bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of characteristics, survival trends, and associated malignancies of B-cell and T-cell prolymphocytic leukemia: A surveillance, epidemiology, and end results (SEER) based study1998 to 2016.
Authors: Attia Doaa , Attia Sara Aly 
Published: May 2020

7558 Background: Prolymphocytic leukemia (PLL) compromises two subsets; B-cell and T-cell, accounting for less than 2% of mature lymphocytic leukemia. Both of them are rare lymphoid neoplasms with a very aggressive clinical course and poor prognosis. Methods: We used SEER program dataset between 1998 and 2016. We divided the patients into 2 groups: B-PLL and T-PLL and identified them using ‘ICD-O-3 histology recode: 9833/3 and 9834/3 respectively. We used SPSS software (version 26, IBM, NY, USA) to calculate overall survival using Kaplan-Meier methods and compare the survival between the two subtypes using the log-rank test. We also used multivariable covariate-adjust cox models to determine the impact of age, sex, race, cause of death, and associated primary malignancies on survival in both types. Results: A retrospective cohort study of 783 patients (295 B-PLL and 488 T-PLL) with overall survival rate of 22.5% (30.2% B-PLL and 18% T-PLL). The overall median survival for PLL was 16 months (95 CI, 13.745-18.255). The median survival of B-PLL (25 months, 95%CI, 15.733-34.267) was much better than T-PLL (14 months, 95%CI, 11.922-16.078). The mean age was 68.7±15.3. Patient age was an independent factor in determining the survival and inversely associated with survival time in both types (p < 0.0001). The survival rate was worst ) among age groups older than 79, between 70-79 years (8.9%, 18.9%) respectively. Although white male patients were more affected in both types, neither sex nor race significantly affected survival (P 0.554, 0.062 respectively). 64.7% of PLL patients died due to cancer. Patients with cancer-related death had significantly shorter survival time in both T-PLL group (HR = 0.351, 95% CI 0.241-0.512) and B-PLL group (HR = 0.682, 95% CI 0.491-0.945). We also found that 24.4% of B-PLL and 19% of T-PLL patients have another associated primary malignancy. Among hematological malignancies, non-hodgkin lymphoma was the commonest. Although associated solid tumors were less common, Prostate cancer and breast cancer were the commonest for both types and lung/bronchus malignancies were more associated with T-PLL. Conclusions: T-PLL subtype has worse prognosis. Age is the most important independent predictor of survival in both types. Although most of affected patients were white males, race and gender have no impact on survival. Non-hodgkin lymphoma is the commonest primary associated malignancy followed by breast and prostate cancer in both types.
Interim analysis of ZUMA-5: A phase II study of axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory indolent non-Hodgkin lymphoma (R/R iNHL).
Authors: Jacobson Caron A. , Chavez Julio C. , Sehgal Alison R. , William Basem M. , Munoz Javier , Salles Gilles A. , Casulo Carla , Munshi Pashna N. , Maloney David G. , De Vos Sven , Reshef Ran , Leslie Lori A. , Yakoub-Agha Ibrahim , Oluwole Olalekan O. , Fung Henry C. , Plaks Vicki , Yang Yin , Lee Jennifer , Avanzi Mauro P. , Neelapu Sattva Swarup 
Published: May 2020

8008 Background: Advanced stage iNHL, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), is considered incurable as most pts experience multiple relapses (Wang, et al. Ther Adv Hematol. 2017), highlighting a need for novel therapies. Here, we present interim results from ZUMA-5, a Phase 2, multicenter study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in pts with R/R iNHL. Methods: Adults with R/R FL (Grades 1-3a) or MZL (nodal or extranodal) after ≥ 2 lines of therapy (including an anti-CD20 monoclonal antibody [mAb] with an alkylating agent), and an ECOG of 0 – 1 were eligible. Pts were leukapheresed and received conditioning chemotherapy followed by axi-cel infusion at 2 × 106 CAR T cells/kg. The primary endpoint was objective response rate (ORR) by central review (Cheson, et al. J Clin Oncol. 2014). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T cells. Results: As of 8/20/19, 94 pts (80 FL; 14 MZL) received axi-cel with a median follow-up of 11.5 mo (range, 4.2 – 24.9). Median age was 63 y (range, 34 – 79), 47% of pts were male, 52% had stage IV disease, 51% had ≥ 3 FLIPI, and 59% had high tumor bulk (GELF). Pts had a median 3 prior lines of therapy, 66% progressed < 2 y after initial anti-CD20 mAb-containing therapy (POD24), and 73% were refractory to the last prior treatment. Of 87 pts evaluable for efficacy, ORR was 94% (79% complete response [CR] rate). Pts with FL (n = 80) had an ORR of 95% (80% CR rate). Pts with MZL (n = 7) had an ORR of 86% (71% CR rate). Overall, 68% of pts had ongoing responses as of the data cutoff. Updated data, including DOR, PFS, and OS with longer follow-up, will be included in the presentation. Of 94 pts evaluable for safety, 83% experienced Grade ≥ 3 adverse events (AEs), most commonly neutropenia (33%) and anemia (28%). Grade ≥ 3 cytokine release syndrome (CRS; per Lee et al, Blood 2014) and neurologic events (NEs; per CTCAE v4.03) occurred in 11% and 19% of pts, respectively. Median times to onset of CRS and NEs were 4 and 7 d, with median durations of 6 and 14.5 d. There were 2 Grade 5 AEs: multisystem organ failure in the context of CRS (related to axi-cel) and aortic dissection (unrelated to axi-cel). Median peak and AUC0-28 CAR T cell levels were 44 cells/µL and 490 cells/µL × d, respectively. Conclusions: Axi-cel demonstrated significant and durable clinical benefit, with high rates of ORR and CR, and a manageable safety profile in pts with R/R iNHL. Clinical trial information: NCT03105336 .
Effect of adding ublituximab to ibrutinib on PFS, ORR, and MRD negativity in previously treated high-risk chronic lymphocytic leukemia: Final results of the GENUINE phase III study.
Authors: Sharman Jeff P. , Brander Danielle M. , Mato Anthony R. , Ghosh Nilanjan , Schuster Stephen J. , Kambhampati Suman , Burke John M. , Lansigan Frederick , Schreeder Marshall T. , Lunin Scott D , Zweibach Alexander , Shtivelband Mikhail , Travis Patrick M. , Chandler Jason Claud , Kolibaba Kathryn S. , Sportelli Peter , Miskin Hari P. , Weiss Michael S. , Flinn Ian 
Published: May 2020

8022 Background: The BTK inhibitor ibrutinib (IB) has advanced the treatment for patients (pts) with CLL, however, among pts with high-risk CLL, disease control with IB is less durable. Ublituximab (UTX) is a glycoengineered mAb with enhanced ADCC. The GENUINE study evaluated the addition of UTX to IB vs. IB alone in high-risk rel/ref CLL. With a median follow up now 3.5+ yrs, we present the final results. Methods: Eligible pts having rel/ref CLL with centrally confirmed del17p, del11q, and/or a TP53 mutation, were randomized 1:1 to IB (420 mg QD) alone or with UTX (900 mg on D1, 8, 15 of Cy 1, D1 of Cy 2-6, and Q3 Cy thereafter). No limit on # of prior Tx; prior IB excluded. Primary endpoint was overall response rate (ORR) by iwCLL 2008 (excludes PR-L); secondary endpoints were CR rate, peripheral blood MRD negativity (analyzed centrally), PFS, and safety. Response was by blinded independent review. Results: 117 pts were treated (59 in UTX + IB arm; 58 in IB arm). Med age was 66 yrs and med # of prior Tx was 1 (range 1-5) for each arm. Baseline features were relatively balanced including ECOG, gender, and med time since diagnosis (6+ yrs). 17p del was greater in the IB arm (50% vs 44%); bulky disease was greater in UTX + IB arm (47% vs 28%); IGHV-unmut was 83% for both arms. At data-cutoff of Sep 1, 2019, AEs were comparable between the arms, except infusion reactions (UTX + IB: All G 53% / G 3/4 3%) and neutropenia (All G 36% vs 21%, G 3/4 19% vs. 12%) which were higher for UTX + IB. At a med follow up of 42 mos, all efficacy endpoints were in favor of UTX + IB (see Table). Conclusions: In contrast to prior studies adding rituximab to IB, GENUINE is the first randomized trial to demonstrate a PFS benefit with the addition of an anti-CD20 to IB. Increasing depth of response (CR rate, MRD-neg) post first year of Tx supports maintenance therapy with UTX. Clinical trial information: NCT02301156 . [Table: see text]
Gls-010, a novel anti-PD-1 mAb in Chinese patients with relapsed or refractory classical Hodgkin lymphoma: Preliminary impressive result of a phase II clinical trial.
Authors: Song Yuqin , Zhu Jun , Lin Ningjing , Zhang Mingzhi , Bai Hai , Liu Hui , Cui Jie , Ke Xiaoyan , Zhang Huilai , Liu Lihong , Yan Dongmei , Jiang Yongsheng , Zang Aimin , Qi Junyuan , Wang Li , Liu Zhuogang , Xu Bing , Zhang Ying , Zhang Zhihui , Meng Haijin 
Published: May 2020

8033 Background: classical Hodgkin lymphoma (cHL) are characterized by genetic alterations at the 9p24·1 locus and PD-L1 ligand overexpression. GLS-010 is a novel fully human anti-PD-1 mAb and exhibited favorable result in previous Phase I study. This multi-center, single-arm Phase II clinical trial is aimed to further evaluate the safety and efficacy profile of GLS-010 in Chinese patients (pts) with relapsed or refractory cHL. Methods: All pts enrolled received GLS-010 240mg every 2 weeks until disease progression, death, unacceptable toxicity or withdraw from the study. The primary endpoint was objective response rate (ORR) by independent review committee (IRC) per Lugona 2014. Adverse events (AEs) were graded by NCI CTCAE v4.03. Results: 85 pts with relapsed or refractory cHL who had received at least 2 lines of prior systemic chemotherapies were enrolled and treated. As of August 2 2019, data cutoff, pts received a median of 8 treatment cycles (1 cycle include 2 injections), with 12 pts discontinued and 73 pts were still in treatment. At a median follow-up of 6.57 months, an ORR was reported in 78 of 85 patients (91.76%, 95%CI, 83.77-96.62), by an IRC assessment, including 30(35.3%) pts with a complete response (CR) and 48 pts (56.5%) with a partial response (PR). Median duration of response (DoR) and progression free survival (PFS) were not reached yet. Treatment-related adverse events (TRAEs) of any grade occurred in 77 (90.6%) of 85 patients, most of which were Grade 1-2.The most common TRAEs were fever (26/85, 30.6%), neutrophil count decreased (16/85, 18.82%), white blood cell count decreased (15/85, 17.65%). ≥ Grade 3 TRAEs occurred in 23 (27.06%) pts, most commonly, hepatic function abnormal (5/85, 5.88%), hyperuricaemia (4/85, 4.71%). Conclusions: GLS-010 showed impressive anti-tumor activity (ORR = 91.96%) and manageable safety profile in Chinese patients with relapsed or refractory cHL, which could be a new safe and effective treatment option in this setting. Clinical trial information: NCT03655483 .
Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Long-term 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 , Zuo Hongli 
Published: May 2020

8034 Background: 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 profile after long-term 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 objective response rate (ORR) by an independent radiological review committee (IRRC) per IWG 2007 has been reported before. The progression free survival (PFS) by IRRC follow-up data are reported herein. Results: 96 patients were treated. As of the data cutoff on 30 Sep, 2019, 57.3 % patients complete two-year treatment, with a median follow-up of 26.7 months. The median duration of treatment was 24.1 months (range: 0.7 to 24.8). Of 49 patients with progressive disease (PD) by investigator, 39/49 (79.6%) patients received treatment beyond PD, with a median treatment duration after PD of 8.0 months (range: 1.4 to 20.8). The median PFS was 18.6 months (95%CI: 14.4 to 22.3). Median overall survival has not been reached. Two-year OS rate was 96.3% (95%CI: 88.9% to 98.8%). The treatment-related adverse event (TRAE) was reported in 92/96 (95.8%) patients, most (71/96, 74.0%) of which were grade 1-2. The most common grade 3 or 4 TRAEs were pyrexia (3/96, 3.1%), lipase increased (3/96, 3.1%) and lymphocyte decreased (3/96, 3.1%). Conclusions: The results from long-term follow-up showed that, in addition to a high rate of response, sintilimab also demonstrated durable efficacy and favorable long-term safety profile. Considering the high rate (nearly 80%) of treatment beyond PD, IWG 2007 which was used to evaluate PFS may not be a suitable criteria for evaluating the efficacy of anti-PD-1 antibody in cHL. Further investigation and analysis are required. Clinical trial information: NCT03114683 .
Outpatient treatment with lisocabtagene maraleucel (liso-cel) across a variety of clinical sites from three ongoing clinical studies in relapsed/refractory (R/R) large B-cell lymphoma (LBCL).
Authors: Bachier Carlos R. , Godwin John E. , Andreadis Charalambos , Palomba Maria Lia , Abramson Jeremy S. , Sehgal Alison R. , Hildebrandt Gerhard , Stevens Don A. , Hoda Daanish , Licitra Edward J. , Siddiqi Tanya , Farazi Thalia Andrea , Kostic Ana , Trede Nikolaus S. , Wang Lei , Lymp James , Maloney David G. 
Published: May 2020

8037 Background: Currently approved CAR T cell therapies are generally administered as inpatient (inpt) treatment at university medical centers due to concerns about frequency, onset, severity, and management of AEs, including cytokine release syndrome (CRS) and neurologic events (NEs). We sought to characterize whether patients (pts) could be safely monitored in the outpatient (outpt) setting after receiving liso-cel, an investigational, CD19-directed CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, across university and non-university sites in TRANSCEND NHL 001 (NCT02631044), OUTREACH (NCT03744676), and PILOT (NCT03483103). Methods: Eligible pts had R/R LBCL after systemic chemoimmunotherapy; moderately impaired organ function was allowed. For outpt infusion of liso-cel, pts were required to receive safety monitoring education, have a caregiver and stay within 1 h travel to site of care for 30 d post-treatment. All study sites had a multidisciplinary CAR T cell team and standard operating procedures for toxicity monitoring and management. Results: At data cutoff, 53 pts had received liso-cel on Study Day 1 and were monitored as outpts (university, n = 33; non-university, n = 20), including pts ≥65 y of age (n = 23) and with high tumor burden (SPD ≥50 cm2; n = 16). Any grade CRS and NEs were reported in 18 (34%) and 14 pts (26%), respectively. Severe CRS and/or NEs occurred in only 2 pts (4%) and were reversible. Median (range) time to onset of CRS and NEs was 5 (2–9) and 8.5 (3–22) d, respectively. Tocilizumab and/or corticosteroids for treatment of CRS and/or NEs were required in 8 pts (15%). Overall, 30 pts (57%) required hospitalization post-treatment, with a median (range) time to hospitalization post-treatment of 5.5 (2–22) d; 9 pts (17%) were hospitalized Study Day 4 or earlier. Two pts required ICU-level care. There were no grade 5 treatment-emergent AEs. Safety in pts monitored as outpts was comparable across types of sites. Overall response rate was 81% (95% CI, 68–91). Safety and efficacy were consistent with data from inpts across the 3 studies (N = 270). Conclusions: Pts with R/R LBCL were successfully treated with liso-cel and monitored for CAR T cell-related toxicity in the outpt setting across different types of sites. Incidences of severe CRS, NEs, and early hospitalization were low; 43% of pts did not require hospitalization. A larger dataset will be presented, including comparisons of outpts vs inpts and sites of care. Clinical trial information: NCT02631044 (TRANSCEND NHL 001), NCT03744676 (OUTREACH), NCT03483103 (PILOT) .
Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: Results of induction therapy in Alliance 51101.
Authors: Batchelor Tracy , Giri Sharmila , Ruppert Amy S. , Bartlett Nancy L. , Hsi Eric D. , Cheson Bruce D. , Nayak Lakshmi , Leonard John Paul , Rubenstein James L. 
Published: May 2020

8042 Background: Optimal consolidative therapy for primary central nervous system lymphoma (PCNSL) is not defined. Avoidance of whole brain radiation may reduce risk of neurotoxicity. Non-radiation consolidative options include myeloablative chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) or non-myeloablative chemotherapy. Methods: This is a randomized phase 2, National Clinical Trials Network study of induction methotrexate (MTX) (8 g/m2days 1, 15), temozolomide (TMZ) (150-200 mg/m2 D7-11), and rituximab (RTX) (C1 D3, 10, 17, 24 and C2 D3, 10) in four 28-day cycles followed by one cycle of cytarabine (ARA-C) (2 g/m2 BID, D1, 2) (MTRA). Following induction, patients (pts) received consolidation with thiotepa (5 mg/kg BID, D -5, -4) plus carmustine (400 mg/m2, day -6) and ASCT (Arm A) or one cycle of ARA-C (2 g/m2 BID, D1-4) plus infusional etoposide (40 mg/kg over 96h) (Arm B). The primary endpoint was median progression-free survival (PFS), designed to compare consolidation regimens. This report describes the results of the 5 cycles of induction therapy. Results: 113 pts (median age 61 years, range 33-75) were randomized (Arm A: 57, Arm B: 56) across 27 centers. 108 eligible pts who received induction therapy were evaluated. 36 pts (33.3%) did not proceed to consolidation, mainly due to disease progression (17), pt withdrawal (8), or adverse events including death (6). Grade 3 or 4 febrile neutropenia occurred in 12 pts (11.1%) during induction. Dose modifications of MTX were required in 75% of pts and 63.3% of cycles, mainly due to renal adjustments. Dose delays of MTX were required in 52.8% of pts and 22.2% of cycles. Overall response rate (CR, CRu, PR) at the end of induction was 65.7% (95% CI, 56%, 74.6%). Conclusions: While MTRA is feasible and active a significant proportion of pts did not receive consolidation, supporting the need to develop more effective induction strategies. Clinical trial information: NCT01511562 .
Treatment stratification in B-cell PTLD after solid organ transplantation (SOT) by international prognostic index (IPI) and response to rituximab: Interim results from the PTLD-2 trial.
Authors: Trappe Ralf Ulrich , Koenecke Christian , Dreyling Martin H. , Pott Christiane , Duehrsen Ulrich , Meidenbauer Norbert , Hahn Dennis , Heuser Michael , Schmidt Christian , Ritgen Matthias , Siebert Reiner , Oschlies Ilske , Anagnostopoulos Ioannis , Zimmermann Heiner ,   DPTLDSG and GLA
Published: May 2020

8045 Background: The PTLD-1 trials have established risk-stratified sequential treatment of B-cell PTLD. After rituximab induction, patients (pts) in complete remission (25 %) received rituximab consolidation, while all others received R-CHOP. The PTLD-2 trial tests modified risk-stratification including clinical risk factors. These are the results of the 2nd scheduled interim analysis (40/60 planned pts). Methods: The prospective, multicenter phase II PTLD-2 trial (NCT02042391) enrols treatment-naïve adult SOT recipients with CD20-positive PTLD. Key exclusion criteria are CNS involvement, ECOG > 2, pregnancy, and severe organ dysfunction or severe, active infection. Treatment consists of rituximab (1400 mg SC; first application 375 mg/m2 IV) on days 1, 8, 15 and 22. After restaging, pts in CR as well as those in PR with ≤ 2 IPI risk factors at diagnosis (low-risk group) continue with four three-weekly courses of rituximab. Most other pts (high-risk group) receive 4 cycles of R-CHOP-21, while thoracic SOT recipients who progress under rituximab (very-high-risk group) receive six cycles of alternating R-CHOP-21 and R-DHAOx. The primary endpoint (event-free survival in the low-risk group) is not analyzed here. Secondary endpoints presented here are response and overall response (ORR) by computed tomography, overall survival (OS), time to progression (TTP) and treatment-related mortality (TRM) overall and by risk group. Results: 40 pts were recruited at 12 centers (2015 – 2019). 21/40 were kidney, 11 lung, 4 liver, 3 heart, and 1 liver/kidney transplant recipients. Median age was 54 years. 38/40 PTLD were monomorphic and 15/40 EBV-associated. 38 pts were evaluated for response at interim staging: 13 were allocated to the low-risk, 17 to the high-risk and 8 to the very-high-risk group. ORR was 28/30 (93 %, CR: 16/30 [53 %]). With a median follow-up of 1.9 years, the 1-year/3-year Kaplan-Meier (KM) estimates of TTP and OS in the intention-to-treat population (40 pts) were 85 %/80 % and 70 %/70 %, respectively. In the low-risk group, the 2-year KM estimate of OS was 100 %. The frequency of infections (all grades) was 50 %, and TRM occurred in 3/40 pts (8 %). Conclusions: One third of enrolled pts were treated in the low-risk group and the recruitment goal for evaluation of the primary endpoint will likely be reached. Interim efficacy and toxicity data with rituximab SC and modified risk-stratification are encouraging despite the inclusion of 35 % thoracic SOT recipients. Clinical trial information: NCT02042391 .