Nodal non-Hodgkin's Lymphoma Research Articles

P1089: BRENTUXIMAB VEDOTIN, NIVOLUMAB, DOXORUBICIN, AND DACARBAZINE (AN+AD) FOR ADVANCED STAGE CLASSIC HODGKIN LYMPHOMA: PRELIMINARY SAFETY AND EFFICACY RESULTS FROM THE PHASE 2 STUDY (SGN35 027 PART B)

Background: Brentuximab vedotin (BV) and nivolumab are both active and well-tolerated in patients (pts) with classical Hodgkin lymphoma (cHL) and were previously studied in first salvage (overall response rate [ORR] 85%; complete response [CR] 67%) (Advani 2021) and as firstline (1L) therapy in older adults (ORR 95%; CR 79%) (Yasenchak 2019). The combination of BV plus nivolumab demonstrated promising activity as a frontline treatment option for pts over 60 yrs of age with cHL (Friedberg 2018). Additionally, in pts with non-bulky Stage I or II cHL, treatment with BV plus doxorubicin and dacarbazine (AD) resulted in a CR rate of 97% at end of treatment (EOT), as well as a promising 4-year progression-free survival (PFS) estimate of 91%. There were no cases of ≥Grade 3 peripheral neuropathy and only 9% were Grade 2 (Abramson 2021). Aims: This abstract will present the preliminary safety and efficacy results from Part B of the SGN35-027 study, which enrolled pts with Ann Arbor Stage II cHL with bulky mediastinal disease (defined as a single node or nodal mass ≥10 cm as determined by CT imaging), or Stage III or IV cHL. Methods: SGN35-027 (NCT03646123) is an open-label, multiple part, multicenter, phase 2 clinical trial. Pts received up to 6 cycles of AN+AD (consisting of BV 1.2 mg/kg, nivolumab 240 mg, doxorubicin 25 mg/m2, and dacarbazine 375 mg/m2). All study drugs were administered by IV infusion on Days 1 and 15 of each 28-day cycle. The primary endpoint was CR rate at EOT. Key secondary endpoints included safety, tolerability, ORR, and PFS. Disease response and progression was assessed by investigators using the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin Lymphomas (Cheson 2014) and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016) at Cycle 2 and EOT. Results: In Part B, 58 pts were enrolled and 57 pts received at least 1 dose of study treatment. Of these 57 pts, 30 (53%) were male, 27 (47%) were female, 50 (88%) were white, 46 (81%) were not of Hispanic or Latino/a or Spanish origins, and 54 (95%) were <65 years old. Median age was 35 yrs (range: 19-78 yrs); 30% had Stage II cHL with bulky mediastinal disease, while 18% and 51% had Stage III and IV cHL, respectively. Of 58 pts enrolled, 52 (90%) completed treatment and 4 (7%) discontinued due to AEs. The most frequently reported TEAEs were nausea, fatigue, and diarrhea (70%, 51%, and 46% of pts, respectively). Grade 3 or higher TEAEs were reported in 30 pts (53%), with neutropenia and increased ALT in 5 pts (9%) being the most frequent. Treatment-related AEs occurred in 98% of pts; the most frequent were nausea, fatigue, and peripheral sensory neuropathy (65%, 46%, and 39% of pts, respectively). Treatment-related SAEs occurred in 8 pts (14%), of which pneumonitis was the most common (3 pts [5%]). Immune-mediated AEs were observed in 18 pts (32%), and hypothyroidism (4 pts [7%]) was the most frequently reported. No febrile neutropenia was observed, and there were no Grade 5 AEs. Preliminary results show at EOT, 52 pts had a response to treatment (ORR 93% [95% CI:82.7-98.0]), with 49 pts having a complete response (CR rate: 88% [95% CI: 75.9-94.8]). Summary/Conclusion: Preliminary results demonstrate that AN+AD has promising clinical activity and is well-tolerated, with no new safety signals observed. The omission of bleomycin and vinblastine may have contributed to the absence of certain AEs, such as febrile neutropenia. AN+AD may provide another active treatment option for patients with 1L advanced cHL.

SIL-2R: A Novel Diagnostic Biomarker for Primary Adrenal Lymphoma.

Primary adrenal lymphoma (PAL) is difficult to distinguish from other adrenal masses. Soluble interleukin-2 receptor (sIL-2R) is a diagnostic biomarker for nodal non-Hodgkin lymphoma, whose association with PAL is unknown. The aim of this study was to determine the diagnostic utility of serum sIL-2R for Patients with PAL. Prospective cohort study. A total of 118 patients with adrenal masses who were willing to be tested for levels of serum sIL-2R from a tertiary hospital between 2019 and 2021 were included. Serum sIL-2R and lactate dehydrogenase (LDH) levels. Patients with PAL had significantly higher sIL-2R levels than those of patients with other adrenal masses with indetermined and benign computed tomography (CT) features (both Ps < 0.001). The LDH levels of patients with PAL were also significantly higher than those of patients with other adrenal masses with indeterminate and benign CT features (both Ps < 0.001). Good discrimination of patients with PAL from other patients (PAL vs other adrenal masses with indeterminate CT features/non-PAL) was achieved with an area under the receiver operating characteristic curve (AUC) of 0.984 (95% CI, 0.95-1)/0.992 (95% CI, 0.975-1.000) using the serum levels of sIL-2R and further improved (AUC = 0.998, 95% CI, 0.994-1.000; AUC = 0.999, 95% CI, 0.996-1.000) after adjusting by LDH category. For the first time, we have identified that serum sIL-2R and LDH category-adjusted sIL-2R levels have good diagnostic performances for PAL.

PRIMARY CNS LYMPHOMA MIMICKING TUBERCULOSIS INFECTION - A CASE REPORT

Primary central nervous system lymphoma (PCNSL) is a rare variety of extra nodal non-Hodgkin lymphoma that reportedly involves leptomeninges, the brain, spinal cord, eyes, or may involve other organs systemically. We present a case of 46-yearold woman with complaints of headache and fever for three weeks, associated with right-sided weakness &amp; altered state of consciousness for one week. The most common presentation of primary central nervous lymphoma is diffuse or multifocal supratentorial masses causing cognitive deterioration and involvement of vitreous, retina, and optic nerve. Most cases ofPCNSL are left undiagnosed due to uncommon

Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Advanced Stage Classic Hodgkin Lymphoma: Preliminary Safety Results from the Single-Arm Phase 2 Study (SGN35-027 Part B)

Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Advanced Stage Classic Hodgkin Lymphoma: Preliminary Safety Results from the Single-Arm Phase 2 Study (SGN35-027 Part B)

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Brentuximab Vedotin in Combination with Lenalidomide and Rituximab in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (ECHELON-3, Trial in Progress)

BackgroundThe majority of patients with relapsed/refractory (R/R) DLBCL who relapse after hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy, or who are not candidates for HSCT or CAR-T, have poor outcomes and need novel therapies (Crump 2017). Brentuximab vedotin (BV) was the first antibody-drug conjugate to be approved in multiple cancer types (Gauzy-Lazo 2020). The combination of a CD30-directed monoclonal antibody, a protease-cleavable linker, and the microtubule-disrupting agent monomethyl auristatin E drives the anticancer activity of BV by inducing cell cycle arrest and apoptosis (Sutherland 2006). Lenalidomide may enhance the activity of BV through immune-mediated mechanisms. In a phase 1 trial (NCT02086604) in which 37 patients with R/R DLBCL were treated with BV + lenalidomide, the objective response rate (ORR) was 56.7% (73.3% in CD30+ patients). The median duration of remission was 13.2 months in patients with a complete response (CR) or partial response (PR) and 11.7 months in patients with a CR, PR, or stable disease (SD) >6 months. The median progression-free survival (PFS) and overall survival (OS) were 10.2 months and 14.3 months, respectively, and results were similar in the CD30+ and CD30 <1% groups (manuscript submitted). The clinical activity and manageable safety profiles of BV, lenalidomide, and rituximab as single agents provide a strong rationale for this combination in multiple relapsed and heavily pretreated patients with R/R DLBCL.Study Design and MethodsECHELON-3 (NCT04404283) is a randomized, double-blind, placebo-controlled, active-comparator, multicenter phase 3 study designed to evaluate the efficacy of BV versus placebo, in combination with lenalidomide and rituximab, in patients with R/R DLBCL.Key eligibility criteria will include patients ≥18 years of age with R/R DLBCL with an eligible subtype, ≥2 prior lines of systemic therapy and ineligible for stem cell transplant or CAR-T therapy, Eastern Cooperative Oncology Group performance status 0 to 2, fluorodeoxyglucose-avid disease by positron emission tomography (PET), and bidimensional measurable disease of at least 1.5 cm by computed tomography (CT). Patients with a history of another malignancy within the past 2 years, any uncontrolled Grade ≥3 infection, Grade ≥2 peripheral neuropathy, or previous exposure to BV or lenalidomide will not be eligible.After completing the safety run-in period, patients (n=400) will be randomized 1:1 to receive either BV (1.2 mg/kg intravenously every 3 weeks [Q3W]) or placebo (intravenously Q3W) in combination with lenalidomide (20 mg orally daily) and rituximab (1400 mg subcutaneously Q3W from Cycle 2, with 375 mg/m 2 intravenously on Cycle 1 Day 1). Treatment may continue while there is clinical benefit (SD or better) without progression or unacceptable toxicity. Patients will be stratified by CD30 expression (≥1% [positive] vs <1% [negative]), prior allogeneic or autologous stem cell transplant therapy (received or not), prior CAR-T therapy (received or not), and cell of origin (germinal center B-cell [GCB] or non-GCB).The dual primary endpoints are PFS per blinded independent central review (BICR) in the intention-to-treat (ITT) and CD30+ populations. Key secondary endpoints are OS in the ITT and CD30+ populations, and ORR per BICR. Other secondary endpoints include CR rate, duration of objective response, and safety and tolerability of the combination. Disease response will be assessed by BICR and the investigator according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014). Radiographic disease evaluations, including contrast-enhanced CT and PET, will be assessed at baseline, then every 6 weeks from randomization until Week 48, then every 12 weeks thereafter. PET is not required after CR is achievedFor the analyses of PFS per BICR, the stratified log-rank test will be used to compare PFS between the 2 treatment groups. Hazard ratios will be estimated using the stratified Cox regression model. PFS will also be summarized using the Kaplan-Meier method. Similar methods will be used to estimate OS and other time-to-event efficacy endpoints.The study is currently enrolling and will be open in 16 countries. DisclosuresBartlett: Merck: Research Funding; Kite, a Gilead Company: Research Funding; Janssen: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Autolus: Research Funding; Seagen: Consultancy, Research Funding; Roche/Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Millennium: Research Funding; Pharmacyclics: Research Funding. Yasenchak: Seagen Inc.: Research Funding. Harwin: Sarah Cannon Research Institute: Other: Grants, Research Funding. Sims: Seagen Inc.: Current Employment. Nowakowski: Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene, NanoString Technologies, MorphoSys: Research Funding.

Characteristics, Management and Outcomes of Patients with Intravascular Lymphoma: A Mayo Clinic Experience

Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL.Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method.Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was <2 in 66%.The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse.Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (>30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29].Conclusion:1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected.2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations.3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions.4.Overall prognosis in the literature was poor with most patients surviving <1 year. Our cohort has mOS of 57 months. The reason(s) for better survival in our cohort could not be definitively determined.5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size.6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL.7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. [Display omitted] DisclosuresNowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

S2051 Primary Esophageal Lymphoma or Lymphoma Presenting as an Esophageal Mass: Rare Disease or Rare Presentation of a Disease?

Introduction: GI tract is the most common site of extra nodal non Hodgkin lymphoma (NHL) with the usual sites being stomach, small intestine and colon. Esophageal involvement has been reported in < 1% of cases and mostly occurs as an extension of mediastinal or gastric lymphoma. Here, we present a case of diffuse large B cell lymphoma (DLBCL) presenting with obstructive esophageal symptoms and diagnosed on esophageal ulcer biopsy. Case Description/Methods: A 72-year-old White male with history of 84 pack years smoking, GERD, presented with a month of shortness of breath, dysphagia to solids, odynophagia, loss of appetite, and 20 lbs. weight loss. Labs revealed WBC count 7000/µL. CT chest without contrast showed a large mediastinal mass with hilar extension, causing esophageal obstruction and two masses within the right lobe of liver. Endoscopy showed a mid-esophageal ulcer without bleeding, and atypical lymphoid cells on biopsy. Immunohistochemistry was positive for CD20, PAX5, BCL2 and BCL6, MUM1 and negative for CD10, cyclinD1 with MIB1 90%, thus consistent with DLBCL. Biopsy of liver mass showed similar histology and immunohistochemistry. HIV testing was negative. He was started on EPOCH based chemotherapy for the DLBCL. On chart review, CT Lung screening a year ago showed several filling defects in mid esophagus, however the filling defects were not evaluated as he was lost to follow up. Discussion: Primary esophageal DLBCL is a rare NHL with only handful of cases reported in literature to date. Our patient did not satisfy Dawson’s criteria for diagnosis of primary GI lymphoma which requires absence of peripheral and mediastinal lymphadenopathy, lack of liver and spleen involvement, and normal peripheral blood count. However, the utility of Dawson’s criteria for diagnosis of primary esophageal lymphoma has been questioned. Esophagus is a mediastinal structure and has rich lymphatic network, thus, predisposing to early mediastinal lymph nodes involvement. Also, esophageal cancers have been known to spread to liver via venous channels. Our patient had several mid esophageal filling defects a year ago and now presented with a large mediastinal mass encasing esophagus, thus, supporting the diagnosis of primary esophageal lymphoma. This case highlights the importance of endoscopic evaluation of esophageal filling defects seen on imaging.Figure 1.: Low dose CT lung screening performed a year prior shows filling defects in mid esophagus (red arrow) as seen in (A) axial section and (B) sagittal section. (C) CT chest without contrast on presentation showing large mediastinal mass, at the same level as image A causing esophageal obliteration. (D) Endoscopic biopsy of esophageal ulcer showing atypical lymphoid cells.

Prognostic significance of immunohistochemical markers in Primary CNS lymphomas

Primary CNS lymphoma (PCNSL) is a rare form of extra nodal Non-Hodgkin Lymphoma that is typically confined to the brain, spinal cord, lepto meninges and eyes. We studied the clinico pathological features of PCNSLs, immuno histochemical (IHC) markers expressed and the association of morphological features &amp; IHC markers with clinical outcome. 30 cases of primary CNS lymphomas were studied. 25 cases were diffuse large B cell lymphomas, which were sub classified using Hans algorithm into GCB and non-GCB. The IHC markers done were CD20, CD3, BCL2, BCL6, MUM-1, CD10 and c-myc. Mean proliferation index Ki was 80%. Follow up and survival data was collected and the association of each IHC marker and subtype with prognosis was assessed. PCNSL forms around 2% of all lymphomas as well as primary CNS tumours. Non GCB type is more common (72%). Mean overall survival was 9.7 months. Ki-67 index of 80% or more is the only independent variable of prognostic significance. None of the other IHC markers or sub typing had any influence on the outcome.

Diagnosis and prognostic stratification of cutaneous lymphoma.

Primary cutaneous lymphomas are a heterogenous group of non-Hodgkin's lymphoma of both T/natural killer-cell and B-cell origin and defined to primarily present in the skin without extracutaneous involvement at diagnosis. In contrast to nodal non-Hodgkin's lymphoma, cutaneous T-cell lymphomas (CTCL) are more generally seen than cutaneous B-cell lymphomas (CBCL). CTCL and CBCL have various subtypes and each subtype has specifically characteristic clinical, pathological, and prognostic features. The diagnostic methods and staging evaluation of cutaneous lymphomas is mostly common in various guidelines created by professional societies. The diagnosis is made comprehensively based on clinical, pathological, laboratory, radiological, and genetic findings. On the other hand, definite prognostic stratification has not been completely established yet in most cutaneous lymphomas. This article focuses on the general and novel diagnostic methods and the current findings about prognostic factors and stratification in cutaneous lymphomas.

Nanomedicine Applications in Treatment of Primary Central Nervous System Lymphoma: Current State of the Art.

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive subtype of extra nodal non-Hodgkin lymphoma (NHL), which is confined in the central nervous system (CNS). Despite recent advancements in treatment options, the overall prognosis of PCNSL remains poor. Among many unfavorable factors affecting efficacy, inadequate drug delivery into the CNS is still the thorniest challenge. Blood-brain barrier (BBB) constitutes a significant impediment, restricting entry of most therapeutics to the brain. Nanotechnology has offered great promise for brain diseases, as various nano-based drug delivery systems (NDDSs) have been developed for delivery of theranostic agents in to the CNS. These drug delivery systems possess significant advantages, including good feasibility, reliable safety profile, excellent BBB penetration and potent antitumor effects. As for treatment of PCNSL, numerous well-developed BBB-crossing nano-based strategies can be applied with proper modifications and improvements. Some exquisitely designed NDDSs specific for PCNSL have shown great potential. In this review, we provide a summary on current status of diagnosis and treatment of PCNSL, followed by an overview of BBB-crossing strategies applied in management of PCNSL, both novel and wellestablished. Finally, challenges and future perspectives in this field are also discussed.

Discovery of HBW-3-20, the first potent reversible inhibitor of Bruton’s tyrosine kinase (BTK) with high brain exposure.

e15068 Background: It has been an on-demand task to develop a BTK inhibitor of significant brain exposure, a critical property for extending its usages to treat Primary Central Nervous System Lymphoma (PCNSL) and autoimmune disorders. PCNSL is an aggressive extra nodal non-Hodgkin lymphoma that exclusively invades the central nervous system (CNS). Tirabrutinib, an irreversible BTK inhibitor with limited brain exposure, is the first BTK inhibitor approved for the treatment of recurrent or refractory primary central nervous system lymphoma recently. PRN2246 is another irreversible BTK inhibitor claimed to be of brain exposure, and is currently in clinical trials for the treatment of multiple sclerosis. Methods: New reversible BTK inhibitors were designed, synthesized and tested for enzymatic activities against wild-type and C481S-mutated BTK. Highly active compounds were confirmed for growth effects in diffuse large B-cell lymphoma derived TMD8 cells. Their microsomal stability and ADME properties were also assessed. Potent and bioavailable compounds were further measured for brain exposures in rats. Results: HBW-3-20 has excellent potency against both wild-type and C481S-mutated BTK, with IC50 of 2.5 and 3.8 nM, respectively. Its TMD8 cellular potency is 72 nM. In a head-to-head direct comparison of brain exposure experiment, HBW-3-20, tirabrutinib and PRN2246 were all dosed at 10mg/kg orally. The brain and plasma concentration were measured after 1 hour and the data are shown in the table below. The brain to plasma ratio for HBW-3-20, tirabrutinib and PRN2246 are 58%, 11.8% and 4.2% respectively. Our results show that HBW-3-20 has much greater brain permeability than tirabrutinib or PRN2246 in rats. Conclusions: HBW-3-20 is the first potent reversible BTK inhibitor that shows promisingly high brain permeability. HBW-3-20 provides a very valuable clinical candidate for treating B-cell malignancies in brain and autoimmune disorders![Table: see text]

Coexistence of Endometrial Cancer and Nodal Non-Hodgkin Lymphoma: A Case Series

Background: Synchronous and metachronous tumors are a unique entity. In the setting of endometrial cancer, most concomitant primary sites include ovarian, colon, and breast cancer. The coexistence of endometrial and hematologic malignancies is rare, with only seven cases reported in the literature. Over a time interval of 10 years, we have encountered this unusual condition in seven patients of our own. This is the most extensive case series published on concurrent hematologic and endometrial malignancies. Methods: Retrospective chart review from 2002 to 2012 was performed. Results: Our patients were referred to a gynecologic oncology office from the years 2002 to 2012 due to endometrial cancer. They underwent surgical diagnoses and staging for endometrial carcinoma. Hematopoietic neoplasms were incidentally diagnosed when histologic analysis of the lymph nodes was performed. The finding of significantly enlarged lymph nodes was described in the operative reports of five out of seven patients. Conclusions: As clinicians, it is crucial to be aware of the various pathologies that can affect cancer survivors, including multiple primary malignancies. Clinical presentation, imaging and intraoperative findings of the most common neoplasms could have a positive impact on patient care. (J GYNECOL SURG 37:479)

Histomorphological and Morphometric Evaluation of Microvessel Density in Nodal Non-Hodgkin Lymphoma Using CD34 and CD105.

Background Expression of angiogenic markers determined by microvessel density (MVD) could be used as a reliable predictor of prognosis and as a potential target for antiangiogenic therapy in different categories of non-Hodgkin lymphoma (NHL). Aims The aim of this study was to evaluate MVD using immunohistochemical methods and computer-assisted quantitative image analysis in nodal NHL patients and compare CD34 and CD105 expression in lymph nodes of NHL patients. Materials and Methods The present study was conducted on 60 lymph node biopsies received in the Department of Pathology at our tertiary care center for histopathological examination. Representative paraffin-embedded tissue sections were stained with hematoxylin and eosin along with immunohistochemical stains for CD34 and CD105. MVDs were analyzed at 400× using automated image analyzer by two investigators independently. Statistical Analysis Data were calculated, tabulated, and statistically analyzed using SPSS (Statistical Package for Social Studies) statistical program version 18. The values entered were mean of morphometric parameters. In all tests, p -values below 0.05 were regarded as significant. Results MVD was determined by CD34 and CD105 antibody highly correlated with different categories of NHL. Higher MVD was observed in cases of aggressive NHL as compared with indolent NHL and the difference was statistically significantly. MVD using CD105 was correlated more strongly as compared to CD34 with different categories of NHL. Conclusion The present study concluded that NHL exhibits potent angiogenic activity that increased significantly with increasing aggressiveness. The study also demonstrated that CD105 is more specific than CD34 as a marker of neoangiogenesis in NHL.

Uterine non-Hodgkin lymphoma: a case report and review of literatures

&lt;p&gt;&lt;span&gt;Primary extra nodal non-Hodgkin lymphomas of the genital tract are uncommon, and involvement of the uterine corpus is not only extremely rare but lacks pathognomonic signs and symptoms, resulting in delayed diagnosis and treatment. This prompted this case report of a multiparous lady who presented with recurrent bleeding per vaginam and progressive abdominal swelling that was initially suspicious of being uterine sarcoma, but histological analysis of excised sample was diagnostic of non-Hodgkin lymphoma of the uterus. The report also highlights the challenges to diagnosis and management in a resource poor setting where advanced diagnostic aids are not readily accessible. The diagnosis of uterine non-Hodgkin lymphoma, though uncommon, should be considered in any patient with an abdominal/pelvic mass and/or abnormal bleeding per vaginam. &lt;/span&gt;&lt;/p&gt;

Extranodal non-Hodgkin’s lymphoma: A case series at a tertiary care hospital

To study and findings in a case series of Extra Nodal Non Hodgkin Lymphomas (EN NHL). 17 cases of primary, collected during a period of November 2019 to November 2020 (one year), wherein the clinical data included age, gender, site, clinical presentation and findings were collected and staining was done along with (IHC) using a panel of antibodies depending on the morphology.17 cases of primary taken. Majority of our patients were from higher age group, presenting in sixth decade, though the age range was wide between 5-92 years. Our study included 12 males and 5 females, with a male: female ratio of 2.4:1. We found masses and GIT as the most common site for. Weight loss followed by fever was the most common clinical presentation in our study presentation. Ann Arbor Staging was done in 16/17 cases where 35% (6/17) belonged to stage I, 35% (6/17) cases belonged to stage II, 17.6 (3/17) belonged to stage III and 1.5% (1/17) belonged to Eastern cooperative oncology group performance scale (ECOG) was also calculated and documented. This study highlights importance of diagnosing Non Hodgkin’s lymphomas as a separate entity since its clinical presentation, prognosis, staging and management differs from Nodal NonHodgkins lymphoma.

Primary Diffuse Large B-cell Lymphoma of the Breast: Treatment and Long-Term Outcome of Two Cases

AbstractPrimary breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin’s lymphoma (NHL). It accounts for &lt;0.5% of all breast malignancies and 2% extranodal NHL. Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype. We report three cases of PBL diagnosed and treated at our center. The clinical records of three female patients diagnosed with PBL from 2004 to 2015 were reviewed. Two patients had DLBCL, and the third patient had anaplastic large cell (ALCL) NHL. The mean age at presentation was 56 years. One patient with DLBCL was treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy and the second patient with rituximab plus CHOP chemotherapy. Both the patients showed complete response and have had a disease-free survival of 84 and 96 months, respectively. The third patient with ALCL refused further treatment after confirmation of diagnosis. PBL-DLBCL can be successful treated with chemotherapy, and long-term survival is similar to nodal NHL.

Brentuximab Vedotin in Combination with Nivolumab, Doxorubucin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma

Brentuximab Vedotin in Combination with Nivolumab, Doxorubucin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma

Histo-morphologic Spectrum of Non-Hodgkin Lymphoma According to WHO Classification 2016: A Cross-Sectional Study

Background: Geographic variations with regard to incidence and histological subtypes are known to occur in Non-Hodgkin lymphoma (NHL). This study was aimed to see the incidence and subtypes of NHL in a group of Bangladeshi population.Methods: This cross sectional study was carried out in Armed Forces Institute of Pathology (AFIP) Bangladesh, from 1st April 2017 to 31st March 2018. All nodal and extranodal tissues which were morphologically diagnosed as NHL were included in the study and immunohistochemistry was done for sub-classification according to WHO classification 2016. Bone marrow trephine biopsy samples were excluded.Results: Total cases: 106, mean age: 48.5 years ± 18.5 (range 2Y 9 M –82 years), male-female ratio: 2.2:1. Total subject of B cell Lymphoma (BNHL): 83 (78.3%) and T cell lymphoma (TNHL): 23 (21.7%). Among BNHL, total subjects of diffuse large B cell lymphoma (DLBCL) 50 (60%), follicular lymphoma 9 (11%), marginal zone lymphoma 8 (10%), small cell lymphoma and mantle cell lymphoma 5 (6%) each, Burkitt lymphoma 4 (5%) and B cell lymphoblastic lymphoma 2 (1.89%) in number. Among TNHL peripheral T-cell lymphoma NOS 11 (48%), anaplastic large cell lymphoma (ALCL) 5 (22%), T cell lymphoblastic lymphoma 4 (17%), and angio-immunoblastic T cell lymphoma 3 (13%) in number. Among 5 ALCL, 4 ALK positive and 1 ALK negative. Number of primary extra-nodal NHL were 29 (27%) with most common involved organ system being GIT and most common histological subtype being DLBCL.Conclusion: Quite similar pattern of age range with mean age, male to female ratio, subtypes and extra nodal NHL distribution prevailing in our subcontinent is found in our population with subtle increased incidence of TNHL indicating the necessity of further large epidemiological study.Birdem Med J 2018; 8(3): 215-222

Primary Cutaneous Lymphomas; A review of a rare but diverse cutaneous tumour

Title: Primary Cutaneous Lymphomas; University of Benin Teaching Hospital Experience Introduction: Primary cutaneous lymphomas (CLs) are a heterogeneous group of extra nodal non-Hodgkin lymphomas (NHL) which are confined to the skin at diagnosis. The skin is the second most common site of extra nodal lymphoma. They are rare tumours accounting for 18% of cases of extra nodal NHL. The goal of this study is to determine the prevalence of primary cutaneous lymphomas at the University of Benin, Teaching Hospital, Benin City, Edo State, Nigeria, vis-a-vis reviewing the existing literature on the subject matter. Methodology: A 10-year retrospective study of primary CLs seen in UBTH from January 2004- December 2013. Skin biopsies were received fixed in 10% formalin in the laboratory unit of the Department of Morbid Anatomy, UBTH, processed in paraffin wax, sectioned and stained with Haematoxylin and Eosin. Histology slides were retrieved, studied and lesions characterized. Result: There were 375 cases of histologically diagnosed cutaneous tumours. The ages of the patients in this study ranged from 1 to 111 years. Their mean age was 38.32 years (SD = 19.38. There were 192 females (51.2%) and 183 males (48.8%) giving a female to male ratio of 1.05:1. Keratinocytic tumours were the most common lesions seen. There was no case of primary cutaneous lymphoma seen in this study giving a prevalence of 0%. Discussion: Primary CLs are rare tumours. Previous studies in Nigeria and Ghana like the index study did not report a case of CLs. This is unlike the report from Lagos, Nigeria where CLs have been reported. So by extension, although CLs are rare we should not foreclose the possibility of finding isolated cases in our environment. Conclusion: We align with the submission of Bradford et al that further investigations using large populations and molecular tools are warranted to elucidate the aetiology of the diverse spectrum of CLs. Despite this, we trust without prejudice that case reports and institutional base studies as invaluable means in the gathering of data, especially for rare tumours like CLs.