bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of SF3B1 mutation on outcomes in myelofibrosis.
Authors: Bose Prithviraj , Senapati Jayastu , Masarova Lucia , Pemmaraju Naveen , Bravo Guillermo Montalban , Pierce Sherry , Zhou Lingsha , Garcia-Manero Guillermo , Kantarjian Hagop M. , Verstovsek Srdan 
Published: June 2022

e19080 Background: Splicing factor 3B subunit 1 ( SF3B1) mutations have been shown to confer a unique phenotype in MDS and MDS/MPN overlap syndromes, with ring sideroblasts, thrombocytosis and favorable prognosis. In myelofibrosis (MF) the frequency of SF3B1 mutation is <10% and may play a less important role in disease outcomes (Lasho et. al, Leukemia, 2011). Methods: We retrospectively analyzed all patients (pts) with WHO-defined MF (primary, including pre-fibrotic MF, or progressed from PV or ET) seen at our center from Jan. 2017 through Jul. 2021. We compared disease phenotypes, MPN driver and co-occurring mutations, cytogenetics, dynamic IPSS (DIPSS) score, transfusion requirements, treatment characteristics and survival outcomes between patients with SF3B1-mutated ( SF3B1+) and -wild type ( SF3B1-) MF. Results: A total of 381 pts were identified, 29 (8%) of whom were SF3B1+. There were similar frequencies of JAK2, CALR, MPL mutations and “triple negative” MF in the 2 groups (Table). The median number of SF3B1 mutations was 1 (range, 1-2); K666N being the most common (52%). The 2 groups were similar in regard to their baseline hemoglobin, white blood cell counts, platelets, co-occurring mutations, symptom burden and DIPSS but more SF3B1+ pts were PRBC transfusion-dependent at presentation than SF3B1- pts (38% vs. 15%, p=0.003). At a median follow up of 17.2 months for the entire cohort (range, 0.1- 52.2 mos., 22.6 mos. for SF3B1+ and 16.8 mos. for SF3B1-), 41 pts had died [14% SF3B1+ and 10% SF3B1-, p=0.5] and 7 pts (1 SF3B1+ and 6 SF3B1-) had leukemic transformation. The median estimated OS was 230 months for SF3B1- vs. not reached for SF3B1+ pts (p = 0.6). Conclusions: SF3B1 mutation is an uncommon event in MF and does not substantially affect disease phenotype and outcomes. MF pts with SF3B1 mutation are more likely to be PRBC transfusion dependent.[Table: see text]
Venetoclax combined with cladribine in patients with relapsed/refractory (R/R) T-cell prolymphocytic leukemia (T-PLL).
Authors: Arani Naszrin , Jammal Nadya , Geppner Alexis , Kim Kunhwa , Borthakur Gautam , Jain Nitin , Konopleva Marina , Garcia-Manero Guillermo , Ferrajoli Alessandra , Jabbour Elias , Kantarjian Hagop M. , Kadia Tapan M. 
Published: June 2022

e19087 Background: T-cell prolymphocytic leukemia (T-PLL) is an ultra-rare and aggressive mature T-cell leukemia associated with a poor prognosis. First-line therapy is with CD52 monoclonal antibody alemtuzumab and allogenic stem cell transplant (SCT), but treatment is rarely curative. There is a critical need for more active therapies to improve outcomes. The BCL-2 inhibitor venetoclax (VEN) has demonstrated activity in T-PLL. We studied a combination of cladribine plus VEN in 5 patients (pts) with R/R T-PLL to investigate the safety and efficacy of this combination. Methods: We retrospectively analyzed pts ≥ 18 years with R/R T-PLL treated with a backbone of cladribine 5 mg/m2 intravenous (IV) for 5 days with VEN at a target dose of 600-800 mg orally daily (reduced for concomitant drug interactions) on a 28-day cycle. Two pts concomitantly received alemtuzumab, 1 received ruxolitinib, and 2 pts received both. Baseline demographics, cytogenetics and mutations were collected and summarized using descriptive statistics. Response criteria were defined according to the T-PLL consortium and survival analyzed by Kaplan-Meier method. Results: Five pts with a median age of 64 years (range, 59-66) were treated with cladribine + VEN. Pts had a median of 1 prior therapy (range, 1-3), including 3 (60%) with prior SCT. Overall response rate was 100%, including 2 (40%) complete remission with incomplete count recovery (CRi) (with 1 MRD negative CR), and 3 (60%) partial response (PR). A median of 2 cycles were given (range, 1-4). Baseline characteristics are summarized in Table. All five pts had abnormalities of chromosomes 8, 14, and TCL-1 (positive by FISH); 3 had a STAT5B mutation and 1 each had mutations in JAK1, JAK3, and IL7R. Pts had rapid reductions in all T-PLL-related symptoms and signs (i.e., WBC, splenomegaly, effusions, skin lesions, nodes) within the 2 weeks of starting. The regimen was well-tolerated. Two pts had transient grade 1 creatinine elevations and 4 had grade 4 neutropenia that returned to baseline in a median of 67 days (range, 2-93 days). At the time of data review, 1 patient was alive at 8.3 months. The median overall survival (OS) was 5.8 months. Conclusions: The combination of cladribine and VEN in patients with T-PLL refractory to first-line alemtuzumab was well-tolerated and effective. It was associated with rapid disease control, including splenomegaly, fatigue, pleural infiltrates, and skin infiltration. Staging studies to be presented. This encouraging experience should prompt further study as salvage therapy for T-PLL.[Table: see text]
Survival outcome of patients with relapsed or refractory classical Hodgkin lymphoma who achieved remission during immune checkpoint inhibitors treatment.
Authors: Liu Weiping , Lin Ningjing , Xie Yan , Wang Xiaopei , Song Yuqin , Zhu Jun 
Published: June 2022

e19531 Background: Immune checkpoint inhibitors (ICIs) showed strong activity and tolerable toxicity in those patients with relapsed or refractory classical Hodgkin lymphoma. However, there was limited data on the long-term survival outcome of those patients after remission due to ICIs treatment. Methods: The data was collected from 4 pivotal phase 2 clinical trials: AK105-201 (penpulimab, NCT03722147), BGB-A317 (tislelizumab, NCT03209973), SHR-1210 (camrelizumab, NCT03155425), GLS-010 (zimberelimab, NCT03655483). The key inclusion criteria included age ≥18 years, relapsed or refractory classical Hodgkin lymphoma, lines of prior chemotherapy ≥ 2, treated with ICIs monotherapy, achieving complete remission (CR) or partial remission (PR). The progression-free survival (PFS) and overall survival (OS) were estimated from the time of registration. Results: Among 324 screened patients, 260 patients (140 with CR, 120 with PR) were enrolled. The median age was 32 years with a male/female ratio of 1.3:1. The median lines of prior chemotherapy was 3 (range, 2-11). Additionally, 184 patients had refractory disease, and 54 patients received autologous stem cell transplantation (n = 45) or brentuximab vedotin (n = 9). With a median follow-up period of 31.1 months, 116 (44.6%) patients underwent disease progression and 18 (6.9%) patients died. The 3-year PFS and OS rates of 55.1% and 89.7% for all patients, respectively. Compared with those with CR, patients with PR had inferior survival outcome (3-year PFS, 29.5% vs. 72.3%, P < 0.001; 3-year OS, 81.5% vs. 94.4%, P = 0.017). In terms of duration of treatment, the 3-year PFS and OS rates were 28.6% and 71.6%, and 74.5% and 98.5% for patients with duration of treatment < 24 and > 24 month, respectively ( P values were both < 0.001). Among patients with CR, longer duration of treatment (> 24 month) remained positive impact on the survival outcome (3-year PFS, 81.3% vs. 47.1%, P < 0.001; 3-year OS, 98.1% vs. 82.9%, P < 0.001). Conclusions: Deeper remission and longer duration and led to favorable survival outcome for patients with relapsed or refractory classical Hodgkin lymphoma who achieved remission during ICIs treatment.
Combined modality therapy for early-stage Hodgkin lymphoma in the PET era: A real-world study.
Authors: Chohan Karan , Young Jason R. , Lester Scott , Alhaj Moustafa Muhamad , Rosenthal Allison Claire , Tun Han W. , Hoppe Bradford , Johnston Patrick B. , Micallef Ivana N. M. , Habermann Thomas Matthew , Ansell Stephen M. 
Published: June 2022

e19532 Background: The traditional approach to the treatment of early-stage classical Hodgkin lymphoma (cHL) has been combined modality therapy (CMT) with both chemotherapy and radiotherapy (RT). CMT has shown improved disease control, but RT can lead to long-term adverse effects, including secondary malignancies and cardiac toxicity. Multiple clinical trials have assessed treatment de-escalation strategies to chemotherapy-alone regimens, but results are conflicting. We aimed to assess the real-world implications of these trials by comparing patient outcomes based upon treatment with CMT or chemotherapy-alone. Furthermore, we proposed to assess differences in treatment outcomes stratified by disease bulk, favorable/unfavorable disease, and PET2 response. Methods: We conducted a retrospective, multi-center cohort study of consecutive adult patients with early-stage (stage IA-IIB) cHL treated between January 2010-December 2020. Baseline characteristics, treatment modality, and outcomes were abstracted by chart review. Available PET2 scans (n=110) were independently reviewed by a blinded nuclear radiologist. Deauville score (DS) ≥4 was characterized as positive (+), and DS≤3 negative (-). All analysis was conducted using intention-to-treat principles based upon the initial treatment plan (CMT or chemotherapy-alone). Results: In 125 patients [58% male, median age 34 (range, 18-78)] with early-stage cHL, CMT was intended in 63 (50%) patients, with chemotherapy-alone in 62 (50%). Bulky disease was observed in 43 (34%), unfavorable disease in 81 (65%), and 15 (14%) were found to be PET2+. With median follow-up of 59.8 months (95%CI, 48.6 to 71.0), 5 (4%) deaths occurred, and 17 (14%) patients had relapsed/refractory disease. No significant differences in overall survival (OS) were seen based upon treatment intention. However, there was substantially reduced progression-free survival (PFS) (Table) with chemotherapy-alone in the whole cohort, and also in those with bulky, unfavorable, and PET2+ disease. No significant PFS differences were seen based upon treatment intention for patients with non-bulky, favorable, or PET2- disease. Conclusions: Based on our real-world experience, CMT appears particularly beneficial for patients with bulky disease, unfavorable prognostic factors, and PET2+ disease. However, while recent trials showed a benefit of CMT in non-bulky, favorable and PET2- patients, chemotherapy-alone may be comparable for these patients in actual clinical practice.[Table: see text]
PJP pneumonia in brentuximab vedotin recipients.
Authors: Scheckel Caleb , Abeykoon Jithma P. , Childs Daniel S , Higgins Alexandra , Hwang Steven Ray , Barreto Jason , Ansell Stephen M. , Bennani Nabila Nora 
Published: June 2022

e19533 Background: Pneumocystis pneumonia (PJP) is a catastrophic infection seen in the context of low CD4 counts. Brentuximab vedotin (BV) is a drug antibody conjugate targeting CD30 and is used to treat patients with Hodgkin’s lymphoma (HL) and T-cell lymphoma (TCL). PJP prophylaxis is not currently recommended for patients receiving BV-based treatment despite co-expression of CD30 on CD4 cells. The frequency of PJP following BV remains poorly defined. Methods: We evaluated patients who received BV between January 1, 2011 and October 31, 2021 at Mayo Clinic for the development of PJP. Patient demographics and clinical characteristics including underlying disease, chemotherapy regimen, absolute lymphocyte count (ALC), and steroid exposure were collected. Patients who developed PJP more than 3 months after their last BV exposure were excluded. Results: Of 402 BV recipients identified, 63 received PJP prophylaxis and were omitted. Fourteen of the 339 (4.1%) not on prophylaxis developed PJP following BV. Those infected had a median age of 61 (22-87), 71% were male. The most common diagnoses were HL, TCL, and primary mediastinal B-cell lymphoma at rates of 57%, 21%, and 14% respectively. Therapy regimens included BV monotherapy, BV-CHP, and BV-AVD at rates of 43%, 21%, and 14% respectively. BV represented median 2nd line of therapy (1-10) and patients received median of 3 doses (1-10) prior to PJP diagnosis. Patients with PJP had median ALC of 620 (370-3500). 71.4% (10/14) had an ALC less than 750 and among those with ALC greater than 1000, 75% (3/4) had underlying diagnosis of HL. Three patients had CD4 count measured at time of PJP diagnosis with median value of 157 (5-175). 57.1% (8/14) had no steroid exposure beyond the treatment regimen. 14.3% (2/14) were on chronic doses of 5mg prednisone for autoimmune conditions. Short bursts of steroids (prednisone 40 mg) prior to PJP were seen in 21.4% (3/14) with median exposure of 8 days (7-10). One patient had prolonged steroid exposure but was weaned off 17 days prior to PJP diagnosis. 71.4% were older than 50 years at time of PJP. Conclusions: We observed rates of PJP above the commonly accepted threshold of 3.5% for recommending prophylaxis. Among patients with an ALC greater than 1000, 75% had HL raising the question of a qualitative defect in immunity. Close ALC monitoring is recommended for patients receiving BV with a low threshold to institute PJP prophylaxis, especially amongst those older than 50 or with a diagnosis of HL.[Table: see text]
Clinical applicability of targeted next-generation sequencing for precision medicine in diffuse large B-cell lymphoma.
Authors: Huang Dehong , Liu Yao , Li Jieping , Yang Tao , Liu Jun , Xiao Chunyan , Guo Bingling , Wu Jing , Liang Xiping , Zhang Wenjun , Luo Xin , Zhang Lingqian , Xiang Ying , Li Qiying , Nan Yingyu , Wang Xiaoxuan , Du Furong , Song Chao 
Published: June 2022

e19538 Background: Comprehensive genomic analysis based on next-generation sequencing (NGS) allows a better molecular characterization of diffuse large B-cell lymphoma (DLBCL), offering a roadmap toward precision medicine. Methods: We analyzed somatic alterations of 37 DLBCL tissue or blood samples by a hybridization capture-based NGS panel targeting 188 lymphoma-related genes. Results: Totally, 279 single-nucleotide variants and small insertions or deletions affecting 103 genes were identified, with at least 1 mutation detected in 100% (37/37) of cases. The most frequently mutated genes were those involved in epigenetic modifiers ( DNMT3A, KMT2B and KMT2D), activated signaling ( TYK2, MYD88, NOTCH2 and BCR) and transcription factors/transcriptional regulator ( RUNX1, SPEN, IRF4, KLF2 and ASXL1). Significant co-occurrences were shown between RUNX1 mutations with NOTCH2, IRF4, ARID1A and BCR ( P< 0.05, respectively), BCR and IRF4 ( P< 0.01), etc. Additionally, we analyzed the association of genomic aberrations with clinicopathological features in DLBCL. Patients aged > 60 years harbored less LRP1B mutations than those aged ≤60 years (5.3% vs. 33.3%, P< 0.05). The mutation frequency of TP53 was significantly higher in LDH-high (> 244 U/L) group than that in LDH-low (≤244 U/L) group (40% vs. 6.25%, P< 0.05). Compared with germinal center B-cell (GCB), the mutation frequency of TYK was significantly lower in non-GCB (5% vs. 36.4%, P< 0.05). New potential therapeutic targets ( CREBBP, EP300, EZH2, SMARCB1, CD79A/B, BTK, CARD11, MYD88, THFAIP3, PIK3CA, PTEN and JAK) were identified in 55% (11/20) of newly diagnosed patients and in 41.2% (7/17) of relapsed/refractory patients. Ibrutinib, as a single agent, has demonstrated limited activity in DLBCL with mutant MYD88 and wildtype CD79. In this study, we identified 3 patients with mutant MYD88 and wildtype CD79A/B (8.1%), among whom 2 harbored MYD88 L265P variants and 1 had MYD88 S219C mutation. Conclusions: The utility of mutational profiling may facilitate the identification of potential drug targets, which in turns may represent new therapeutic possibilities.
Relma-cel (JWCAR029) in relapsed and refractory B-cell non-Hodgkin lymphoma: A two-year survival update of a phase I study.
Authors: Ying Zhitao , Song Yuqin , Zhu Jun 
Published: June 2022

e19555 Background: B-cell non-Hodgkin lymphoma (B-NHL) has a very poor prognosis. Relma-cel (JWCAR029) is a CD19-targeted chimeric antigen receptor T (CAR-T) cell suspension. In a phase I trial performed in November 2017 in Beijing Cancer Hospital, China, JWCAR029 was used to treat relapsed/refractory B-NHL (R/R B-NHL) in adult patients, showing a high response rate and persistent response. This report aimed to update 2-year survival data generated in the above trial. Methods: This was an open-label, dose-escalating phase I study (JWCAR029-001, NCT03344367) involving patients with R/R B-NHL. The patients received a 3-day treatment with the conditioning chemotherapy regimen, consisting of fludarabine (25 mg/m2/day) and cyclophosphamide (250 mg/m2/day). Then, they received a single dose of intravenous JWCAR029 (25×106, 50×106, 100×106, or 150×106 CAR T cells). Two-year PFS and OS after JWCAR029 treatment were evaluated. The data were updated till the cut-off date of January 18, 2021. Results: A total of 23 patients with R/R B-NHL were enrolled, of whom 22 completed single-dose JWCAR029 cell infusion. All patients completed the 2-year follow-up, with a median time of 24.2 (95%CI 24.0-24.3) months. Based on the efficacy analysis set comprising 20 patients, the best ORR and CRR were 85.00% and 70.00%, respectively. In subgroup analysis, 1-year ORR and CRR in patients administered 100×106 cells were both 3/5 (60%); they were both 5/8 (62.5%) in those administered 150×106 cells. The 1-year and 2-year PFS rates (11 patients censored) were both 55.0%. Median PFS was not reached (95%CI 3.0 months-NA). The 1-year and 2-year PFS rates in patients administered 100×106 cells were both 60.0%; these values were both 62.5% in individuals treated with 150×106 cells. The 1-year and 2-year OS rates (3 patients censored) were both 68.6%. Median OS was not reached (95%CI 10.4 months-NA). The 1-year and 2-year OS rates in patients administered 100×106 cells were both 60.0%; these values were both 75.0% in those treated with 150×106 cells. A total of 6 patients (30%) died. No grade 3 and above CRS or NT were found. Conclusions: JWCAR029 was approved in China in September 2021 after the RELIANCE study (NCT04089215) reported its excellent efficacy and tolerable toxicity in the treatment of relapsed/refractory B-cell lymphoma. This report indicated that R/R B-NHL cases could benefit from JWCAR029. R/R B-NHL cases administered JWCAR029 at 100×106 or 150×106 cells had a promising response rate, with durable PFS and sustained OS benefits after 12 months. The effectiveness and safety of JWCAR029 need to be confirmed in the real-world setting. Clinical trial information: NCT03344367.
Efficacy and safety of orelabrutinib in diffuse large B-cell lymphoma: A real-world analysis.
Authors: Xu Peng-Peng , Liu Tingbo , Li Zengjun , Li Zheng , Huang Wei , Zhou Keshu , Cai Mingci , Shen Rong , Zhao Weili 
Published: June 2022

e19556 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Recently, based on in-depth genomic analysis, new taxonomies for DLBCL have been proposed. Genetic subtype MCD is predominantly enriched with B-cell receptor-dependent NF-κB activation and well responded to Bruton’s tyrosine kinase (BTK) inhibitors. Ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) proved the efficacy in patients with MCD DLBCL in PHOENIX study. Orelabrutinib is a novel BTK inhibitor with excellent target selectivity. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing regimens for the treatment of patients with MCD DLBCL in a real-world setting. Methods: Eligible patients with pathologically confirmed MCD DLBCL, regardless previous treatment, were included from 6 centers between January and December 2021. All patients received orelabrutinib-containing regimens and underwent at least one treatment response evaluation. Patients with known CNS lymphoma and primary mediastinal lymphoma were excluded. The primary endpoint was complete response rate (CRR) assessed by investigator using PET-CT per the 2014 Lugano Response Criteria for Non-Hodgkin Lymphoma. Safety was assessed by adverse events (AEs) referring to Common Terminology Criteria for AEs version 5.0. Results: Fourteen patients (10 males) were included. The median age was 66 (range 45-77) years, and 35.71% (5/14) documented ≥2 extranodal involved sites. Most patients had an Eastern Cooperative Oncology Group score of 0-1 (9/14, 64.29%), Ann Arbor Stage III-IV disease (11/14, 78.57%), elevated lactate dehydrogenase (9/14, 64.29%), and International Prognostic Index score ≥3 (8/14, 57.14%). All patients received orelabrutinib 150 mg once daily. Among them, 8 (57.14%) were treated with R-CHOP or rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) as first-line therapy, and 6 (42.86%) with rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), R-CHOP or rituximab with lenalidomide as second-line therapy. The CRR for the first-line and second-line therapy were 75.00% and 66.67%, respectively. The most common AEs were hematologic (platelet count decrease, white blood count decrease or lymphocyte count decrease), and non-hematologic AE was infection (urinary or respiratory). Reported AEs were generally manageable and resolved soon after supportive treatment. AEs associated with off-target activities such as atrial fibrillation, diarrhea, and major hemorrhage were not reported. Conclusions: Orelabrutinib-containing regimens demonstrated encouraging efficacy and well-tolerated safety profile among patients with MCD DLBCL. A large-scale prospective clinical study is on registration, which would offer a new potential therapeutic option for patients with MCD DLBCL.