scholarly journals Intrathecal (IT) Chemotherapy for Central Nervous System (CNS) Prophylaxis in Diffuse Large B-Cell Lymphoma (DLBCL): A Single Centre Retrospective Observational Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Luke Attwell ◽  
Benjamin Gray ◽  
Rachel Hall ◽  
Sally Killick ◽  
Helen McCarthy ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Educational Meetings ◽  
Large B Cell

Introduction: CNS relapse of DLBCL is associated with poor prognosis. Estimated incidence varies between 1.9 and 8.4%1. The CNS-International prognostic index (IPI)2 help risk stratify and estimate the 2-year risk of CNS relapse in DLBCL patients treated with R-CHOP chemotherapy. CNS prophylaxis is indicated in patients with a high risk of CNS relapse (a score of ≥4 equated to a 10.2% risk). High-risk DLBCL patients outside the CNS-IPI system include double/triple-hit (MYC/BCL-2/BCL-6 translocations) lymphoma, HIV lymphoma, testicular lymphoma, primary cutaneous lymphoma-leg type, stage IE breast lymphoma3. IT methotrexate or cytarabine administered during the course of systemic chemotherapy has been the most widely employed method of CNS prophylaxis but there is paucity of data validating its efficacy. Aim: The primary aim of the study was to evaluate the CNS relapse rates in DLBCL patients who received CNS prophylaxis. Patients and Methods: This was a single-centre retrospective observational study conducted in a district general hospital. Data was extracted from the regional (Dorset Cancer Network) DLBCL database and laboratory reports for CSF analysis at the time of the first intrathecal chemotherapy. Medical records of patients with DLBCL who received CNS prophylaxis were evaluated for the following patient-related and disease-related demographics: age at diagnosis, gender, stage, systemic treatment, CNS prophylaxis, treatment response, remission duration, systemic relapse rates, CNS relapse rates and survival. CNS-IPI scores were retrospectively calculated and additional indications evaluated for patients who received CNS prophylaxis. Results: Between 2013 and 2018, 178 patients were diagnosed with DLBCL. All patients were treated with RCHOP chemo-immunotherapy. CNS prophylaxis was administered in 47 (26%) patients. Median age was 69 years (range 20-86 years) and 62% were males. All 47 patients (100%) received IT methotrexate as CNS prophylaxis, with 43 (91%) receiving all of the planned 4 doses of IT methotrexate 12.5 mg each. A CNS-IPI score of ³4 was present in 31 (66%) patients, and a score of 2-3 in 9 (19%) patients. Additional risk factors identified included testicular lymphoma in 3 patients, breast lymphoma in 2 patients and oropharyngeal lymphoma in 2 patients. Ten (21%) patients received their treatment at the outset with courses 1-4 of R-CHOP. Of the 47 patients who received CNS prophylaxis, 5 (10%) relapsed; all had isolated CNS lymphoma at relapse. Median time to CNS relapse was 25 months (range 12-36 months) from initial diagnosis of DLBCL. Median survival after CNS relapse was 5 months (range 2-9 months). Of the remaining 141 patients, 2 patients relapsed with isolated CNS lymphoma. Conclusion: Although the overall incidence was low (4%), CNS relapse was observed in 10% of high-risk patients all of whom received CNS prophylaxis with IT methotrexate. The efficacy of CNS prophylaxis with IT chemotherapy remains unproven. There is no randomised study to show that IT prophylaxis alone is effective. Current British guidelines recommend high-dose intravenous methotrexate over IT methotrexate if patient's physiological fitness and renal function are acceptable4. The median age in our cohort was 69 years which makes it challenging to deliver dose-intensive systemic therapy concurrently with intravenous high-dose methotrexate. The role of CNS prophylaxis in high-risk patients including its efficacy and safety in older patients need further evaluation in prospective randomised studies. References Eyre T et al.Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review. Hematologica. 2019;105(7):1914-1924.Norbert Schmitz et al.CNS International prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOPJ Clin Oncol 2016; 34:3150-3156.Andrew D Zelenetz et al.National Comprehensive Cancer Network (NCCN) Guidelines: B-Cell Lymphomas.Version 2.2020.Pamela McKay et al.The prevention of central nervous system relapse in diffuse large B-cell lymphoma: a British Society for Haematology good practice paper. Onlinelibrary.wiley.com. 2020. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16866 Disclosures Hall: Janssen:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Karyopharm:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Takeda:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings.Killick:Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Jazz Pharmaceuticals:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Gilead:Honoraria, Other: Support for attending education meetings.McCarthy:Janssen:Honoraria;Abbvie:Membership on an entity's Board of Directors or advisory committees.Walewska:AbbVie:Other: sponsored for educational meetings, Speakers Bureau;Janssen:Other: sponsored for educational meetings, Speakers Bureau;Gilead:Speakers Bureau;Astra Zeneca:Membership on an entity's Board of Directors or advisory committees.Chacko:Astellas:Honoraria;Daiichi-Sankyo:Honoraria;Novartis:Honoraria, Other: Travel Grants;Gilead:Other: Travel grants;Jazz Pharmaceuticals:Other: Travel grants;Celgene:Other: Travel grants.

scholarly journals Safety of Axicabtagene Ciloleucel CD19 CAR T-Cell Therapy in Elderly Patients with Relapsed or Refractory Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 96-96 ◽  
Author(s):  
Dahlia Sano ◽  
Loretta J. Nastoupil ◽  
Nathan H. Fowler ◽  
Luis Fayad ◽  
F. B. Hagemeister ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Age Groups ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

Abstract Background Axicabtagene ciloleucel (axi-cel) is an autologous CD19-specific CAR T-cell therapy product that was FDA approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy. In the pivotal ZUMA-1 study, the best overall response (ORR) and complete response (CR) rates observed in 108 patients treated with axi-cel were 82% and 58%, respectively. At a median follow-up of 15.4 months, 42% of the patients remain in ongoing response (Neelapu et al. N Eng J Med 2017). Analysis of efficacy outcomes in patients <65 years (N=81) and ³65 years (N=27) showed that the ORR and ongoing response at 12 months were comparable between the two subgroups (Neelapu et al. N Eng J Med 2017). Whether the safety is also comparable between the two subgroups is unknown. Here, we report safety outcomes in elderly patients (³65 years) with large B-cell lymphoma treated with axi-cel at our institution. Methods We retrospectively analyzed and reviewed the data from patients treated with axi-cel at our institution. Patients had a diagnosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL), and transformed follicular lymphoma (TFL). Patients were treated with conditioning chemotherapy with cyclophosphamide and fludarabine for 3 days followed by axi-cel infusion after 2 days of rest at a dose of 2 x 106 CAR+ T cells/kg body weight. Patients were monitored for toxicities for at least 7 days in the hospital after CAR T infusion and those who had at least 30 days of follow-up after axi-cel were considered to be evaluable for safety. Cytokine release syndrome (CRS) and neurological toxicity termed as CAR-related encephalopathy syndrome (CRES) were graded according to the CARTOX grading system (Neelapu et al. Nat Rev Clin Oncol 2018). Results A total of 61 patients with relapsed or refractory large B-cell lymphoma who received axi-cel at our institution were included. Of these, 44 (72%) patients were <65 years of age and 17 (28%) patients were ³65 years of age. The baseline characteristics of the patients are summarized in Table 1. ORR and CR rates at Day 30 were comparable between the two groups. CRS was common in both groups and was observed in 83% and 91% of the patients in the older and younger age groups, respectively. But most CRS events were grade 1-2. Grade 3 or higher CRS was observed in 18% vs. 11% in the older vs. younger age groups (P=0.67). One patient with a history of autoimmune disease in the elderly group died of hemophagocytic lymphohistiocytosis (HLH). CRES was observed in 58% and 71% of the patients in the older and younger age groups, respectively. Grade 3 or higher CRES was observed in 29% vs. 39% in the older vs. younger age groups (P=0.58). Median hospitalization period for axi-cel CAR T-cell therapy was comparable between the two groups. Conclusions Our results suggest that response rates are comparable between the elderly and younger age groups at day 30 after axi-cel therapy. Importantly, toxicities due to CRS and/or CRES after axi-cel CD19 CAR T cell therapy are comparable between the elderly (³65 years) and younger (<65 years) patients with relapsed or refractory large B-cell lymphoma. Table 1 Table 1. Disclosures Nastoupil: Merck: Honoraria, Research Funding; Janssen: Research Funding; Juno: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; TG Therappeutics: Research Funding; Karus: Research Funding; Celgene: Honoraria, Research Funding; Spectrum: Honoraria; Gilead: Honoraria. Fowler:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Samaniego:ADC Therapeutics: Research Funding. Wang:Kite Pharma: Research Funding; Acerta Pharma: Honoraria, Research Funding; Novartis: Research Funding; Juno: Research Funding; Pharmacyclics: Honoraria, Research Funding; Dava Oncology: Honoraria; AstraZeneca: Consultancy, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MoreHealth: Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Westin:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Apotex: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Celgen: Membership on an entity's Board of Directors or advisory committees.

Ofatumumab Monotherapy for Treatment of Patients with Relapsed/Progressive Diffuse Large B-Cell Lymphoma: Results From a Multicenter Phase II Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3955-3955 ◽  
Author(s):  
Bertrand Coiffier ◽  
André Bosly ◽  
Ka Lung Wu ◽  
Gregor Verhoef ◽  
Van Eygen Koen ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Progression ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Large B Cell

Abstract Abstract 3955 Background: Patients (pts) with relapsed diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant (ASCT) or relapsing after ASCT have a poor prognosis and limited therapeutic options. New treatment options are needed for these pts. Ofatumumab is a human monoclonal antibody that targets a membrane-proximal epitope comprising both the large loop and small loop of CD20, and has shown effective lysis of chemotherapy-refractory DLBCL cells in vitro (Teeling et al. Blood 2004; Cillessen et al. Blood 2007; abstract 2346). We report the first results from an open-label, single-arm, international Phase II trial that evaluated ofatumumab monotherapy in relapsed or progressive DLBCL. Methods: Pts (age ≥18 years) with relapsed or progressive CD20+ DLBCL ineligible for ASCT or with relapsed or progressive disease after ASCT were enrolled between December 2007 and August 2009 (N=81). Relapsed or progressive disease was defined as relapse after a complete remission (CR) or disease progression after partial remission (PR). Pts received 8 weekly infusions of ofatumumab (dose 1, 300 mg; doses 2–8, 1000 mg). The primary endpoint was overall response rate (ORR) evaluated during the 6 months from the start of treatment, as assessed by an Independent Endpoint Review Committee according to the revised response criteria (Cheson et al. J Clin Oncol 2007). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS) and safety. Results: Baseline characteristics are shown in the Table. Pts were heavily pretreated (median 3 prior systemic therapies), and 32% of pts did not respond to their last prior therapy. Nearly all pts (96%) had received prior rituximab-containing treatment; 54% had received 2 or more courses of prior rituximab therapy (Table). Overall, 58% of pts completed all 8 infusions of ofatumumab, 65% received at least 6 infusions, and 81% received at least 4 infusions. The primary reason for treatment discontinuation was disease progression. The ORR (95% CI) was 11% (4–18%), including 3 CRs (4%) and 6 PRs (7%). Of these 9 responding pts, 8 had responded to their last systemic therapy. The median duration of response (95% CI) was 6.9 months (5.3–6.9) and median PFS (95% CI) was 2.5 months (2.3–2.9). Infusion-related events occurred in 59% of pts, primarily occurred during infusion 1 (40% of pts) and infusion 2 (22%), and subsided during subsequent infusions; these events were predominantly grade 1–2 in severity (96% of pts). The most common (>10% of pts) adverse events (AEs; any grade) were diarrhea (17%), fatigue (15%), peripheral edema (15%), neutropenia (14%), abdominal pain (12%), constipation (12%), nausea (12%), pyrexia (11%), anemia (11%) and leukopenia (11%). Of these, ≥ grade 3 events included neutropenia (10%), leukopenia (6%), anemia (5%) and fatigue (1%). Grade 3 or greater thrombocytopenia and febrile neutropenia were reported in 6% and 4% of pts, respectively. The most common infectious events were upper respiratory tract infections (7% of pts), all of which were grade 1–2 events. In total, 13 pts died during the study; 3 pts died during the treatment period and 10 pts died during post-treatment follow up (until 24 months from study start). Deaths were due to disease progression (n=10), sepsis (n=1), circulatory collapse (no further details; n=1) and multi-organ failure (n=1). Conclusions: Single-agent ofatumumab was well tolerated with an ORR of 11% in heavily pretreated pts with relapsed or progressive DLBCL, nearly all of whom had received prior rituximab therapy. Response to last systemic treatment appeared to influence response to ofatumumab in this pt population. Further studies of ofatumumab in combination with chemotherapy in relapsed DLBCL are currently underway. Disclosures: Off Label Use: Ofatumumab is an investigational anti-CD20 monoclonal antibody, currently under development for the treatment of B-cell malignancies (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, Waldenstroms macroglobulinemia and follicular lymphoma) as well as autoimmune diseases (rheumatoid arthritis and multiple sclerosis). Davies:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees. Padmanabhan:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Consultancy, Employment. Davis:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees. Losic:Genmab A/S: Employment, Equity Ownership. Lisby:Genmab A/S: Employment. Radford:GlaxoSmithKline: Equity Ownership; Genmab: Consultancy, Honoraria.

scholarly journals Ibrutinib for Transformed Lymphoma; A Report of 4 Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5115-5115
Author(s):  
Amy Sharma ◽  
Sadia Riaz ◽  
Jonathan E. Kolitz ◽  
Jacqueline C. Barrientos ◽  
Steven L Allen
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Large Cell Lymphoma ◽  
Large B Cell

Abstract Introduction Large cell lymphoma transformed from an indolent lymphoproliferative disorder typically carries a worse prognosis than de novo diffuse large B cell lymphoma. When transformation to large cell lymphoma occurs in CLL (Richter's syndrome), traditional anthracycline or platinum based therapy is associated with a median survival of <12 months. Better, more targeted therapies are needed. We describe 4 patients with transformation to large cell lymphoma who responded to ibrutinib. Cases: Patient A, age 68 at transformation, was a 64 year old male at diagnosis with CLL Rai stage 1. He was initially asymptomatic with a performance status of 0. 4 years later he developed dyspnea on exertion after one block and was found to have a left pleural effusion with diffuse lymphadenopathy with increased PET avidity. Biopsy of a supraclavicular node was positive for extracavitary primary effusion lymphoma, HHV8+, CD5-, CD10-. Patient was given R-CHOP x 6 cycles; he relapsed after 18 months and was given ibrutinib 560mg daily with monthly rituximab x 6 and achieved a PR with reversion to CLL. He is currently continuing ibrutinib in this remission for 10+ months. Patient B, age 90 at transformation, was a 68 year old female at diagnosis of CLL, Rai stage 0. She developed stage III CLL 18 years after diagnosis, was treated with BR x 6 cycles. 2 years later she developed Richter's transformation which was CD10+. Although she achieved a PR after 4 months of ibrutinib 560mg with monthly rituximab, her PS was 4 and she was transferred to hospice and expired 4.5 months after initiating ibrutinib/rituximab. Patient C, age 87 at relapse, was a 73 year old male at diagnosis when he originally presented with stage 1 DLBCL transformed from marginal zone lymphoma. He had 3 cycles of R-CHOP and RT to involved area and was disease free for 14 years until he had worsening thrombocytopenia. This was monitored for 3 years until age 87 when CT/PET showed increasing SUV in multiple lymph nodes and the spleen. Biopsy showed diffuse large B cell lymphoma, CD10-. He was started on ibrutinib 560mg with monthly rituximab x 6. He achieved a CR by CT/PET except for persistent splenic disease. He underwent splenectomy and continues in CR on ibrutinib at 9+ months. Patient D is an 83 year old female with large cell transformation from marginal zone lymphoma at diagnosis. She had stage IV disease with large cells involving pleural fluid and bone marrow. She was CD10-. She received R-CHOP x 3 with progressive disease. At that time ibrutinib 560mg alone was initiated. She has a CR based on recent CT/PET findings and is continuing ibrutinib at 18+ months. Conclusion: All of the above patients responded to ibrutinib given with or without rituximab with symptomatic and objective remissions; all of the CD10 negative cases are alive and still responding 9-18 months after initiating therapy. Studies examining the efficacy of ibrutinib in diffuse large B cell lymphoma are underway. This report supports the need for further study of ibrutinib in the transformed setting, particularly in the elderly where patients may not be appropriate for aggressive therapies. Disclosures Off Label Use: Ibrutinib was used to treat transformed large cell lymphoma.. Kolitz:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Barrientos:Gilead: Research Funding; NIH/NCATS: Research Funding; ASH-AMFDP: Research Funding. Allen:Millennium: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Equity Ownership; Onconova: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Prefmab: Final Analysis of Patient Preference for Subcutaneous Versus Intravenous Rituximab in Previously Untreated CD20+ Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3972-3972 ◽  
Author(s):  
Mathias Rummel ◽  
Tae Min Kim ◽  
Caterina Plenteda ◽  
Enrico Capochiani ◽  
Maria Mendoza ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Board Of Directors ◽  
Patient Preference ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background Rituximab in combination with chemotherapy is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). To improve patient convenience and to reduce healthcare resource burden, a subcutaneous (SC) formulation of rituximab has been developed and has been shown to be clinically comparable to intravenous (IV) rituximab. The aim of this study was to evaluate patient preference for rituximab IV or SC administration. Methods Prefmab (NCT01724021) is a randomized, open-label, crossover phase IIIb study. Eligible patients were aged ≥18 to ≤80 years with previously untreated CD20+ DLBCL (IPI 1-4 or 0 with bulky disease) or FL (FLIPI grade 1-3a), at least 1 bidimensionally measureable lesion ≥1.5cm at its largest dimension by computed tomography, and an ECOG performance status ≤3; all provided written informed consent. Patients received 8 cycles of rituximab according to 2 schedules: Arm A received 1 cycle of rituximab IV (375mg/m2) and 3 cycles of rituximab SC (1400mg) then 4 cycles of rituximab IV; Arm B received 4 cycles of rituximab IV (375mg/m2) then 4 cycles of rituximab SC (1400mg). Alongside rituximab, both arms received 6-8 cycles of chemotherapy (CHOP [cyclophosphamide, doxorubicin, oncovin, prednisone], CVP [cyclophosphamide, vincristine, prednisone], or bendamustine as per standard local practice). A Patient Preference Questionnaire (PPQ) was conducted post-rituximab therapy at cycles 6 and 8. The primary endpoint was overall preference for rituximab IV or SC. The strength of patient preference was also assessed (very strong, fairly strong, or not very strong). Adverse events (AEs), including administration-related reactions, were evaluated according to NCI-CTCAE version 4.0. Results At the primary data cut-off (January 19, 2015), the intent-to-treat population comprised 743 patients (Arm A: n=372; Arm B: n=371). The majority of patients had DLBCL (63%). The median age was 60 years (range 18-80) and baseline characteristics were balanced between arms. One hundred and twenty patients discontinued immunochemotherapy treatment prematurely, primarily due to AEs (n=52), but entered follow-up. A further 108 patients (Arm A: n=48; Arm B: n=60) discontinued the study and did not complete follow-up, primarily due to death (53 patients [DLBCL: n=48; FL: n=5], 19 of whom died due to progressive disease [DLBCL: n=16; FL: n=3]), patient request/withdrawal of consent (n=23), or AEs (n=9). Rates of study discontinuation and treatment discontinuation were balanced between arms. The PPQ was completed by 620 patients at cycle 6 and 591 at cycle 8. At cycle 6, rituximab SC was preferred by 80% (n=495) of patients (Arm A: 79%; Arm B: 81%) and rituximab IV by 10% (n=62; Arm A: 11%; Arm B: 9%), while 10% (n=63) had no preference (Arm A: 10%; Arm B: 10%). At cycle 8, the respective values were 81% (n=477; Arm A: 77%; Arm B: 84%), 11% (n=66; Arm A: 13%; Arm B: 10%), and 8% (n=48; Arm A: 10%; Arm B: 6%). The strength of patient preference for rituximab SC or IV is shown in Figure 1. Of patients who preferred rituximab SC, the main reasons were 'less time in the clinic' (cycle 6: 68%; cycle 8: 69%) and 'feels more comfortable during administration' (cycle 6: 37%; cycle 8: 37%). The mean cumulative rituximab administration time (mean ± standard deviation) was 865 ± 401 min for rituximab IV compared with 37 ± 100 min for rituximab SC. AEs were generally balanced between rituximab IV and SC administration, with the exception of gastrointestinal disorders (IV: 55%; SC: 31%) in patients with FL, notably nausea (IV: 28%; SC: 11%), constipation (IV: 14%; SC: 6%), and vomiting (IV 12%; SC 2%). No new safety signals were detected. Conclusions Most previously untreated patients with CD20+ DLBCL or FL preferred SC compared with IV administration of rituximab, mainly due to reduction in the duration and discomfort of administration. Figure 1. Figure 1. Disclosures Rummel: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Plenteda:Roche: Other: Sub-investigator. Mendoza:Roche: Employment. Smith:Roche: Employment. Osborne:Roche: Employment. Grigg:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Favorable Outcome of Primary Mediastinal Large B-Cell Lymphoma Patients Treated with Sequential R-CHOP/R- ICE Regimen Omitting Radiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3954-3954
Author(s):  
Neta Goldschmidt ◽  
Ora B. Paltiel ◽  
Dina Ben Yehuda ◽  
Geffen Kleinstern ◽  
Alexander Gural ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Clinical Laboratory ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Liver Uptake ◽  
Large B Cell Lymphoma ◽  
Number Of Patients ◽  
Large B Cell

Abstract Introduction: Progression-free (PFS) and overall survival (OS) rates for Primary mediastinal large B-cell lymphoma (PMBL) have risen to 84% and 92%, respectively, with the addition of rituximab to standard CHOP. Despite general acceptance of RCHOP as standard of care for Diffuse Large B-Cell lymphoma (DLBCL), many centers recommended alternative regimens for PMBL such as RMACOPB, RVACOPB, RCHOP-RICE and DA-EPOCH-R. The latter was adopted with great worldwide enthusiasm, despite its lack of proven superiority in randomized controlled trials (RCT). The benefits of DA-EPOCH-R include the omission of consolidation radiotherapy (RT), an attractive option in PMBL patients (pts), given their demographic profile-mainly females in their 3rd decade. We aimed to evaluate the PFS, the OS, the number of hospitalization days for treatment, and complications and the need for consolidation RT in a single center in the Rituximab era; where since 2007 over 80% of our pts were treated with the RCHOP-RICE regimen consisting of 4 courses of RCHOP followed by 3 courses of RICE. Methods: We reviewed the files of all PMBL pts who received 1st-line treatment in Hadassah Medical Center between 8/2002-10/2014, extracting clinical, laboratory and imaging data. Results: Of the 47 pts, 24 were treated with RCHOP-RICE (80% since 2007), 12 with RMACOPB, 3 with RVACOPB, 6 with RCHOP and 2 with DA-EPOCH-R. Pts were mainly female, with Stage I-II disease, and a high LDH level. Pt characteristics were comparable between the protocols (Table). In total, 21 (45%) of our pts received RT; only 3 pts (12%) treated with RCHOP-RICE compared to 18 pts (78%) treated with other protocols (p<0.01). A mean of 11+8 hospitalization days/pt were needed to administer the RCHOP-RICE regimen, significantly more than required for other treatments combined (p<0.01), except DA-EPOCH-R where the mean hospitalization days to administer 6 courses-=37+2 /pt (2 patients). Treatment-related toxicities did not differ between the groups. Late toxicity included advanced breast cancer in one pt who received RMACOPB and radiotherapy. The Deauville 5-point scale at interim was available for 39 pts, of whom 43% had an uptake </= to mediastinal blood pool, 33% had an uptake greater than the mediastinum and </= liver uptake and 23% had >liver uptake. At the end of therapy the numbers were 68%, 23% and 9% respectively, for 35 pts who were evaluated. The median 5-year PFS and OS were 93% and 98% respectively, with no difference between treatment regimens. Conclusion: The RCHOP-RICE regimen does not appear inferior to other regimens, allows to omit RT in PMBL and demonstrated no significant late toxicities. Published phase 2 data on DA-EPOCH-R (93% EFS and 95% OS) do not demonstrate an advantage compared to the simpler regimens described here. RCTs are required to establish the standard for efficacy, efficiency and safety of care in PMBL. Table 1. Characteristics RCHOP-RICE Others All patients Number of patients 24 23 47 Median age 34 34 34 Female n(%) 16 (67) 15 (65) 31 (66) Stage 1-2 n(%) 17 (71) 21 (91) 38 (81) Median tumor size (cm) 10.2 10.5 10.2 High LDH n(%) 21 (87) 17 (81) 38 (84) Effusion n(%) 10 (42) 9 (39) 19 (40) Median 5 year PFS 90% 95% 93% Median 5 year OS 100% 95% 98% Disclosures Lavie: Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Allogeneic Stem Cell Transplantation Provides Durable Remission in Patients with Primary Mediastinal Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2177-2177 ◽  
Author(s):  
Alex F. Herrera ◽  
Lu Chen ◽  
Sirin Khajavian ◽  
Matthew Lewis Chase ◽  
Justin Darrah ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Unrelated Donor ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Primary mediastinal large B-cell lymphoma (PMBCL) is a subset of aggressive B-cell non-Hodgkin lymphoma (B-NHL) with distinct biological and clinical features. Although most patients are cured with frontline chemoimmunotherapy with or without radiation therapy (RT), relapsed or refractory (rel/ref) PMBCL is much harder to control. Standard treatment of rel/ref PMBCL is similar to other aggressive B-NHLs, including salvage therapy and autologous (auto) stem cell transplantation (SCT) in chemosensitive patients. Recently, immunotherapy with PD-1 blockade and chimeric antigen receptor modified T-cells has proven to be effective in rel/ref PMBCL. Despite this, allogeneic (allo) SCT retains an important potential role as it has curative potential for patients with advanced aggressive B-NHLs. However, there are scant modern data on alloSCT outcomes in patients with PMBCL, limited to case reports or small series. We therefore performed a multicenter retrospective study to evaluate alloSCT outcomes in patients with rel/ref PMBCL. Methods: We retrospectively studied consecutive patients with rel/ref PMBCL who underwent alloSCT at Fred Hutchinson Cancer Center, Dana-Farber Cancer Institute, Massachusetts General Hospital, or City of Hope between 1/2000 and 5/2014. Baseline and transplant characteristics are reported descriptively. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Incidence of relapse and non-relapse mortality were calculated using competing risks methods. Results: 28 patients with rel/ref PMBCL underwent alloSCT at participating institutions during the study period. Among these patients, median age at SCT was 36 years, 54% were female, median number of prior therapies was 4 (range, 2-7), 57% were refractory to frontline therapy, 86% received prior RT, and 71% had prior autoSCT. At alloSCT, 1 (4%) patient was in complete response (CR), 21 (75%) were in partial response (PR), and 6 (21%) were refractory to pre-alloSCT therapy (18 patients were assessed with PET). Most patients (86%) received reduced intensity conditioning, most commonly fludarabine/melphalan +/- ATG or Zevalin (25%), fludarabine/TBI200 (21%), or fludarabine/busulfan (14%). GVHD prophylaxis most frequently consisted of a calcineurin inhibitor (CNI) with mycophenolate mofetil (12, 43%), CNI with sirolimus +/- methotrexate (8, 29%), or CNI with MTX (4, 14%). 15 (54%) patients had a matched (8/8) related donor, 8 (29%) had a matched unrelated donor, 2 had a mismatched unrelated donor (7/8), and 3 had umbilical cord donors. All patients received peripheral blood stem cell grafts except for the 3 cord recipients. The median follow-up time in survivors was 5.0 (range 0.5-14.0) years. The 2 year PFS and OS in the cohort were 39% and 45%, respectively, while non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) were 32% and 29%, respectively. The 5-year PFS, OS, NRM, and CIR were 34%, 45%, 32%, and 33%, respectively. The cumulative incidence of grade II-IV and III-IV acute GVHD were 39% and 4% at day 100, while the incidence of chronic GVHD at 1 year was 21% (18% extensive). Among patients in CR/PR at the time of alloSCT, the 2-year PFS and OS were 50% and 58%, respectively, as compared to a 2-year PFS and OS of 0% in patients who were refractory at the time of alloSCT (p=0.046 for PFS, p=0.014 for OS). One patient received post-alloSCT lenalidomide as maintenance therapy and remained in ongoing CR. Of the 9 patients who relapsed after alloSCT, 3 out of 4 patients exhibited a response to immunosuppression taper, while 4 out of 5 patients responded to subsequent systemic therapy. 2 patients underwent a donor lymphocyte infusion (DLI) and both developed subsequent GVHD - 1 patient had a CR documented 64 days after DLI while the other had continued disease progression. In the 9 patients who relapsed after alloSCT, the 2-year OS was 33%. Conclusions: AlloSCT can produce durable remissions in a subset of patients with heavily treated, rel/ref PMBCL. Patients with refractory disease at alloSCT had dismal outcomes. Despite the expanding treatment options available for these patients, alloSCT should be considered in the management of patients with rel/ref PMBCL who are sensitive to salvage therapy. Figure 1A PFS and OS After AlloSCT in Patients with Rel/Ref PMBCL Figure 1B PFS in Patients with Sensitive versus Refractory PMBCL at AlloSCT Disclosures Herrera: Merck, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; AstraZeneca: Research Funding; Gilead Sciences: Research Funding; KiTE Pharma: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Consultancy, Research Funding. Maloney:Roche/Genentech: Honoraria; GlaxoSmithKline: Research Funding; Juno Therapeutics: Research Funding; Seattle Genetics: Honoraria; Janssen Scientific Affairs: Honoraria. Ho:Jazz Pharmaceuticals: Consultancy. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Antin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding. Chen:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; REGiMMUNE: Consultancy; Magenta Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy. Armand:Otsuka: Research Funding; Affimed: Consultancy, Research Funding; Pfizer: Consultancy; Infinity: Consultancy; Merck: Consultancy, Research Funding; Adaptive: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Research Funding; Tensha: Research Funding. Shadman:Acerta Pharma: Research Funding; AbbVie: Consultancy; Genentech: Research Funding; Beigene: Research Funding; Verastem: Consultancy; Qilu Puget Sound Biotherapeutics: Consultancy; Mustang Biopharma: Research Funding; Gilead Sciences: Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Genentech: Consultancy.

scholarly journals Integrated Genetic and Topological Analysis Reveals a Hodgkin-like Mechanism of Immune Escape in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1579-1579 ◽  
Author(s):  
Gabriel K Griffin ◽  
Margaretha G.M. Roemer ◽  
Mikel Lipschitz ◽  
Jason Weirather ◽  
Christine J. Pak ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Specific Expression ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive large B cell lymphoma that typically presents with disseminated disease. In contrast to diffuse large B-cell lymphoma, not otherwise specified (DLBCL), TCRLBCL is characterized histologically by rare malignant B-cells within a robust but ineffective inflammatory background composed of numerous T cells and macrophages. TCRLBCL shows a "tolerogenic" immune signature by gene expression profiling, as well as frequent upregulation of PD-L1 (Van Loo et al. PMID: 19797726; Chen et al. PMID: 23674495). Although these features suggest that active immune evasion is central to TCRLBCL pathogenesis, its mechanistic basis is poorly understood. Accordingly, we performed an integrated analysis of tumor genetics and cell-cell interactions within the tumor microenvironment to comprehensively study PD-1:PD-L1 interactions in a multi-institutional cohort of TCRLBCL. Methods: 34 cases of TCRLBCL were identified from the pathology archives of four academic medical centers. Control cohorts containing 21 cases of DLBCL and 106 cases of classic Hodgkin Lymphoma (CHL) were used as comparators. An established fluorescence in situ hybridization (FISH) assay was used to identify copy number changes and structural rearrangements of CD274 (PD-L1) and PDCD1LG2 (PD-L2) on chromosome 9p24.1, which represents the primary genetic mechanism of PD-L1/L2 expression in CHL (Roemer et al. PMID: 27069084). Tumor-specific expression of PD-L1 and PD-L2 protein was assessed by immunohistochemistry (IHC) and scoring by two pathologists using a modified H-score (percentage of positive tumor cells [0-100%] multiplied by the mean staining intensity [0-3+]). The topology of PD-L1/PD-1 expression and cell-cell interactions in the tumor microenvironment was determined by multispectral immunofluorescence (IF) microscopy and spatial image analysis, as previously performed for CHL (Carey et al. PMID: 28893733). Results: By FISH, copy gain or amplification of PD-L1 and PD-L2 was identified in 22/34 (64.7%) cases of TCRLBCL (Figure 1A) and was associated with a 4.9-fold increase in tumor PD-L1 expression relative to cases with disomy or polysomy (mean PD-L1 H-score 72 vs 14.7, p = 0.02). A rearrangement of PD-L2 was identified in one case and associated with diffuse expression of PD-L2. These findings contrasted with those observed in the DLBCL cohort, which showed a low overall frequency of 9p24.1 copy gain/amplification (5/21 cases, 23.8%) and only minimal tumor PD-L1 expression (mean PD-L1 H-score 15.6), and were intermediate to those observed in CHL, which shows near universal copy gain/amplification of 9p24.1 (98/106 cases, 92%) and extensive tumor PD-L1 expression (mean PD-L1 H-score 143.7; Figure 1B). By multispectral IF, TCRLBCL showed prominent infiltration by PD-L1+ tumor-associated macrophages (TAM) (Figure 1C), which were 5.5-fold increased relative to DLBCL and 6.6-fold increased relative to CHL (p < 0.001). TCRLBCL also showed marked infiltration by PD-1+ T cells, which were 12.3-fold increased relative to DLBCL and 3.4-fold increased relative to CHL (p < 0.001). By spatial analysis, PD-L1+ TAMs in TCRLBCL were located in closer proximity to tumor cells than PD-L1- TAMs (p < 0.001, Figure 1D-E) and also showed frequent direct interactions with PD-1+ T cells. These findings contrasted with those in DLBCL, where no local enrichment of PD-L1+ TAMs or PD-1+ T cells was identified, and were similar but more prominent than those observed in CHL. Conclusion: TCRLBCL is characterized by recurrent gains of PD-L1 and PD-L2 on chromosome 9p24.1 in association with tumor-specific expression of PD-1 ligands, as well as prominent infiltration by PD-L1+ TAMs and PD-1+ T cells. PD-L1+ TAMs in TCRLBCL are enriched around individual tumors cells and also show frequent direct interactions with PD-1+ T cells, consistent with the establishment of an immunoevasive-niche. These findings contrast with those observed in DLBCL and are most similar to those identified in CHL. Relative to CHL, however, TCRLBCL shows less frequent gains of 9p24.1 and tumor cell expression of PD-L1, and a greater degree of infiltration by PD-L1+ TAMs and PD-1+ T cells. These findings suggest that the PD-1:PD-L1 pathway is central to immune evasion in TCRLBCL and highlight the need to test the clinical efficacy of PD-1 blockade in this patient population. Disclosures Griffin: Moderna Therapeutics: Consultancy. Freeman:Novartis: Patents & Royalties; AstraZeneca: Patents & Royalties; Dako: Patents & Royalties; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Patents & Royalties; Merck: Patents & Royalties; EMD-Serono: Patents & Royalties; Roche: Patents & Royalties; Xios: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Patents & Royalties; Bristol-Myers-Squibb: Membership on an entity's Board of Directors or advisory committees; Origimed: Membership on an entity's Board of Directors or advisory committees. Hodi:Merck: Consultancy. Shipp:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Bayer: Research Funding; AstraZeneca: Honoraria. Rodig:KITE: Research Funding; Affimed: Research Funding; Merck: Research Funding; Bristol Myers Squibb: Research Funding.

Rituximab Based Regimen May Decrease the Incidence of CNS Relapse in Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4770-4770
Author(s):  
Mervat Mahrous Mohamed ◽  
Rena Buckstein ◽  
Eugenia Piliotis ◽  
Matthew C Cheung ◽  
Neil Berinstein
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Cns Involvement ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 4770 BACKGROUND Relapse in the central nervous system (CNS) following initial treatment of diffuse large B-cell lymphoma (DLBCL) is an uncommon but fatal complication. However, the addition of rituximab improves the clinical outcome dramatically in DLBCL patients; its influence on CNS relapse is unproven. Aim This single centre retrospective study was conducted to investigate the incidence of CNS relapse, and to evaluate the impact of adding rituximab to standard CHOP (RCHOP) regimen without CNS prophylaxis in patients at risk of CNS relapse. PATIENTS AND METHODS All patients with DLBCL diagnosed from April 2002 to December 2007 at sunnybrook cancer center were retrospectively identified in the Cancer Database. Patients were included if they were >16 years old, had advanced stage (stage III /IV, or stage I /II with B symptoms, elevated LDH or bulky disease, were treated with RCHOP regimen with curative intent and were free of CNS involvement at diagnosis. CNS relapse was diagnosed by CSF cytology, radiology or clinically. Results A total of 155 patients were newly diagnosed with DLBCL and treated with RCHOP only. 22 pts were excluded, 20 had CNS prophylaxis and 2 pts had CNS involvement. 133 pts were eligible (69 male and 64 female) Median age was 64 (Age'60 was 59.4%). Stage III/IV was 69.9%. LDH was elevated in 59.4%. Bone marrow (BM) involvement and Extra nodal “>2 were 18.05% and 25.6% respectively. EN sites were: (liver 4.5%, Bone 6.8%, Pulmonary 4.5%, kidney 3.01%, cardiac 1.5%, intestine 2.3%, testicular 1.5%). The International Prognostic Index was high-intermediate/high in 55.6%. Pathologically transformed was 12.03% and were transformed from indolent histologies. BCL2 was positive in 65.4%, BCL6 was 48.9%, CD10 was positive in 49.6%, Ki-67 was >80% in 25%. All patients received RCHOP (Median 6 cycles, (range 2-8). Overall response (ORR) was 88.6%, CR/CRU 72.7% with a median follow up 24.6 months (range 2.6-75.5). 28 patients (21.05%) relapsed systemically. Two patients (1.5%) had a CNS relapse 1 brain parenchyma and 1 leptomeningeal one month after systemic relapse. The median time to CNS relapse was 10.4 mos (6.24-14.5 mos). In univariate risk factor analysis (LDH (p=0.8), IPI>3 (p=0.9), No of EN (p=0.9). Actuarial 5 y Overall Survival (OS) was 67.3% (95% CI (57-77%) and progression free Survival (PFS) was 65.7% (95% CI (52.3-78.6%). Conclusion Our data suggest that the addition of rituximab may reduce the risk of CNS relapse for poor risk patients likely through systemic control. Future prospective studies of rituximab-containing chemotherapies with CNS prophylaxis are warranted Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Diving Bell and the Butterfly Revisited: A Fatal Case of Locked-in Syndrome in a Man With Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

2018 ◽  
Vol 11 ◽  
pp. 1179545X1876279
Author(s):  
Jacqueline N Poston ◽  
Russell Dorer ◽  
David M Aboulafia
Keyword(s):  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Epstein Barr ◽  
Large B Cell

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare variant of DLBCL. The natural history of this subtype is poorly understood. Incomplete literature in the era of rituximab suggests that patients with EBV-positive DLBCL have similar outcomes to patients with EBV-negative DLBCL when treated with rituximab and anthracycline-based chemotherapy regimens; however, there are few prospective studies on this subtype and little is known about the risk of central nervous system (CNS) relapse with EBV-positive DLBCL. Herein, we describe the case of a 64-year-old man who presented with stage IIA EBV-positive DLBCL. His international age-adjusted International Prognostic Index (IPI) was 2. He achieved a complete response to 6 cycles of rituximab combined with chemotherapy consisting of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. After 10 days of completion of chemotherapy, he had a fulminant neurologic decline manifested by diffuse weakness followed by a locked-in syndrome; he could only communicate by moving his eyes. He had been deemed at low risk for CNS relapse based on the application of the recently developed CNS-IPI score of 2 (1 point for age >60 years and 1 point for lactate dehydrogenase higher than normal) and consequently did not receive therapy for CNS prophylaxis. A limited postmortem autopsy revealed extensive lymphoma throughout the brain, particularly in the deep basal nuclei, midbrain, pons, centrum semiovale, and corpus callosum. This presentation of CNS relapse is rare and has not yet been described in EBV-positive DLBCL. We discuss some of the unique aspects of this case including the clinical manifestations of locked-in syndrome and its differential diagnosis and the uncertain benefits of CNS prophylaxis in this clinical context.

scholarly journals Describing Treatment of Primary Mediastinal Large B Cell Lymphoma Using Rigorously Defined Molecular Classification: A Retrospective Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Carla Casulo ◽  
Myla Strawderman ◽  
Raphael Steiner ◽  
Carolyne Delage ◽  
Tina Faugh ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Molecular Features ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Introduction Primary mediastinal large B cell lymphoma (PMBCL) is a rare non-Hodgkin lymphoma (NHL) with a female predominance; often presenting with a large anterior mediastinal mass. Though PMBCL has clinical and molecular features overlapping with Hodgkin lymphoma, it is a distinct entity defined by the World Health Organization classification. PMBCL is heterogeneously treated, and most patients receive front line therapy with either rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with radiotherapy (RT), or the more intensive etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with rituximab (EPOCH-R) regimen. Diagnosis of PMBCL is made using clinicopathologic criteria and radiographic imaging, however gene expression profiling (GEP) studies reveal a characteristic genotypic signature distinct from diffuse large B cell lymphoma (DLBCL). Molecular classification of PMBCL using the Lymph3Cx assay from formalin-fixed paraffin-embedded tissue (FFPE) is feasible, reproducible, and highly concordant in a training and validation cohort (Mottok et al. Blood 2018). Using a multicenter cohort of patients, we sought to estimate the rate of mis-match among patients with a clinical diagnosis of PMBCL using Lymph3Cx, and describe treatment selections and outcomes for each group. Methods Patients were identified from a cohort of patients with newly diagnosed NHL from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource, and the Lymphoma Epidemiology of Outcomes cohort. Patients were enrolled between 2002-2019, and included if they had clinically defined PMBCL. FFPE was retrieved from hematopathology archives of participating academic centers. All diagnoses of PMBCL were based on expert hematopathology review at the time of therapy, and all cases underwent classification by GEP using the Lymph3Cx assay. Lymph3Cx was performed in the clinical lab at the Mayo Clinic in Arizona: Contiguous unstained sections were deparaffinized and macrodissected to enrich for tumor content before RNA isolation;100-200 ng of total RNA was used in an nCounter Elements XT, hybridized, and processed the following day using the nCounter FLEX system. Raw counts were processed through the Lymph3Cx algorithm and results reported as probability of PMBCL (≥0.90 as PMBCL, ≤0.10 as DLBCL all other results "Unclear PMBCL/DLBCL") (A. Mottok et al, Blood, 2018). For cases classified as DLBCL, the Lymph2Cx cell-of-origin classifier results was reported (Scott et al, JCO, 2016). Time to event endpoints were described with Kaplan-Meier plots by groups defined by mismatch status and compared with a logrank test. Binary outcomes will be presented with 90% exact confidence intervals. Results Fifty patients were identified. Median age was 35 years (range 19-70). Sixty four percent were women. Median follow up was 47 months. Treatments included R-CHOP (44%), EPOCH-R (44%), and MACOP-B [methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin] (6%), other (4%). Ten patients (20%) had events (defined as progression or death). Three patients in the entire cohort (6%) died. The Kaplan-Meier estimated survival at 47 months (median follow-up) is 92%. The Lymph3Cx assay yielded gene expression data of sufficient quality in 47/50 cases (94%, 90% CI=85.2, 98.3%). Of 47 cases clinically identified as PMBCL, 5 unclear were DLBCL/PMBCL and 1 was Germinal Center B cell subtype of DLBCL. Among these 6 patients, 4 received R-EPOCH (66%), 1 received R-CHOP (16.6%). One patient had missing treatment data. One patient had an event requiring subsequent therapy; all patients remain alive. Conclusions Using 47 patients with PMBCL defined by histology, clinical and radiographic findings, and molecular features, we demonstrate high concordance between clinical phenotype and molecular genotype of PMBCL by Lymph3Cx. Among the 6 patients not classified as PMBCL, most received R-EPOCH. Differences in outcome by mis-match status await longer follow-up and further accrual of subjects to our data base. Our data suggest molecular genotyping may have a role in mediastinal presentations of large cell lymphoma to optimize treatment decision making. Disclosures Maurer: Nanostring: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding. Flowers:AbbVie: Consultancy, Research Funding; Kite: Research Funding; Burroughs Wellcome Fund: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; V Foundation: Research Funding; Bayer: Consultancy; National Cancer Institute: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Astellas: Consultancy; Bayer: Consultancy; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy; Roche: Other: Travel expenses; Seattle Genetics: Research Funding.

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