Kooperativer Bibliotheksverbund

In: Asia-Pacific Journal of Oncology Nursing, Elsevier BV, ( 2023-11), p. 100335-

Type of Medium: Online Resource

ISSN: 2347-5625

URL: Article

DOI: 10.1016/j.apjon.2023.100335

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2984639-0

In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-09-11)

Abstract: The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-023-41928-2

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2615211-3

In: Healthcare Quarterly, Longwoods Publishing, Vol. 14, No. 4 ( 2011-11-3), p. 78-80

Type of Medium: Online Resource

ISSN: 1929-6347

URL: Issue

URL: Journal

URL: Article

DOI: 10.12927/hcq.2013.22591

DOI: 10.12927/hcq

DOI: 10.12927/hcq.2011.22655

Language: Unknown

Publisher: Longwoods Publishing

Publication Date: 2011

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 15-16

Abstract: Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Castillo JJ, Am J Hematol. 2008) There has been a paucity of data suggesting that limited stage disease (Ann Arbor stage I-II) may have a more favorable prognosis. However, due to the rarity of this disease there have been no large-scale reviews to confirm this. Thus, many patients with limited stage disease are subject to the aggressive therapy recommendations based on the poor outcomes of PBL patients as a whole. (Loghavi S, J Hematol Oncol. 2015; NCCN Guidelines, version 2.2020; Al-Malki MM, BBMT. 2014) We attempted to determine the treatment patterns and outcomes of patients with limited stage PBL. Methods: We conducted a multi-center (13 US academic centers) retrospective study of patients with limited stage (Ann Arbor stage I-II) Plasmablastic lymphoma. Determination of limited stage and diagnosis of PBL was determined by the investigators at each individual center. Patients diagnosed between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcomes data were extracted by retrospective chart review. Kaplan Meier was utilized for time to event analysis. Results: Baseline characteristics are included in table 1. A total of 80 patients were identified with limited stage disease. With a median follow up of 34 months the 3-yr Progression free survival (PFS) and overall survival (OS) was 71.9% and 78.7% respectively (Figure 1A and 1B). Patients that received frontline chemotherapy with (n=29) and without RT (n=36) had a 3-yr PFS and OS of 84.6% and 96.2% as compared to 64.5% and 70.8%, respectively (Figure 2A and 2B; Figure 3A and 3B). The Hazard ratio (HR) for PFS and OS for chemo (reference) vs chemo-RT was 0.47 (95% CI 0.18-1.3; P=0.131) and 0.18 (95% CI 0.04-0.84; p=0.029) respectively. The HR for PFS and OS for CHOP (n=14, reference) vs EPOCH (n=33) based regimens was 0.37 (95% CI 0.11-1.2; p=0.106) and 0.36 (95% CI 0.079-1.6; p=0.182) respectively. Patients with stage I/IE disease (n=56) had a 3-yr PFS and OS of 73.1% and 81.2% respectively. Patients with stage II/IIE disease (n=24) had a 3-yr PFS and OS of 69.3% and 73.4% respectively. Patients that received aggressive treatment (n=17) with Hyper-CVAD based regimens and/or Auto-SCT as consolidation had a 3-yr PFS and OS of 63.6% and 72.7% respectively. Patients with concomitant HIV (n=16) had a 3-yr PFS and OS of 80.8% and 77.4% respectively. Seven patients received RT alone and 6 patients had surgical resection alone as frontline therapy; 1 patient received no therapy; 1 patient received HAART therapy only and remains in CR without any other treatment for PBL 29 months after diagnosis. There were 8 deaths (10%) related to PBL, 3 deaths (4%) related to treatment of PBL (2 during frontline chemo and 1 upon relapse with salvage chemo), and 9 deaths (11%) related to other causes. The 3-yr lymphoma free survival (LFS) of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (without including treatment related mortality (TRM) as an event) was 89.1%, 85.2%, and 100% respectively. The 3-yr LFS survival of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (including TRM as an event) was 85.1%, 80.0%, and 96.2% respectively. Discussion: Here we report the largest review to our knowledge of limited stage PBL. Outcomes appear to be excellent with 3-yr PFS and OS of 71.9% and 78.7% respectively and a 3-yr LFS of 89.1% (85.1% when attributing TRM as an event). There was no obvious benefit to receiving aggressive therapy with H-CVAD based regimens and/or Auto-SCT. Although this is a small, uncontrolled sample size the HR for OS was improved in patients receiving frontline chemo-RT vs chemo alone 0.18 (95% CI 0.04-0.84; p=0.029). However, this did not take into account TRM with or progression while receiving frontline chemotherapy. Patients who were HIV+ had similar PFS and OS outcomes compared to the entire cohort. This retrospective study clearly demonstrates the favorable outcomes in this patient population, especially in those able to receive definitive therapy for their disease. Disclosures Hess: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Chavez:Bayer: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Verastem: Consultancy; Pfizer: Consultancy. Hill:Beigene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Maddocks:Pharmacyclics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; OncLive: Honoraria. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Janssen Scientific: Consultancy, Other; Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; NCI: Research Funding. Portell:Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Takeda: Research Funding; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau. Castillo:TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-138536

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1425-1425

Abstract: Introduction. The optimal treatment of patients with diffuse large B cell (DLBCL) and high-grade B cell (HGBCL) lymphomas with synchronous central nervous system (CNS) and systemic involvement at diagnosis is not well defined. High-dose methotrexate (MTX) administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited. Methods. We included consecutive patients with DLBCL and HGBCL with synchronous CNS and systemic involvement at diagnosis treated with RM-CHOP from 1/2012 - 1/2021. Progression-free survival (PFS) was calculated from the time of diagnosis to either progression or death, and overall survival (OS) from the time of diagnosis to death due to all causes; patients without events were censored at the time of the last follow-up. PFS and OS were estimated through the Kaplan-Meier method. Results. Fifty patients were included. Median age was 62 years (range, 19 - 80), 58% were male, 82% had DLBCL (n=41) and 18% had HGBCL (n=9). Six patients (14%) had MYC with BCL2 and/or BCL6 rearrangements by fluorescence in situ hybridization (available for n=43), and 11 patients (55%) had MYC and BCL2 double-expression by immunohistochemistry (available for n=20). ECOG performance status was ≥2 in 16 patients (36%). LDH was elevated in 41 patients (87%).The IPI score classified 40% and 56% of patients as having intermediate- or high-risk disease, respectively. The median number of extranodal sites was 2 (range, 1-7) with 48% having ≥3 extranodal sites. CNS involvement was parenchymal in 14 patients (28%), leptomeningeal in 28 (56%), or both in 8 (16%). The most common extranodal sites outside the CNS were renal/adrenal (n=6, 12%), paraspinal (n=5, 10%), and testicular (n=4, 8%). The majority of R-CHOP cycles (89%, n=222) included MTX with a median number of MTX-containing R-CHOP cycles administered per patient of 5 (range, 1-6). MTX starting dose was 3.5 g/m 2 in all but 3 patients (range, 1.5 - 2 g/m 2). Intrathecal MTX was administered in 21 patients (42%). Treatment with RM-CHOP was followed by consolidative stem cell transplantation in 15 patients (30%) including 14 autologous (28%) and 1 (2%) allogeneic. The objective response rate following RM-CHOP was 66% including complete response in 60%. With a median follow-up of 31 months (range, 4 - 100), the median PFS and OS were 17.7 months (95% confidence interval (CI), 6.9 - not reached [NR]) and NR (95% CI, 12.5 - NR), respectively, with 1-year PFS and OS of 57% (95% CI, 42-69%) and 68% (95% CI, 52-79%), respectively (Figure A). Twelve patients had CNS relapse/progression with a 1-year cumulative incidence of CNS progression/relapse of 21% (95% CI, 10-33%) (Figure B). Outcomes were particularly poor in patients with HGBCL, with median PFS and OS of 6.3 (95%CI, 1.2 - 9.8) months and 7.3 (95%CI, 1.2 - 21.2) months, and 1-year PFS and OS of 13% (95%CI, 1-44%) and 38% (95% CI, 9-68%), respectively (Figures C and D). Of the 7 patients with HGBCL who relapsed/progressed, 3 had CNS involvement only (1 parenchymal, 2 leptomeningeal), 3 had systemic involvement only, and 1 had both (parenchymal). Three patients received subsequent systemic treatment and only 1 responded (partial response). In patients with DLBCL, with a median follow-up of 33.5 months (range, 4 - 100), the median PFS and OS were both NR (95%CI, 9.5 months - NR and 21 months - NR, respectively) and the 1-year PFS and OS were 65% (95% CI, 49-78%) and 74% (95%CI, 57-85%), respectively. Of the 14 patients with DLBCL who relapsed/progressed, 8 had CNS involvement only (4 parenchymal, 2 leptomeningeal, 2 both) and 6 had systemic involvement only. Nine patients received subsequent systemic treatment of whom 5 patients responded (3 complete and 2 partial responses) Conclusions. To our knowledge, this is one of the largest studies of patients with DLBCL and HGBCL with synchronous CNS and systemic involvement at diagnosis treated with RM-CHOP. Patients with HGBCL had poor outcomes with median PFS and OS of 6 and 7 months, respectively. Patients with DLBCL had more favorable outcomes with median PFS and OS not reached after a median follow-up of 33.5 months. CNS involvement was more common than isolated systemic involvement at relapse/progression. CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis remains a major therapeutic challenge, dictates clinical outcomes, and requires more effective treatment options. Figure 1 Figure 1. Disclosures Dotson: AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Bond: Kite/Gilead: Honoraria. Epperla: Genzyme: Honoraria; Karyopharm: Other: Ad Board; Beigene: Speakers Bureau; Verastem: Speakers Bureau. Christian: Millenium: Other: Institution: Research Grant/Funding; Triphase: Other: Institution: Research Grant/Funding; Celgene/BMS: Other: Institution: Research Grant/Funding; Acerta: Other: Institution: Research Grant/Funding; Seattle Genetics: Consultancy, Other: Institution: Research Grant/Funding; Genentech: Consultancy, Other: Institution: Research Grant/Funding; AstraZeneca: Consultancy; VeraStem: Consultancy; Morphosys: Consultancy, Other: Institution: Research Grant/Funding; Immunomedics: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding. Baiocchi: Prelude Therapeutics: Consultancy; Atara Biotherapeutics: Consultancy; Codiak Biosciences: Research Funding; viracta: Consultancy, Current holder of stock options in a privately-held company. Maddocks: Karyopharm: Divested equity in a private or publicly-traded company in the past 24 months; Morphosys: Divested equity in a private or publicly-traded company in the past 24 months; ADC Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Beigene: Divested equity in a private or publicly-traded company in the past 24 months; KITE: Divested equity in a private or publicly-traded company in the past 24 months; Celgene: Divested equity in a private or publicly-traded company in the past 24 months; Pharmacyclics: Divested equity in a private or publicly-traded company in the past 24 months; BMS: Divested equity in a private or publicly-traded company in the past 24 months; Merck: Divested equity in a private or publicly-traded company in the past 24 months; Novatis: Divested equity in a private or publicly-traded company in the past 24 months; Janssen: Divested equity in a private or publicly-traded company in the past 24 months; Seattle Genetics: Divested equity in a private or publicly-traded company in the past 24 months. Sawalha: Epizyme: Consultancy; BeiGene: Research Funding; Celgene/BMS: Research Funding; TG Therapeutics: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-148662

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4185-4185

Abstract: B-cell activating factor (BAFF) belongs to the TNF ligand superfamily of cytokines involved in B cell survival and maturation. BAFF is produced by diverse cell types including innate immune cells like monocytes and dendritic cells as well as T cells, activated B cells, and bone marrow stromal cells. BAFF binds to the BAFF receptor (BAFF-R) with high affinity compared to the other BAFF receptors, BCMA and TACI. While BAFF is known to regulate normal B-cell development and proliferation, it also contributes to survival in chronic lymphocytic leukemia (CLL). We observed expression of BAFF-R on virtually all B cells from CLL patients. B-CLL cells have strong up-regulation of BAFF and BAFF-R compared to normal healthy B cells. We describe here the in-vitro and in-vivo evaluation in CLL of B-1239, a fully human anti-BAFF-R monoclonal IgG1 antibody. B-1239 is devoid of fucose residues in its Fc domain, resulting in enhanced binding to FCgammaRIIIa activating receptor on Natural Killer (NK) cells. While B-1239 failed to induce direct or complement mediated cytotoxicity, binding of B-1239 to CLL cells resulted in enhanced antibody dependent cellular cytotoxicity (ADCC) with allogeneic or autologous NK effector cells in-vitro. Indeed, at a therapeutically relevant concentration of 10 ug/mL B-1239 shows more than 30% increased relative cytotoxic activity over current CLL antibody therapeutic Rituximab. Dilutions of B-1239 down to 0.01 ug/mL showed similar cytotoxicity to the 10 ug/mL concentration. At 0.0001 ug/mL B-1239 has a 40% cytotoxic effect on CLL cells in ADCC assays while antibody therapeutic controls, like Rituximab, show virtually no cytotoxic activity. Furthermore, B-1239 mediated antibody-dependent cellular phagocytosis (ADCP) by monocyte-derived macrophages and mediated activation of monocytes and macrophages as detected by TNF-alpha production. Consistent with the cross reactivity to murine BAFF-R, flow cytometric analysis revealed binding of B-1239 to CD5+CD19+ leukemic B cells from Eu-Tcl-1 transgenic mouse CLL cells. A single dose of B-1239 by i.v injection into Eu-Tcl-1 mice resulted in dramatic reduction in circulating CD5+CD19+ leukemic B cells in all three B-1239 injected mice. In contrast, we observed continued increase of leukemic CD5+CD19+ populations in the two vehicle treated mice. Ongoing studies are focused on determining how targeting BAFF-R on CLL B-cells depletes the leukemic population both in-vitro and in-vivo and the downstream effects of targeting through this receptor. Collectively, these results demonstrate that targeting BAFF-R on CLL cells provides a B-cell specific approach for rapid and robust depletion of leukemic CLL cells and provides evidence for a strong therapeutic advantage in BAFF-R targeted therapies in CLL. Disclosures: Huet: Novartis: Employment, Employment Related Perks Other. Gram:Novartis: Employment, Employment Related Perks Other. Baeck:Novartis: Employment, Employment Related Perks Other.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.4185.4185

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3982-3982

Abstract: Background: Follicular lymphoma (FL) is the most common indolent lymphoma and is generally characterized by prolonged survival with multiple relapses throughout the disease course. There is no standard of care as to the initial choice or sequencing of treatments for relapsed disease. Novel agents approved in the relapsed setting include lenalidomide in combination with rituximab (R2) and PI3K inhibitors (PI3Ki) including idelalisib, duvelisib, and copanlisib. However, there are no prospective data comparing the safety/efficacy of these novel agents to guide treatment selection. We aimed to examine the characteristics and outcomes of patients with relapsed follicular lymphoma treated with these novel agents. Methods: We conducted a retrospective analysis of adult patients with FL treated with commercially-available novel agents at 10 US academic cancer centers. Patients were excluded if they received one of these therapies as first line therapy or for the treatment of transformed disease. Treatment with lenalidomide or PI3Ki was determined by the treating physician, as was the decision to incorporate monoclonal antibody (mAb). For patients who received both classes of novel agent, baseline and treatment characteristics were grouped by first novel class used. The Fisher's Exact test was used to compare categorical variables and the Mann Whitney U test for continuous variables. Progression-free survival (PFS) was defined as time from the initiation of the first novel agent to progression of disease (POD), either FL or transformed disease, or death from any cause. Overall survival (OS) was defined as time from the initiation of the first novel agent to death from any cause. Outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: 98 patients were included. Available baseline characteristics at diagnosis are described in Table 1. The median time from the end of the last FL treatment to the start of the first novel agent was 12 months (range 0-79). The first novel agent was lenalidomide +/-mAb in 49% (n=48) of the patients and a PI3Ki +/- mAb in 51% (n=50) of patients. Idelalisib was the most commonly used PI3Ki (n=47) followed by copanlisib (n=2) and duvelisib (n=1). The median number of therapies prior to the first novel agent was 2 (range 1-8) and not significantly different between treatment classes. Reason for discontinuation of novel agent was significantly different between groups with greater discontinuations due to toxicity (40% vs 28%) and transformed disease (15% vs. 3%) for the PI3Ki ± mAb group vs. lenalidomide ± mAb group, respectively (p = 0.02). The median PFS and OS for the entire cohort was 10 months (95% CI 7.6-14) and 120 months (95% CI, 49-NA), respectively (Figure A). When comparing outcomes to current FDA approvals-lenalidomide + mAb (n=43) versus PI3Ki monotherapy (PI3Ki, n=38), the median PFS was significantly longer in the lenalidamide + mAb group compared to the PI3Ki group (15 vs. 6 months, p=0.016), as was the OS (120 vs. 37 months, p=0.002, respectively, Figure B). Conclusions: In this multi-center analysis, despite multiple relapses, the median survival for FL patients treated with novel agents was 120 months from the initiation of the first novel therapy. With the caveat of retrospective comparison, lenalidomide + mAb (i.e. R2) appears superior to PI3Ki as first novel agent in the relapsed setting with the recognition that a high proportion of patients discontinued PI3Ki due to toxicity. Because the majority of the patients received idelalisib conclusions cannot be drawn about alternative PI3Ki which may have lower toxicity profiles or intermittent dosing strategies, allowing for safer and more prolonged treatment. Future prospective studies are needed to directly compare these agents and determine optimal sequencing of therapies. Disclosures Landsburg: Takeda: Research Funding; Triphase: Research Funding; Triphase: Research Funding; Takeda: Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kahl:AbbVie Inc, Acerta Pharma - A member of the AstraZeneca Group, AstraZeneca Pharmaceuticals LP, BeiGene, Celgene Corporation, Genentech, Pharmacyclics LLC, an AbbVie Company, Roche Laboratories Inc.: Consultancy. Maddocks:Merck: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Novartis: Research Funding. Danilov:TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; Bristol-Meyers Squibb: Research Funding; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding. Ujjani:Pharmacyclics: Honoraria; PCYC: Research Funding; Atara: Consultancy; Atara: Consultancy; Genentech: Honoraria; AbbVie: Honoraria, Research Funding; Gilead: Consultancy; Pharmacyclics: Honoraria; PCYC: Research Funding; Astrazeneca: Consultancy; Genentech: Honoraria; AbbVie: Honoraria, Research Funding. Lynch:Juno Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; T.G. Therapeutics: Research Funding; Incyte Corporation: Research Funding; Takeda Pharmaceuticals: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Nastoupil:Gilead: Honoraria; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Spectrum: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding. Ghosh:Forty Seven Inc: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Genentech: Research Funding; T G Therapeutics: Consultancy, Research Funding; Gilead/Kite: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Spectrum: Consultancy, Speakers Bureau; Astra Zeneca: Speakers Bureau. Stephens:Karyopharm: Research Funding; Gilead: Research Funding; Acerta: Research Funding. Cohen:ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Astra Zeneca: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy. Hill:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Takeda: Research Funding; Genentech: Consultancy, Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; TG therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-124783

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4387-4387

Abstract: Background: Ibrutinib, an orally bioavailable small molecular inhibitor of Bruton's tyrosine kinase (BTK), is an approved therapy for chronic lymphocytic leukemia (CLL), relapsed mantle cell lymphoma (MCL) and Waldenstrӧm's macroglobulinemia (WM). Beyond B lymphocytes, BTK signaling is important for collagen-mediated platelet activation, and BTK inhibition has been associated with primary hemostatic bleeding events (Levade et al Blood 2014). Although serious bleeding events have been uncommon (1-5%) in clinical trial populations, there is limited data describing the potential for increased serious bleeding incidence when ibrutinib is co-administered with other agents affecting the clotting cascade or platelet function. Methods: We conducted a retrospective cohort study to evaluate the incidence of major bleeding in patients receiving ibrutinib concomitantly with antiplatelet agents (non-steroidal anti-inflammatory agents, ADP inhibitors), anticoagulants (heparins, warfarin, novel oral anticoagulants), or supplements with potential anticoagulant activity (vitamin E and fish oil). Major bleeding events were identified using criteria developed by the International Society on Thrombosis and Haemostasis (Schulman et al J Thromb Haemost 2005). Patients 18-89 years of age and treated with ibrutinib for CLL, MCL, or WM between March 1, 2010 and March 1, 2015 were included. The primary endpoint of this study was the incidence of major bleeding events, but we also sought to identify risk factors associated with the development of major bleeding, focusing on potential drug interactions. Based on the historic prevalence of major bleeding in ibrutinib clinical studies, we calculated that at least 20 major bleeding events would need to be identified in order to perform blinded multinomial regression on the collected data of an estimated 400 patients. Results: 437 eligible patients were included in the analysis. Patients were overwhelmingly male (71.4%) and white (94.8%), with a mean age of 67.1 years (range: 29-89). 53.1% received ibrutinib as participants of a clinical trial, and the remainder received standard-of-care ibrutinib treatment. The table (upper panel) summarizes use of concomitant antihemostatic agents by presence or absence of major bleeding events. Characteristics of the major bleeding events are further detailed in the lower panel. The most commonly observed concomitant antihemostatic medication was aspirin, with 147 patients (33.6%) being exposed to aspirin within the study period. Fourteen instances of major bleeding were observed, corresponding to an overall incidence of 3.2%. These major bleeding events all occurred in CLL patients receiving ibrutinib at the standard dose of 420 mg daily. Two patients had platelet counts less than 50 k/µL at time of the bleeding event. One-half of the major bleeding events were observed in the absence of an antihemostatic medication, and 2 of the observed major bleeding events resulted in death (1 received concomitant warfarin). Fourteen patients (3.3%) in the group without major bleeding were on anticoagulation, 4 being warfarin. The most common sites of major bleeding were gastrointestinal (50%), intracranial (14.3%) and thoracic (14.3%). While most patients developing major bleeding permanently discontinued ibrutinib (57.1%), approximately one third of the patients who developed major bleeding subsequently resumed ibrutinib following resolution of the bleeding event. Subsequently, these patients did not experience a recurrent major bleeding event. The rate of major bleeding did not meet power to detect statistical differences in bleeding events when comparing concomitant therapy, Conclusions: Our observed incidence of major bleeding is consistent with previous controlled clinical trials, suggesting similar safety profile when ibrutinib is used outside of a controlled setting. Major bleeding events were uncommon despite the frequent co-administration of antiplatelet agents. However, because we modified practice early to avoid therapeutic anticoagulation during ibrutinib therapy whenever possible, the number of patients receiving such drugs in combination was small and precludes inferences regarding safety. Table Table. Disclosures Blum: Pharmacyclics: Research Funding. Awan:Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Woyach:Acerta: Research Funding; Karyopharm: Research Funding; Morphosys: Research Funding. Christian:Pharmacyclics: Research Funding; Janssen: Research Funding. Jones:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.4387.4387

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Therapeutic Advances in Hematology, SAGE Publications, Vol. 13 ( 2022-01), p. 204062072211129-

Abstract: The optimal treatment of patients with systemic diffuse large B-cell (DLBCL) or high-grade B-cell (HGBL) lymphomas with synchronous central nervous system (CNS) involvement at diagnosis is not well defined. High-dose methotrexate administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited. Objective: To report our experience with RM-CHOP in patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis. Design: A single-center retrospective analysis. Methods: We identified consecutive patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis who were treated with RM-CHOP from January 2012 to January 2021. Results: Fifty patients were included with a median age of 62 years; 82% had DLBCL ( n = 41) and 18% had HGBL ( n = 9). Treatment with RM-CHOP was followed by consolidative autologous hematopoietic cell transplantation in 14 patients (28%). The complete response (CR) rate following RM-CHOP was 62%. With a median follow-up of 40 months, the median progression-free (PFS) and overall (OS) survivals were 16 and 58 months, and the 2-year PFS and OS were 41% and 57%, respectively. The 2-year cumulative incidence of CNS progression/relapse was 29%. Outcomes were particularly poor in HGBL, with median PFS and OS of 6 and 7 months, compared with median PFS and OS of 22 months and not reached in DLBCL, respectively. The outcomes of patients with relapsed/progressive disease were poor, with only 63% of patients receiving subsequent treatments and only 21% achieving CR to next subsequent treatment. Most patients (58%) with disease relapse/progression had CNS involvement which was associated with very poor outcomes (median OS of 2 months). Conclusion: CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis dictates clinical outcomes and requires more effective treatment options.

Type of Medium: Online Resource

ISSN: 2040-6207 , 2040-6215

URL: Article

DOI: 10.1177/20406207221112900

Language: English

Publisher: SAGE Publications

Publication Date: 2022

detail.hit.zdb_id: 2585183-4

In: Canadian Public Policy, Project MUSE, Vol. 36, No. 1 ( 2010), p. 133-135

Type of Medium: Online Resource

ISSN: 1911-9917

URL: Article

DOI: 10.1353/cpp.0.0049

Language: English

Publisher: Project MUSE

Publication Date: 2010

detail.hit.zdb_id: 2068300-5