bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of PD-L1 inhibitor durvalumab with R-CHOP or R2-CHOP in subjects with previously untreated, high-risk DLBCL.
Authors: Nowakowski Grzegorz S. , Willenbacher Wolfgang , Greil Richard , Larsen Thomas Stauffer , Patel Krish , Jäger Ulrich , Manges Robert F. , Trumper Lorenz H. , Haioun Corinne , Everaus Hele , Kalakonda Nagesh , Knoble Jeanna , Brown Peter , Joergensen Judit Meszaros , Cunningham David , Domper Neus , Casadebaig Marie-Laure , Manzke Oliver , Munoz Javier 
Published: March 2020

7520 Background: We report results of a phase 2, open-label study of durvalumab (durva) in combination with R-CHOP or R2-CHOP (R-CHOP + lenalidomide) in previously untreated, high-risk diffuse large B-cell lymphoma (DLBCL). Methods: Subjects (≥18 y; ECOG 0–2) with previously untreated, high/high-intermediate risk DLBCL (IPI ≥3/NCCN-IPI ≥4) were stratified to durva + R-CHOP (Arm A, GCB DLBCL) or R2-CHOP for 6–8 cycles (Arm B, ABC DLBCL) based on cell of origin identified by gene expression followed by durva consolidation up to month 12 from start of induction. After FDA placed clinical holds on trials including combination therapy with checkpoint inhibitors and immunomodulatory agents, the study was revised to include both ABC and GCB in Arm A (durva + R-CHOP). The primary endpoint was complete response rate (CRR) at end of induction; secondary endpoints were rate of subjects continuing to consolidation, safety, and response in biological. Results: A total of 46 subjects were treated (safety; A/B, n=43/3); median age, 62/66 y; male, 61%/67%; ECOG 2, 19%/33%; Ann Arbor stage IV, 79%/33%; bulky disease: 49%/67%; double/triple-hit lymphoma, 30%/33%. As of Aug 2, 2018, 30/3 (A/B) had completed induction therapy, and 19 subjects (A) were ongoing. CRR (95% confidence interval) at end of induction was (A) 54% (37%-71%) and (B) 67% (9%-99%); 68%/67% (A/B) continued to consolidation therapy and were progression free at month 12. Safety profile was as expected for the components of the combination regimen with no new safety signal identified. Frequent treatment-emergent adverse events (TEAEs; ≥25%; A+B) included fatigue (61%), neutropenia (52%), peripheral sensory neuropathy (50%), nausea (46%), diarrhea (28%); constipation, decreased appetite, insomnia, pyrexia (24% each); and alopecia, dizziness, dyspnea, headache, stomatitis (22% each). Grade 3/4 TEAEs occurred in 84%/100% of subjects (A/B), and 3 subjects (2/1) died with no death related to study treatment. Follow-up for efficacy and safety is ongoing. Conclusions: Durva + R-CHOP combination therapy is safe and demonstrates encouraging response rates in subjects with high-risk DLBCL including double-hit lymphoma. Clinical trial information: NCT03003520.
Update of the single-arm phase II L-MIND study of MOR208 + lenalidomide (LEN) in relapsed/refractory diffuse large B-cell lymphoma (R-R DLBCL): Response rates in patient subgroups with poor prognosis.
Authors: Maddocks Kami J. , Duell Johannes , González Barca Eva , Jurczak Wojciech , Liberati Anna Marina , Nagy Zsolt , Obr Aleš , Gaidano Gianluca , André Marc , Kalakonda Nagesh , Dreyling Martin H. , Zinzani Pier Luigi , Dirnberger-Hertweck Maren , Weirather Johannes , Ambarkhane Sumeet Vijay , Salles Gilles A. 
Published: March 2020

7521 Background: MOR208, an Fc-enhanced, humanized, anti-CD19 monoclonal antibody has shown single agent activity in patients (pts) with R-R DLBCL and encouraging activity when combined with LEN in the phase II L-MIND study. Here we report an update with primary endpoint and subgroup analyses (cut off June 5, 2018). Methods: Key inclusion criteria were adequate organ function, ≤3 prior lines of therapy, including ≥1 anti-CD20 therapy, and ineligibility for stem cell transplantation. Treatment comprised up to 12, 28-day (d) cycles (C) of MOR208, 12 mg/kg IV, q1w C1–3 (loading dose on d4 of C1), and q2w C4–12 + LEN 25 mg PO d1–21, C1–12. Pts progression-free after 12 C received MOR208 q2w until progression. The primary endpoint was independent review committee (IRC)-assessed ORR as per Cheson 2007 criteria. Results: Recruitment is complete (N = 81): median age 72 years (range 41–87), median of 2 prior therapies, 19 (23%) of pts had early relapse (≤12 months [mo] from diagnosis), 32 (40%) were rituximab (RTX) refractory (no response to or progression during or within 6 mo of a prior RTX therapy), 34 (42%) were refractory to their last therapy, 21/40 (26%/49%) pts had non-germinal center B cell-like (GCB)- / GCB-DLBCL, and 42 (52%) had an International Prognostic Index (IPI) of 3–5. MOR208 + LEN therapy was well tolerated; 72% of pts stayed on a LEN dose of ≥20 mg/day. Treatment-related serious adverse events, mainly infections (10%) or neutropenic fever (5%), occurred in 17% of pts. Investigator (INV)-assessed complete response (CR) and partial response rates were 33% and 25%, respectively, giving an ORR of 58%, comparable to the IRC assessment (ORR 54%; CR 32%). ORR was 46% in pts with ≥2 prior therapies, 59%/56% in rituximab- / last treatment-refractory pts, 58% in early relapse pts, 57% in pts with a baseline IPI of 3–5, and 71% in pts with non-GCB- vs 53% with GCB-DLBCL. INV-assessed median PFS and OS (ITT analysis) were 16.2 mo (95% CI: 6.3–NR) and not reached (95% CI: 18.6–NR), respectively. Conclusions: MOR208 + LEN shows encouraging activity including a durable PFS in R-R DLBCL, and in pt subgroups with poor prognosis. Clinical trial information: NCT02399085.
Long-term follow-up of previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) treated with ofatumumab (OFA) and chlorambucil (CHL): Final analysis of the phase 3 COMPLEMENT 1 trial.
Authors: Offner Fritz , Robak Tadeusz , Janssens Ann , Kanakasetty Govind Babu , Kloczko Janusz , Grosicki Sebastian , Mayer Jiri , Panagiotidis Panagiotis , Schuh Anna , Pettitt Andrew , Montillo Marco , Werner Olena , Vincent Ghislaine , Khanna Sadhvi , Hillmen Peter 
Published: March 2020

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.
Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Extended follow-up on the multicenter, single-arm phase II ORIENT-1 study.
Authors: Su Hang , Song Yongping , Jiang Wenqi , Sun Xiuhua , Qian Wenbin , Zhang Wei , Gao Yuhuan , Jin Zhengming , Zhou Jianfeng , Jin Chuan , Zou Liqun , Qiu Lugui , Li Wei , Yang Jianmin , Hou Ming , Zeng Shan , Liu Peng , Shi Yuankai , Zhou Hui , Wang Shuyan 
Published: March 2020

7533 Background: Classical Hodgkin’s lymphoma (cHL) is characterized by chromosome 9p24.1 alterations and PD-1 ligand overexpression. Sintilimab, a programmed death-1 checkpoint inhibitor, has demonstrated efficacy in relapsed/refractory cHL after the primary analysis of the ORIENT-1 study. Here, we report the updated safety and efficacy prolines after extended follow-up. Methods: ORIENT-1 is a multicenter, single-arm, phase II study in China. Classical Hodgkin’s lymphoma patients who had failed ≥2 lines of systemic therapy, including autologous hematopoietic stem cell transplantation (HSCT) were enrolled. Sintilimab, 200 mg IV was given every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response rate (ORR) assessed by an independent radiological review committee (IRRC) according to 2007 IWG criteria. Results: 96 patients were treated. As of the data cutoff on 16 October, 2018 72.9% of patients were continuing treatment with a median follow-up of 14 months. Median number of treatment cycles was 20 (range: 1 to 26). ORR was 85.4% (82/96, 95%CI: 76.7 to 91.8) based on IRRC review. Twenty-eight patients (29.2%) achieved complete response (CR) by PET scan. At the time of analysis, 59 out of 82 patients who had achieved complete or partial response continued to have an on-going response. The median duration of response (DoR) and progression free survival (PFS) have not been reached. The most common treatment-related adverse event (TRAE) was pyrexia (40.6%, 39/96), 92.3% of which was grade 1 or 2. The most common grade 3 or 4 TRAEs were pyrexia (3.1%) and anemia (3.1%). One death occurred which was not considered treatment related. Conclusions: ORIENT-1 study has the largest cohort of cHL patients in China treated with a PD-1. In addition to a high rate of response, sintilimab also demonstrated durable efficacy and favorable long-term safety profile after extended follow-up. Clinical trial information: NCT03114683.
Time to next treatment in patients with previously treated cutaneous T-cell lymphoma (CTCL) receiving mogamulizumab or vorinostat: A MAVORIC post-hoc analysis.
Authors: Pro Barbara , Kim Youn H. , Ortiz-Romero Pablo L. , Sokol Lubomir , Scarisbrick Julia , Musiek Amy , Vermeer Maarten , Dummer Reinhard , Halwani Ahmad Sami , Fierro Maria Teresa , Moriya Junji , Leoni Mollie , Bagot Martine 
Published: March 2020

7539 Background: CTCLs are chronic skin malignancies, characterized by relapsing/remitting behavior and progressive resistance to treatments, with a reported median time to next treatment (TTNT; ie, systemic treatment excluding topical steroids) in mycosis fungoides (MF) and Sezary syndrome (SS) of 5.4 months (mo) (Hughes et al. Blood, 2015). The phase 3 MAVORIC study demonstrated mogamulizumab (MOGA) was superior to vorinostat (VORI) in progression-free survival (median 7.7 vs 3.1 mo, P<0.0001) and confirmed overall response rates (28% vs 4.8%, P<0.0001) in previously treated patients with MF/SS (Kim et al. Lancet Oncol 2018). This post-hoc analysis examines TTNT to further explore the patient clinical experience. Methods: Patients with MF/SS who were treated with ≥1 prior systemic therapy were randomized 1:1 to receive MOGA (1.0 mg/kg, administered once weekly for the first 28-day cycle, then on Days 1 and 15 of subsequent cycles) or oral VORI (400 mg daily). Patients on VORI were permitted to crossover to MOGA upon approval. TTNT was defined as time to any therapy excluding topical steroids or focal radiation. The length of TTNT was assessed overall and by disease stage grouping (IB/II and III/IV) and disease type (MF and SS). Results: Median TTNT for the full ITT population was longer with MOGA at 11 mo (95% CI, 8.8-12.6) compared to VORI at 3.5 mo and consistently longer for MOGA vs VORI across disease stage grouping or by disease type (Table). Conclusions: TTNT in MF/SS represents an additional measure of clinical benefit and disease control in patients who may have progressed based on strict protocol definitions of progression. This post hoc analysis showing a prolonged TTNT across disease stages and types supports a clinical benefit for MF and SS patients who receive MOGA. Clinical trial information: NCT01728805. [Table: see text]
Prognostic value of baseline SUVmax in patients with advanced stage follicular lymphoma receiving frontline rituximab-based therapy.
Authors: Strati Paolo , Ahmed Mohamed Amin , Fowler Nathan Hale , Hagemeister Fredrick B. , Fayad Luis , Rodriguez Maria Alma , Samaniego Felipe , Wang Michael , Westin Jason , Romaguera Jorge Enrique , Noorani Mansoor , Phansalkar Karishma , Cheah Chan , Feng Lei , Davis Richard Eric , Nastoupil Loretta J. , Neelapu Sattva Swarup 
Published: March 2020

7540 Background: Positron emission tomography (PET) is recommended in follicular lymphoma (FL) for initial staging, evaluation of potential transformation, and response assessment. The prognostic value of pre-treatment PET scan has not been adequately explored. Methods: We performed a single-institution retrospective analysis of patients with advanced stage FL, without histological evidence of transformation, treated with frontline rituximab-based therapy, and analyzed the prognostic significance of baseline maximum standardized uptake value (SUVmax). Results: The median follow-up for the cohort was 94 months. Of 346 patients, 151 (44%) received R-CHOP and 195 (56%) received non-R-CHOP regimens. Among multiple single unit increments of SUVmax, a value of >18 showed the strongest association with progression-free survival (PFS) (hazard ratio [HR] 1.5, 95% confidence interval (CI) 0.95-2.3, p=0.08), and was selected as cut-off for further analysis. Fifty-two (15%) patients had a SUVmax > 18. On univariate analysis, factors associated with SUVmax > 18 were male sex (67% vs 52%, p=0.05), elevated β2-microglobulin (65% vs 47%, p=0.02), elevated LDH (37% vs 13%, p<0.001), presence of B symptoms (35% vs 14%, p=0.01), and largest lymph node ≥ 6 cm (64% vs 30%, p<0.001). On multivariate analysis, largest lymph node ≥ 6 cm was the only factor maintaining its association with SUVmax > 18 (odds ratio [OR] 2.7, 95% CI 1.3-5.3, p=0.006). SUVmax > 18 significantly associated with a lower CR rate among patients treated with non-R-CHOP regimens (45% vs 92%) (p<0.001) but not among patients treated with R-CHOP (p=1). SUVmax > 18 associated with significantly shorter PFS among patients treated with non-R-CHOP regimens (77 months vs not reached, p=0.02), but not among patients treated with R-CHOP (p=0.73). SUVmax > 18 associated with shorter overall survival (OS) both in patients treated with R-CHOP (15 year OS 70% vs 75%, p=0.02) and non-R-CHOP regimens (15 year OS 50% vs 75%, p=0.001). Conclusions: In conclusion, baseline SUVmax has prognostic value in patients with advanced stage FL receiving rituximab-based therapies. Evaluation in prospective studies is needed to further confirm these findings.
Survival disparities of diffuse large B-cell lymphoma in a community-based cancer center.
Authors: Jorge Vinicius Machado , Tiu Andrew Chua , Moussa Peter , Gupta Sorab , Djibo Djeneba Audrey , Dourado Claudia M. 
Published: March 2020

7541 Background: Non-Hodgkin’s Lymphoma (NHL) is a heterogeneous group of hematologic malignancy from immature or mature lymphocytes or natural killer cells. It is the 9th leading cause of death for both sexes. Diffuse Large B Cell Lymphoma (DLBCL), a subset of NHL, comprises 30 – 40% of all NHL. The etiology for the racial disparities in survival among patients with DLBCL is still unknown. The Revised International Prognostic Index (R-IPI), a tool which predicts the outcome of DLBCL patients, has not yet been fully validated in African Americans (AA). Methods: We conducted a single cohort study of patients diagnosed with DLBCL from January 1, 2007 to December 31, 2017 from our tumor registry in a single community-based cancer center. We abstracted demographic, clinical, histopathologic, treatment, and R-IPI variables. Our primary endpoint was overall survival (OS). Our secondary endpoints were factors that determine mortality through Cox multivariate analysis. Results: Among 381 patients with NHL, 181 (47.5%) patients had biopsy-proven DLBCL. Median age was 65 years old, 47% were males, 41% were AA, 44% were Caucasians, 46% were stage IV by Ann-Arbor staging. African-Americans (AA) had a median OS of 15.7 months (95% CI, 10.31 to 23.90) compared to non-AA 93.6 months (95% CI, 61.48 to 142.57). Even after adjusting for race, R-IPI was correlated with mortality on all patients. Lactate dehydrogenase levels were significantly higher in AA (P<0.001) but there was no difference in the interval from diagnosis to initiation of treatment in all groups. The presence of B symptoms HR 1.80 (95% CI, 1.17 to 2.77), African-American race HR 2.19 (95% CI, 1.38 to 3.52), positive HIV HR 2.16 (95% CI, 1.15 to 4.05), chronic liver disease HR 1.87 (95% CI, 1.09 to 3.23), and malnutrition HR 2.46 (95% CI, 1.30 to 4.65) were all independently associated with increased mortality. Histopathologic features such as the cell of origin, BCL6, and BCL2 rearrangements were not independently associated with increased mortality. Conclusions: There is an overwhelming disparity in survival among AA with DLBCL. The R-IPI is a reliable tool for predicting mortality in AA with DLBCL.
Outcomes of lenalidomide in diffuse large B-cell (DLBCL) and high-grade NHL (HGBCL): A single-center retrospective analysis.
Authors: Rodgers Thomas David , Baran Andrea M , Reagan Patrick Michael , Casulo Carla , Evans Andrew , Burack Walter Richard , Friedberg Jonathan W. , Barr Paul M. 
Published: March 2020

7547 Background: Outcomes remain poor for patients with relapsed refractory DLBCL and HGBCL, especially those ineligible for a stem cell transplant or CAR T-cell therapy. Lenalidomide has efficacy in these groups, most notably in the activated B-cell like (ABC) subtype when defined by gene expression profiling. We analyzed the outcomes of consecutive patients with DLBCL treated with lenalidomide, focusing on characteristics such as transformed histology and MYC translocation status. Methods: We performed a retrospective review of consecutive patients with transformed indolent NHL, DLBCL, and HGBCL treated with lenalidomide at the University of Rochester between 2011-2018. Cell of origin was determined by Hans algorithm and FISH was performed to detect MYC, BCL2, and BCL6 translocations. Kaplan Meier estimates and descriptive statistics were utilized for analysis. Results: 62 patients were identified with a median age of 76 years, the majority with > 2 prior therapies. ORR was 43.5%, including 14 patients with a CR. Median PFS was 4.6 months with 18 patients achieving a PFS > 1 year. Median OS was 14 months. No difference in PFS, OS, or ORR was observed between the de novo germinal center b-cell (GCB) and non-GCB populations (PFS 4 vs. 5 months, p = 0.87). 16 patients with transformed FL had a median PFS of 24 months and a median OS of 46.7 months (vs. de novo GCB OS of 7.8 months, p = 0.02). Notably, 6/7 MYC+ patients achieved an objective response, including 3 with a CR. All patients with double and triple hit disease had an objective response, including two PRs and one CR. Conclusions: Our experience confirms the clinical activity of lenalidomide in heavily pretreated older adults with DLBCL. Outcomes did not differ by cell of origin using the Hans immunohistochemistry algorithm and durable responses were observed, particularly in transformed FL. Nearly all of the MYC+ patients responded, including those with double/triple hit genetics, and almost half achieved a CR. Based on our data, lenalidomide may be an optimal bridge to consolidative cellular therapy in high-risk patients irrespective of genotype, particularly in transformed indolent histologies.
Extranodal (EN) and spleen disease by FDG-PET/CT is associated with early clinical failure in untreated follicular lymphoma (FL).
Authors: St-Pierre Frederique , Broski Stephen M , LaPlant Betsy , Ristow Kay , Maurer Matthew John , Macon William R , Habermann Thomas Matthew , Ansell Stephen M. , Thompson Carrie A. , Micallef Ivana N. M. , Nowakowski Grzegorz S. , Witzig Thomas E. 
Published: March 2020

7554 Background: Predicting early clinical failure in patients with untreated FL is important but difficult. Lymphoma involvement of EN sites is better detected by FDG-PET/CT than CT alone, but PET parameters are not part of the usual predictive indices. We aimed to determine the incidence and patterns of spleen and EN disease using PET/CT, and learn if they are useful in predicting early clinical failure. Methods: PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed. The location, pattern, and number of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event-free survival (EFS) and overall survival (OS). Results: 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone, or soft tissue involvement, as well as a multifocal on diffuse pattern of bone involvement by imaging, were univariate predictors of EFS; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table). When the multivariate analysis was performed using PRIMA-PI factors, the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01-5.18; p=0.05). Conclusions: Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure of FL. These results may be useful to better identify high-risk patients and guide appropriate therapy. [Table: see text]