrey Galvin, source=Web Response No relevant relationships by Michael Luca, source=Web Response

Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas

Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas

CD19-CAR Therapy Using Naive/Memory or Central Memory T Cells Integrated into the Autologous Stem Cell Transplant Regimen for Patients with B-NHL

Autologous stem cell transplantation (ASCT) remains an important consolidative therapy for patients with recurrent non-Hodgkin lymphoma (NHL), but is limited by the high incidence of NHL relapse. We report a Phase I clinical trial of ASCT followed by CD19-specific CD28-costimulatory chimeric antigen receptor (CD19:28z-CAR) T cells, with the goal of reducing NHL relapse rates. Safety and feasibility were the primary objectives, with CAR T cell persistence and expansion in the myeloablative ASCT setting as secondary objectives.This study examines safety and feasibility for two manufacturing platforms that differed in the T cell subset composition used for CAR engineering. Initially, the T cell population for CAR transduction was central memory (Tcm)-enriched: participants' peripheral blood mononuclear cells (PBMC) were depleted for CD14+ monocytes, CD25+ Tregs, and CD45RA+ naïve and stem-memory T cells, after which they were selected for CD62L+ Tcm (Wang et al. Blood;127:2980). Based on comparative preclinical data, a second arm was added to the trial to evaluate a Tn/mem-derived manufacturing platform that enriched central memory, naïve, and stem memory T cells (no CD45RA+ depletion). Either Tcm- or Tn/mem-enriched T cells were activated with CD3/CD28 beads, transduced with lentiviral vector encoding the CD19:28z-CAR, and expanded ex vivo.This phase I trial used the toxicity equivalence range design (Blanchard and Longmate. Contemp Clin Trials; 32;114) with an equivalence range for DLTs of 0.20-0.35 and a target toxicity rate of 0.25. The first 3 participants on each arm were followed one at a time, with later accrual in cohorts of 3. Twenty-three participants underwent ASCT and received CD19:28z-CAR T cells 2 days post stem cell infusion at the assigned dose level (DL): 17 on the Tcm arm (DL 50 million [M] CAR+ T cells [n=3], 200 M [n=5], 600 M [n=9]); 6 on the Tn/mem arm (DL 200 M). Participants were followed for dose limiting toxicity (DLT) for 28 days. Table 1 shows results by arm and DL. Both arms demonstrated safety and feasibility. There was no delayed hematopoietic reconstitution on either arm. On the Tcm arm, the only DLT was at DL 600 M (1 of 9 at 600 M). The Tn/mem arm was opened at 200 M and 6 participants were treated with no DLTs. The dose was not escalated as the protocol management team had seen activity at the 200M level in 2 other trials using the Tn/mem product.Tcm Arm: Fourteen of 17 participants (82%) had a diagnosis of diffuse large B-cell lymphoma (DLBCL) and 3 had mantle cell lymphoma. The mean age of the participants on the Tcm arm was 57 (35-75). The median number of prior chemotherapy regimens was 2 (1-5). The median progression-free survival (PFS) was 34.6 months 95% CI [21.8, undefined]. Seven of 17 participants (41%) have progressed, 1 died in remission of unrelated intracranial hemorrhage (6%), 7 (41%) remain in CR and are still in follow-up, and 2 are lost to follow-up (12%). All 17 participants achieved a CR or a continuing CR after ASCT and T cells.Tn/mem arm: Five of 6 participants (83%) had a DLBCL diagnosis, and 1 was NHL not otherwise specified. The mean age of the participants was 50 (40-72). The median number of prior chemotherapy regimens was 2.5 (1-3). The median follow-up time for the Tn/mem arm was 12 months, with median PFS not yet reached. One of 6 (17%) has progressed, 4 (66%) remain in CR and are still in follow-up, and 1 is lost to follow-up (17%). Five of 6 (83%) participants achieved a best response of CR or continuing CR after therapy.Several differences were observed between the manufacturing platforms. Since the Tn/mem production platform has fewer depletion steps, it resulted in a higher product yield, which shortened the ex vivo expansion period by 4.1 days (95% CI [1.5%, 6.6%]) from 18.9 days (15-24) for Tcm to 14.8 days (12-18) for Tn/mem (P<0.005). Notably in the ASCT minimal disease burden setting, the Tn/mem-derived CD19:28z-CAR T cell products exhibited significantly higher in vivo CAR T cell expansion compared to Tcm products at the 200M DL (Figure 1). We conclude that although both Tcm- and Tn/mem-enriched CD19CAR T cell therapies are safe, the Tn/mem product is more promising due to its 1) shorter production time, 2) higher cell yield, and 3) better in vivo expansion, despite the low antigen drive in these patients post-salvage and ASCT therapy. Longer follow-up for the 2-year PFS secondary objective will indicate if improved Tn/mem expansion impacts tumor control. DisclosuresWang:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Budde:Mustang Therapeutics: Consultancy, Other: Licensing Agreement, Patents & Royalties, Research Funding. Brown:Mustang Therapeutics: Consultancy, Other: Licensing Agreement, Patents & Royalties, Research Funding. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Outcomes of Patients with Recurrent and Refractory Lymphoma Undergoing Allogeneic Hematopoietic Cell Transplantation with BEAM Conditioning and Sirolimus- and Tacrolimus-Based GVHD Prophylaxis

The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited. In this retrospective study, we reviewed outcomes of 22 patients with recurrent and refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range, 1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95% CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n = 12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had undergone previous alloHCT. Both patients with previous ASCT developed severe regimen-related toxicity. Patients who underwent alloHCT with chemorefractory disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%, respectively. In conclusion, alloHCT with a BEAM preparative regimen and tacrolimus/sirolimus-based GVHD should be considered as an alternative option for patients with highest-risk lymphoma whose outcomes are expectedly poor after ASCT.

FIRST CLINICAL RESULTS OF ADCT‐402, A NOVEL PYRROLOBENZODIAZEPINE‐BASED ANTIBODY DRUG CONJUGATE (ADC), IN RELAPSED/REFRACTORY B‐CELL LINEAGE NHL

Introduction: CD19 expression has been demonstrated in many types of NHL, including FL and DLBCL. Pyrrolobenzodiazepine (PBD) is a DNA cross-linking agent. ADCT-402, a humanized antibody directed against human CD19 conjugated to a PBD dimer toxin, has demonstrated potent pre-clinical anti-tumor activity against CD19-expressing B-cell malignancies. Interim results of the first in-human clinical study of ADCT-402 in the difficult-to-treat relapsed/refractory NHL setting are reported here. Methods: Patients (pts) with recurrent B-cell NHL who had failed or were intolerant to established therapies, or had no other treatment options available, were assigned IV infusions of ADCT-402 every 3 weeks (1 cycle) according to a 3 + 3 dose-escalation study design. No intra-patient dose escalation was allowed. Safety, tolerability, and efficacy were assessed. Results: As of 3 Feb 2017, 37 pts (23 male, 14 female; median age: 69 years [range 24–85]; median number of previous therapies: 3 [range 1–10]) have been recruited. Diagnoses included DLBCL (n = 22), MCL (n = 7), FL (n = 6) and other B-cell NHL (n = 2). Pts received ADCT-402 doses ranging from 15 to 200 μg/kg (median cycles: 3 [range 1–11]). Treatment-emergent adverse events (TEAEs) included fatigue (21 [56.8%] pts), peripheral edema (10 [27.0%] pts), and nausea (9 [24.3%] pts). Grade ≥ 3 TEAEs included decreased neutrophil count (4 [10.8%] pts), increased γ-glutamyltransferase (3 [8.1%] pts), neutropenia (3 [8.1%] pts), and thrombocytopenia (2 [5.4%] pts). TEAEs in 4 (10.8%) pts led to ADCT-402 withdrawal (increased γ-glutamyltransferase; increased blood alkaline phosphatase and γ-glutamyltransferase; fatigue and edema; abdominal pain and myalgia). No DLTs were reported and the MTD was not reached. 15/34 (44.1%) evaluable pts achieved a CR or PR (overall response [OR]), including 9/22 (40.9%) pts with DLBCL. 2/15 pts progressed by data cut-off. One 30 μg/kg pt continues in CR for >24wks. Table 1 shows the best OR by dose. 10/17 (58.8%) pts in the ≥120 μg/kg cohort achieved OR, including 7/12 (58.3%) with DLBCL. Figure 1 shows nodal regression. Preliminary PK and anti-drug antibody data will be reported at the meeting. Conclusions: ADCT-402 demonstrates encouraging single-agent anti-tumor activity and manageable toxicity in recurrent B-cell lineage NHL. At doses >120 μg/kg, the OR in DLBCL is 58%. Further evaluation in specific NHL subtypes is warranted. A dose expansion in DLBCL is planned. http://clinicaltrials.gov/show/NCT02669017 * Best visit response based on the 2014 Lugano Classification Criteria Key: CR, complete response; OR, overall response (CR+PR); PD, progressive disease; PR, partial response; SD, stable disease Keywords: CD19; diffuse large B-cell lymphoma (DLBCL); non-Hodgkin lymphoma (NHL).

Acute hepatitis B virus infection with delayed appearance of hepatitis B core antibody in an immunocompromised patient: a case report

BackgroundDespite the introduction of universal hepatitis B immunization programs worldwide, outbreaks of acute infection still occur in unimmunized individuals. A timely diagnosis of hepatitis B is necessary to ensure adequate clinical care and public health interventions that will reduce transmission. Yet, interpretation of hepatitis B serological markers can be complex. We present a case of hepatitis B with atypical markers, including delayed appearance of hepatitis B core antibody. Case presentationA 62-year-old white woman was identified as a sexual contact of a male individual with acute hepatitis B virus infection. She had a history of recurrent low-grade non-Hodgkin lymphoma and had recently received immunosuppressive therapy. At baseline she had a negative serology and received three double doses (40 μg) of Engerix-B vaccine (hepatitis B vaccine) with a 0-month, 1-month, and 6-month schedule. One month following the last dose, hepatitis B surface antigen was positive in the absence of hepatitis B core antibody. The only sign of infection was a slight elevation of alanine aminotransferase enzymes a few months after first sexual contacts with the male individual. Hepatitis B virus infection was later confirmed despite the absence of hepatitis B core antibody. The development of hepatitis B core antibody was finally noted more than 6 months after the first positive hepatitis B surface antigen and more than 12 months after elevation of alanine aminotransferase enzymes. Immunosuppression including rituximab treatment was the most likely explanation for this serological profile. On her last medical assessment, she had not developed HBeAg seroconversion despite lower hepatitis B virus deoxyribonucleic acid levels with tenofovir treatment.ConclusionsWhen confronted with positive hepatitis B surface antigen in the absence of hepatitis B core antibody, consideration should be given to the possibility of both acute and persistent infection particularly in the setting of immunosuppression so that appropriate clinical management and public health interventions can take place. Given the increasing use of biologicals such as anti-tumor necrosis factor therapies either alone or with other immunosuppressive agents, this phenomenon may be encountered more frequently.

Beac and BEAM High-Dose Chemotherapy in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation Are Efficacious, with Comparable Toxicity

Introduction: Autologous stem cell transplantation (ASCT) is currently considered the standard first-line consolidation therapy for younger patients with mantle cell lymphoma (MCL). In general, there are limited data regarding a preferred high-dose therapy (HDT) regimen preceding ASCT to be used in patients with non-Hodgkin lymphoma (NHL). Although BEAM and BEAC regimens (including BCNU, etoposide, cytosar in both regimens and melphalan or cytoxan, respectively) have been commonly employed as conditioning HDT in patients with aggressive or recurrent NHL, there have been few reports comparing these two regimens. A retrospective analysis found the superiority of BEAM over BEAC in terms of overall survival (OS) and event-free survival (EFS). Regimen-related toxicities were similar, except that BEAM was associated with more frequent lower gastrointestinal mucositis. Other studies reported that these two regimens had equivalent efficacy and outcome, as measured by EFS and OS. Further studies are required to define the optimal regimen for each specific NHL subtype. The current study aimed to compare the efficacy and toxicity of BEAC versus BEAM as a consolidation HDT in young patients with MCL undergoing ASCT.Methods: This is a retrospective analysis of outcomes in patients with MCL who received high-dose chemotherapy with BEAM or BEAC regimen followed by ASCT in two bone marrow transplant centers in Israel. OS, progression-free-survival (PFS) and regimen toxicity were compared. Results: Fifty five patients with MCL who were diagnosed between 1995-1/2016 and received consolidation with BEAC or BEAM HDT regimen were included in the analysis. Twenty seven patients were treated with BEAM and 28 patients - with BEAC. No significant differences between the two groups were revealed in terms of age, sex, the Mantle Cell Lymphoma International Prognostic Index (MIPI), induction treatment protocol and percentage of patients who were transplanted at first complete response (CR1) (Table 1). The amount of infused CD34 cells was significantly higher in the BEAM group, and the number of days until platelet engraftment was significantly greater in the BEAC group. There were no differences in the number of blood transfusions or hospitalization days between the groups (Table 2). In terms of HDT toxicity, there was a trend to a higher rate of grade 3-4 upper mucositis with BEAM protocol; no other differences in toxicity between the regimens were observed (Table 3). Non-relapse mortality at day 30 post-transplant was 0% in both groups. A median follow-up of surviving patients was 31 (range 1-119) months. PFS at 3 years in patients receiving BEAM and BEAC was 65% and 78%, respectively (p=.75). In univariate analysis, age less than 60 years, low-to-intermediate MIPI and transplant at CR1 were found to significantly improve PFS, while no difference in PFS was found between the two treatment regimens. In multivariate analysis, low-to-intermediate MIPI and transplant at CR1 appeared to significantly increase PFS (P = 0.02 and 0.03, respectively). There was no difference in the 3-year OS between the two HDT regimens (58% in the BEAM group and 81% in the BEAC groups; p=.31). Conclusion: BEAC and BEAM high dose chemotherapy regimens followed by autologous stem cell transplantation have similar efficacy and toxicity in patients with MCL. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Case Series of Non-Hodgkin's Lymphoma Recurrence in Lower Extremities Mimicking Deep Vein Thrombosis

Background: While uncommon, non-Hodgkin's Lymphoma (NHL) can relapse in extranodal sites in the lower extremities. It is well established that venous thomboembolism occurs in higher incidence in patients with underlying malignancy. We describe 3 cases of NHL in which relapsed disease was discovered after lower extremity swelling prompted evaluation for deep vein thrombosis (DVT), and revealed recurrent NHL. CASE 1: A 61 YO F with history of Stage IEA Marginal Zone Lymphoma (MZL) of the dura diagnosed in 2012 received treatment with whole-brain and local brain radiation. In 2016 she developed recurrence in cervical lymph nodes. Six months after receiving 4 cycles of bendamustine and rituximab she developed left leg pain and calf swelling. PET/CT showed a hypermetabolic lesion in left tibia. MRI confirmed large lesion in mid-shaft of tibia extending down the length of the bone. CT-guided bone biopsy confirmed MZL. CASE 2: A 67 YO F with history of triple-negative inflammatory breast cancer treated in 2000 with neoadjuvant chemotherapy and mastectomy. PET/CT in 2008 showed 2 left femoral lesions. She underwent CT-guided bone biopsy of femoral lesion which confirmed follicular lymphoma (FL). Interim PET/CT in 2010 showed decreased FDG uptake in left femur. She was followed with watchful waiting. Then in 2014 patient developed leg swelling and pain, thought to be a DVT. Duplex ultrasound of the lower extremity was negative. PET/CT showed a left inguinal mass and left calf mass. MRI confirmed large mass within the left lower leg centered on the left fibular diaphysis with a very large associated soft tissue component with extensive muscular and neurovascular involvement. Biopsy of left inguinal lymph node confirmed diffuse large B-Cell lymphoma (DLBCL). CASE 3: A 61 YO M with history Stage IV FL in 1988 and initially treated with 4 cycles of PROMACE-CytaBOM. He relapsed nodally in 1995 and was treated on the IDEC investigational protocol with rituximab which led to a complete remission. In 2001 he developed a subcutaneous nodule on his back, biopsy showed FL, grade 1. A staging CT scan of neck, chest, abdomen, and pelvis was unremarkable, but a PET scan showed left axillary disease. He was re-treated with rituximab and local radiation which led to a complete response. Patient presented in 2008 with right calf swelling. Ultrasound at that time showed no DVT but confirmed swelling and suggested right inguinal adenopathy. PET/CT showed FDG uptake in multiple areas in groin and pelvis plus extensive uptake in thickened calf muscles extending from the right knee to the toe. Biopsy of right inguinal lymph node confirmed FL. Conclusion: Among NHLs, relapse patterns can vary significantly. Timing and frequency of relapse is largely dependent on whether NHL is classified as indolent or aggressive. However, location of relapsed disease in NHL is less well established. NHL relapse can occur in a fashion mimicking DVT with lower extremity swelling. When patients with history of NHL present with lower extremity swelling, relapsed disease should be included in the differential diagnosis. Table Patient characteristics Table. Patient characteristics Disclosures Cohen: Takeda Oncology: Honoraria; Pharmacyclics: Honoraria; Seattle Genetics: Honoraria; Amgen: Honoraria. Broome:True North Therapeutics: Honoraria; Alexion Pharmaceuricals: Honoraria.

Massive Pelvic Lymphadenopathy Due to Recurrent Non-Hodgkin Lymphoma Incidentally Revealed on a 99mTc-MDP Bone Scintigraphy

A 58-year-old man underwent Tc-MDP bone scintigraphy to evaluate the cause of diffuse bone pain. The images did not identify the exact cause of his symptoms. However, a "light bulb"-shaped urinary bladder and diffused increased activity in the scrotal region and left thigh were noted, which suggest a mass effect in the pelvis. A CT scan of the pelvis revealed soft tissue compressing the urinary bladder. A diagnosis of recurrent lymphoma was made.

A New Non-Chemo and Non-Toxic Drug (24-Ethyl-Cholestane- 3&Bgr;, 5&Agr;, 6&Agr;-Triol) with Antitumor Activity in Advanced Refractory or Recurrent, Mainly Aggressive Non-Hodgkin Lymphomas

ABSTRACT Aim: Oxysterols are oxygenated derivatives of cholesterol. Some of these compounds may be toxic and even oncogenic while others seem promising as anticancer drugs. Advanced recurrent or refractory non-Hodgkin lymphomas (NHLs) have a dismal prognosis and are treated palliatively. (24-ethyl-cholestane- 3b,5a,6a-triol) is an oxysterol developed by our group. Besides its high antitumor potential, it has been shown to be devoid of side-effects. Methods: From 2001 to 2013 we have treated 14 patients (pts) suffering from relapsed or refractory non-Hodgkin lymphomas. Eight were males and 6 females. The median age was 50yrs. Eight of these pts were suffering from diffuse large B-cell lymphomas, 2 from lymphoplasmacytic lymphomas, 1 maltoma, 1 diffuse mixed, 1 anaplastic and 1 large T-cell lymphoma. Five pts were stage II (one was 2EB), 4 were stage III and 5 stage IV. Nine pts had B symptoms and 8 other symptoms (pain, neurologic symptoms, dyspnea … ). Except 2 pts, all had previously received 2 to 3 chemotherapy regimens and 5 pts had been treated with radiotherapy. Most of them had a poor performance status. Patients received daily 10 mg/kg of oral (24-ethyl-cholestane- 3b,5a,6a-triol) divided in 3 equal doses every day, until disease progression. Results: Five patients exhibited a complete response (CR), 3 pts had a partial response (PR) 4 pts had a stable disease (NC) and 2 pts progressed under treatment. The median follow-up was 3 years. Most of the pts experienced a rapid (within few days) and dramatic improvement in their quality of life and fast and remarkable all-symptoms control. Some patients taking high doses of pain-killers and or opioids could stop them within 2-4 days. No side-effects of any kind were observed. Conclusions: According to these excellent results, (24-ethyl-cholestane- 3b,5a,6a-triol) seems to be a good candidate for phase II trials in NHLs with or without concurrent chemotherapies or targeted therapies. Disclosure: All authors have declared no conflicts of interest.

Experience of using rituximab for recurrent non-Hodgkin lymphoma in elderly patients of the Orel region

Experience of using rituximab for recurrent non-Hodgkin lymphoma in elderly patients of the Orel region

Frontline Nilotinib Results In Superior Rates Of Molecular Response Versus Imatinib In Chinese Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP): ENESTchina 12-Month Primary Analysis

BackgroundIn global clinical trials, nilotinib has shown superior efficacy vs imatinib for treating patients (pts) with CML-CP. The Evaluating Nilotinib Efficacy and Safety in Clinical Trials–China (ENESTchina) study is assessing the efficacy and safety of frontline nilotinib vs imatinib in Chinese pts with CML-CP. MethodsENESTchina (NCT01275196) is a multicenter, open-label, phase 3 study of Chinese adults with newly diagnosed (≤ 6 mo) CML-CP. Pts were randomized to nilotinib 300 mg BID (n = 134) or imatinib 400 mg QD (n = 133). The primary endpoint was the rate of major molecular response (MMR; ≤ 0.1% BCR-ABL on the international scale) at 12 mo. Molecular assessments were performed at a central laboratory. This analysis was conducted when all randomized pts had ≥ 12 mo of follow-up or discontinued early. ResultsBaseline characteristics were similar between the arms (Table). Most pts (nilotinib, 93%; imatinib, 95%) remained on treatment at the data cutoff. Median actual dose intensities were nilotinib 565 mg/day (range, 167-600 mg/day) and imatinib 393 mg/day (range, 204-550 mg/day). Sixteen pts (nilotinib, n = 9; imatinib, n = 7) discontinued, mainly due to adverse events (AEs; nilotinib, n = 3; imatinib, n = 1), withdrawal of consent (nilotinib, n = 3; imatinib, n = 1), or disease progression (nilotinib, n = 2; imatinib, n = 2).The primary endpoint was met, with a significantly higher rate of MMR at 12 mo in the nilotinib arm vs the imatinib arm (52% vs 28%, respectively; P < .0001). The MMR rate at 12 mo was higher in the nilotinib arm vs the imatinib arm across all Sokal risk groups (Table). The rate of complete cytogenetic response (CCyR) by 6 mo was higher in the nilotinib arm vs the imatinib arm, but by 12 mo CCyR rates were similar in both arms. By the cutoff date, 2 pts (1.5%) in each arm had progressed to accelerated phase/blast crisis (AP/BC) on treatment. Three deaths were reported (all ≥ 28 days after discontinuing treatment), 2 in the nilotinib arm (due to cerebral hemorrhage [n = 1] and study indication [n = 1]) and 1 in the imatinib arm (due to recurrent non-Hodgkin lymphoma).There was no difference between the arms in time to progression to AP/BC on treatment or overall survival.Both drugs were well tolerated, with safety profiles similar to those reported in prior studies. The most common AEs on nilotinib were rash and myalgia; on imatinib, fluid retention and nasopharyngitis were most common (Table). One pt in the imatinib arm had a grade 1 increase in creatine phosphokinase-MB with no clinical signs indicative of ischemic heart disease. No cases of peripheral arterial occlusive disease, ischemic cerebrovascular events, or QTcF > 480 ms were observed in either arm. Newly occurring/worsening grade 3/4 thrombocytopenia and neutropenia occurred at similar rates in both arms, while leukopenia, lymphopenia, and anemia were more frequent in the imatinib arm. The most common newly occurring/worsening grade 3/4 biochemical abnormality in both arms was elevated lipase. ConclusionsIn Chinese pts with newly diagnosed CML-CP, nilotinib was well tolerated and demonstrated superior efficacy over imatinib, as shown by higher rates of MMR in all Sokal risk groups, despite similarly high rates of CCyR after 1 y with both drugs. These results highlight the utility of MMR as a more sensitive efficacy endpoint for differentiating tyrosine kinase inhibitors in pts with CML-CP and provide the first evidence-based, prospective confirmation of the superiority of nilotinib over imatinib observed in the ENESTnd trial. Disclosures:Wang:Novartis: Employment; Bristol Myers Squibb: Consultancy. Baccarani:Ariad: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jevtic:Novartis: Employment, Equity Ownership. Ortmann:Novartis: Employment. Yuan:Novartis: Employment. Menssen:Novartis: Employment. Saglio:ARIAD: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

Urinoma presenting as an abscess in an immunocompromised host: a case report

IntroductionThis case report illustrates the relatively rare occurrence of a urinoma masquerading as an abscess in a patient with refractory recurrent non-Hodgkin’s lymphoma. Although urinomas have been reported after urinary instrumentation, our case was confounded by a concurrent pleural effusion, an immunocompromised host, and clinical appearance and subsequent incision and drainage that was consistent with an abscess. Although not the first case reported in the literature, the constellation of findings in our patient demonstrates the importance of including urinoma in the differential diagnosis of patients with flank mass.Case presentationHere we report a case of a retroperitoneal fluid collection found in an immunocompromised 65-year-old Caucasian woman. She had recurrent non-Hodgkin’s lymphoma and was neutropenic when the collection was found. Drainage of the fluid demonstrated infection, but the case was complicated by increasing fluid production and the development of an ipsilateral pleural effusion. Despite pleural drainage, the abscess output continued to be high. A computed tomography scan demonstrated fluid collection around the renal calices suggestive of rupture; analysis of the fluid was suggestive of a urinoma. The etiology, pathogenesis, and treatment of urinomas in such patients are discussed.ConclusionsUrinomas can present in patients who have had urinary tract instrumentation or trauma, but can occur in other hosts. Patients with hematologic malignancy can develop malignant or sympathetic pleural effusions and are at risk for skin and soft tissue infections. Clinicians caring for immunocompromised patients, particularly hematologists, oncologists, and transplant clinicians, should be aware of this potential complication because rapid identification and attempt at correction are important to optimize outcome.

Treatment of primary CNS lymphoma (PCNSL) following successful treatment of systemic non-Hodgkin’s lymphoma (NHL): a case series

Management of PCNSL occurring after successful treatment of systemic non-Hodgkin's lymphoma (NHL) is poorly defined. Illustrate a treatment approach for PCNSL following prior treatment of a systemic NHL. A retrospective case series of 6 patients (mean age 60 years; range 46-65) diagnosed with a diffuse large B cell lymphoma of the CNS following prior successful treatment of a systemic NHL (low-grade in 2; high-grade in 4). Mean interval to diagnosis of PCNSL after diagnosis of systemic NHL was 12 months (range 7-18). In 4/6 patients in whom genetic analysis could be performed, the PCNSL and NHL differed. Treatment utilized high-dose methotrexate and rituximab (immunochemotherapy) followed in patients with a radiographic complete response by autologous peripheral stem cell transplant (ASCT) with total body irradiation (TBI) and multi-agent conditioning chemotherapy (BEAM: carmustine, etoposide, cytarabine, melphalan). 5/6 patients had a radiographic complete response to immunochemotherapy and were treated with ASCT. 4/5 patients were free of disease following ASCT with a mean follow-up of 3 years (range 0.5-4 years). There were no toxic deaths and all patients transplanted successfully engrafted within 28 days (mean 18). Using a treatment paradigm similar to that utilized for recurrent systemic NHL (induction chemotherapy followed by ASCT) for PCNSL occurring metachronously after successful treatment of systemic NHL appears safe and effective.

Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma

AbstractRecurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although IV rituximab mediates superior disease control of systemic non-Hodgkin lymphoma (NHL), it fails to completely eliminate the risk of meningeal recurrence, likely due to minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy, we conducted the first phase 1 study of intraventricular immunochemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg or 25 mg intraventricular rituximab twice weekly for 4 weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (MTX) during the second treatment each week. More than 150 doses were administered without serious toxicity. In a population with high-refractory CNS NHL, 75% of patients achieved complete cytologic responses and 43% achieved an overall complete response in CSF and/or brain parenchyma. Two patients achieved a first complete response of CNS NHL with intraventricular rituximab/MTX, including 1 with CNS lymphoma refractory to high-dose systemic and intrathecal MTX plus IV rituximab. We conclude that intraventricularrituximab in combination with MTX is feasible and highly active in the treatment of drug-resistant CNS NHL that is refractory or unresponsive to IV rituximab. This trial is registered at www.clinicaltrials.gov as NCT00221325.

Low-Dose Radiotherapy in Patients with Non Hodgkin Lymphoma

AbstractAbstract 4875 Background:Some studies have showed high activity for low-dose radiotherapy (LDRT) in low-grade Non-Hodgkin Lymphoma (NHL). However, this therapeutic approach is often forgotten and other approaches are used - chemotherapy and/or conventional radiotherapy - associated with greater toxicity. The efficacy of total body LDRT (1.5–2 Gy, fractions 0.1–0.25 Gy in 2 – 5 times a week) in disseminated disease is associated with 10 year progression free survival (PFS) of 15 – 25%, with response rates of 70 – 90% (Gérard et al., IJ Radiation Oncology 2010; 78), despite hematologic toxicity and leukemogenic effects. Although its mechanism of action is unknown, its effectiveness has been confirmed (Jones et al., Cancer 1973; 32) suggesting that low dose radiation induces localized lymphocytes apoptosis that can trigger local and systemic benefits. More recently, LDRT was used in palliative treatment for patients with localized disease (4Gy into two fractions, for 3 days) with a low toxicity, and with an objective response (partial or complete) in 24/37 patients, 89% (G Ganem et al., Hematol Oncol1997; 42). Objectives:To assess the response to treatment with LDRT. Explore the predictive factors of response. Determine the progression-free survival (PFS) after LDRT. We will present PFS after LDRT and compare PFS in second line treatment: LDRT vs convencional chemotherapy. Methods:Retrospective study of 44 patients with new or recurrent NHL, treated with LDRT (4Gy in 2 fractions) in 1stor more lines, in a cancer care centre between 2004 and 2011.All transformed lymphomas were excluded (4 patients), as well all diagnosis that weren't centrally reviewed. Patients with complete resolution of the disease according to clinical and/or image studies were considered to have achieved complete response (CR). Results:We identified 40 patients undergoing LDRT, with a median follow-up of 69,5 months after LDRT ([28–87]). 52,5% (n = 21) were male, median age at the time of LDRT was 69 years ([31–85]). 75% of patients (n = 30) had follicular NHL, 12,5% (n = 5) Mantle cell NHL, 10% (n = 4) Marginal Zone NHL and 2,5% (n = 1) lymphoplasmacytic lymphoma.The median numbers of lines of chemotherapy completed before LDRT were 2 lines ([0–5]). There wasn’t any impact on PFS on using Rituximab containing regimens after LDRT (p> 0,05). The overall response rate to LDRT was 92,5% (n = 37): 42,5% (n = 17) achieved complete response (CR), 50% (n = 20) partial response (PR) and 7,5% (n = 3) had disease progression. There weren’t any treatment related toxicities, nor was histological transformation recorded after treatment with LDRT. The logistic regression analysis showed that irradiated areas with dimension <40mm are an independent predictive factor of response (p <0,031, 95% CI [1,268-133,285]). We find a median PFS of 4 months ([0–72]) for patients that went on LDRT, and 50% of these patients relapsed after a median 5 months ([0–35]). 56,5% (n = 13) showed relapse at the same location of the irradiated area. Patients who have completed one chemotherapy scheme after relapsing following LDRT, showed a rate of 6 months-PFS of 50% such as the patients that have done a second LDRT treatment.Concerning follicular NHL patients who relapsed after 1st line conventional chemotherapy, 43,8% (n = 7) were treated with LDRT and 56,2% (n = 9) were treated with conventional 2nd line chemotherapy. Comparing these two groups of patients, there weren’t any difference for PFS for both groups (mean 9,5 vs 9 months p> 0,05, for LDRT vs 2ndline chemotherapy), for equal overall survival. Conclusion:LDRT is an effective treatment for patients with relapsed or recurrent advanced stage NHL. We can obtain high response rates with negligible toxicity. In the treatment of first relapse, PFS is similar when using LDRT or 2nd line chemotherapy. Considering that Rituximab promotes a synergistic effect with LDRT-induced apoptosis and decrease the cell turnover (Skvortsova I et al., J Radiat Res (Tokyo) 2006), comparative studies with conventional chemotherapy regimens should be promoted. Treatment with conventional radiotherapy should be used in patients with relapsed low-stage and localized disease, having curative intention or locally controlling involved areas. Disclosures:No relevant conflicts of interest to declare.

Central nervous system recurrence of systemic lymphoma in the era of stem cell transplantation - an International Primary Central Nervous System Lymphoma Study Group project

Autologous stem cell transplantation has greatly improved the prognosis of systemic recurrent non-Hodgkin's lymphoma. However, no prospective data are available concerning the feasibility and efficacy of this strategy for systemic lymphoma relapsing in the central nervous system. We, therefore, we performed an international multicenter retrospective study of patients with a central nervous system recurrence of systemic lymphoma to assess the outcome of these patients in the era of stem cell transplantation. We collected clinical and treatment data on patients with a first central nervous system recurrence of systemic lymphoma treated between 2000 and 2010 in one of five centers in four countries. Patient- and treatment-related factors were analyzed and compared descriptively. Primary outcome measures were overall survival and percentage of patients transplanted. We identified 92 patients, with a median age of 59 years and a median Eastern Cooperative Oncology Group/World Health Organization performance status of 2, of whom 76% had diffuse large B-cell histology. The majority (79%) of these patients were treated with systemic chemotherapy with or without intravenous rituximab. Twenty-seven patients (29%) were transplanted; age and insufficient response to induction chemotherapy were the main reasons for not being transplanted in the remaining 65 patients. The median overall survival was 7 months (95% confidence interval 2.6-11.4), being 8 months (95% confidence interval 3.8-5.2) for patients ≤ 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic Index for primary central nervous system lymphoma was prognostic for both undergoing transplantation and survival. In conclusion, despite the availability of autologous stem cell transplantation for patients with central nervous system progression or relapse of systemic lymphoma, prognosis is still poor. Long-term survival is, however, possible and more likely in patients able to undergo stem cell transplantation.

Etanercept Therapy for Psoriatic Arthritis in the Presence of Recurrent Non–Hodgkin Lymphoma

Tumor necrosis factor inhibitors (TNFi) have established efficacy in psoriasis and psoriatic arthritis; however, there are concerns regarding the risk of lymphoma with their use. Although current data suggest that this risk is not increased with TNFi treatment, there are no data on the risk of recurrence of previously treated lymphoma under TNFi therapy. Herein, we describe a 46-year-old man with recurrent non-Hodgkin lymphoma whose refractory psoriatic arthritis was effectively treated for 5.5 years with the TNFi etanercept, initiated just 7 months after achieving lymphoma remission, without recurrence of non-Hodgkin lymphoma. However, he subsequently died 6.5 years later of pancreatic adenocarcinoma.

Treatment of Primary CNS Lymphoma (PCNSL) Following Successful Treatment of Systemic Non-Hodgkins Lymphoma (NHL) (P04.186)

Objective: Illustrate a treatment approach for PCNSL following successful treatment of a systemic NHL. Background Treatment of PCNSL occurring after successful treatment of systemic NHL is ill defined. Design/Methods: A retrospective case series of 6 patients (mean age 60 years; range 46-60) diagnosed with a diffuse large B-cell NHL of the CNS follwing prior successful treatment with a systemic NHL (low grade in 2; high grade in 4). Mean interval to diagnosis of PCNSL after diagnosis of systemic NHL was 12 months (range 7-18). In 4/6patients in whom genetic analysis could be performed, the PCNSL and NHL differed. Treatment utilized high-dose methotrexate and rituximab followed in patients with a radiographic complete response by autologous peripheral stem cell transplant (PSCT) with total body irradiation and multiagent conditioning chemotherapy (BEAM). Results: 5/6 patients responded to immunochemotherapy and were treated with PSCT. 4/5 patients were free of disease following PSCT with a mean follow-up of 2 years (range 0.5-4 years). There were no toxic deaths and all patients transplanted successfully engrafted. Conclusions: Using a treatment paradigm similar to that utilized for recurrent systemic NHL (induction chemotherapy followed by autologous PSCT), PCNSL occuring metachronously after successful treatment of systemic NHL appears safe and effective. Disclosure: Dr. Chamberlain has received personal compensation for activities with Sigma-Tau, Genentech, Inc., Roche Diagnostics Corporation, Myriad, and Schering-Plough Corporation. Dr. Chamberlain has received compensation for serving on the boards of Genentech/Roche, Sigma Tau/Enzon, and Myrexis/Myriad. Dr. Chamberlain has received research support from Exelixis, MedImmune, NCCN, and Northwestern University/Genentech, Inc.