Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3725-3725

Abstract: Background: Venetoclax (VEN), an oral B-cell lymphoma 2 inhibitor, is approved for use in adult patients (pts) with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). As a targeted and highly active antitumor agent, VEN induces rapid and profound tumor reduction. Inpatient monitoring for initial doses of VEN is recommended by US Prescribing Information for pts with medium tumor burden and reduced renal function or high tumor burden. Administration of debulking agents, such as obinutuzumab (G), help reduce tumor burden and, consequently, facilitate subsequent administration of VEN in the outpatient setting. However, tumor reduction data are needed to definitively establish the utility of a debulking strategy. This study performed disease restaging after every 2 cycles of debulking to evaluate the safety and efficacy of G ± bendamustine (B) as a debulking regimen before VEN treatment in the outpatient community setting. The safety and efficacy of subsequent VEN+G treatment after debulking was also evaluated. Methods: This open-label, Phase 3b study (NCT03406156) enrolled adult pts with previously untreated CLL/SLL (except those with 17p deletion) who had medium (any lymph node [LN] 5 to & lt;10 cm or absolute lymphocyte count [ALC] ≥25×10 9/L) or high (any LN ≥10 cm or any LN ≥5 cm and ALC ≥25×10 9/L) tumor burden. A maximum of six 28-day cycles of G±B were administered, and disease restaging was performed after every 2 cycles. Once low tumor burden was achieved (all LN & lt;5 cm and ALC & lt;25x10 9/L), VEN+G was administered for 5 cycles followed by VEN monotherapy for a total time on VEN of up to 1 year. Disease assessments were performed at the end of combination therapy (EoCT; 5 mo after last dose of G) and at the end of therapy (EoT; 3 mo after last dose of VEN), and peripheral blood was collected for assessment of minimal residual disease (MRD) using the clonoSEQ assay (Adaptive Biotechnologies). Undetectable MRD was defined as & lt;1 CLL cell/10 4 leukocytes ( & lt;10 -4; uMRD4), & lt;10 -5 (uMRD5), or & lt;10 -6 (uMRD6). The primary endpoints were the percentage of pts achieving low tumor burden after 2, 4, and 6 cycles of G±B debulking and complete remission (CR) and CR with incomplete marrow recovery (CRi) rates among pts receiving VEN. Results: Of 120 pts treated, 81 received G for debulking and 39 received G+B. As of 13 May 2021, 2 pts remained on study treatment, 108 were in posttreatment follow-up, and 10 had discontinued the study for reasons including death (n=7), withdrawn consent (n=2), and COVID-19 infection (n=1). At baseline, 82.5% of pts had ALC ≥25x10 9/L, 33.3% had LN ≥5 cm, and 24.2%/75.0%/0.8% had high/medium/low tumor burden, respectively. Low tumor burden was achieved in 91.6% (109/119) of evaluable pts receiving G±B debulking. In the all-treated population (N=120), the objective response rate (ORR) was 90.0% and the CR/CRi rate was 35.8%. Among pts receiving VEN with disease assessment at EoT (N=76), the ORR was 98.7% and the CR/CRi rate was 44.7% (Table). The best uMRD4 rates in peripheral blood were 89.2% (107/120) for all-treated and 98.2% (107/109) for evaluable pts. Among evaluable pts, the uMRD4 rates were 100% (100/100) and 97.1% (68/70) at EoCT and EoT, respectively. Among pts with MRD assessments at both timepoints (N=67), 19.4% had a deepening of their MRD response from EoCT to EoT, and 67.2% maintained the same MRD level (Figure). At a median follow-up of 24.0 mo, 7 deaths (6 related to COVID-19 infection and 1 from cardiac complication after pancreatic mass resection) and no incidences of disease progression were reported; the estimated 18-mo PFS was 94.1%. In pts treated with G vs G+B debulking, respectively, the incidences of Grade ≥3 TEAEs were 71.6% vs 84.6% (most common was neutropenia at 28.4% vs 41.0%) and serious AEs were 23.5% vs 17.9% (most common were pneumonia and COVID-19 pneumonia, each at 3.7% vs 2.6%). Conclusion: In this study, most (91.6%) pts achieved low tumor burden after debulking. The uMRD4 rate was 98.2% among MRD-evaluable pts (89.2% among all pts), with 100% and 97.1% uMRD4 rates at EoCT and EoT, respectively. Overall, these results highlight the utility of G±B as an effective debulking strategy that can facilitate VEN treatment initiation in the outpatient setting. The efficacy and safety results are consistent with other VEN+G trials. Preventive measures for COVID-19 should be continuously emphasized for pts with CLL. Figure 1 Figure 1. Disclosures Flinn: AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Andorsky: AbbVie: Research Funding; Celgene/Bristol Myers Squibb: Consultancy; Celgene/Bristol Myers Squibb: Research Funding; Epizyme: Research Funding; AstraZeneca: Other: served on steering committees; AbbVie: Consultancy. Melear: TG Therapeutics: Speakers Bureau; Astrazeneca: Speakers Bureau; Janssen: Speakers Bureau. Manda: Morphosys: Honoraria; Genmab: Current equity holder in publicly-traded company. Kolibaba: TG Therapeutics: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Atara Biotechm: Consultancy; McKesson Specialty Health: Consultancy; Sunitomo Dainippon Pharma: Consultancy; Tolero Pharma: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Yimer: GSK: Speakers Bureau; Beigene: Speakers Bureau; Janssen: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Pharmacyclics: Speakers Bureau; Texas Oncology: Current Employment. Burke: Kura: Consultancy; Epizyme: Consultancy; Kymera: Consultancy; Adaptive Biotechnologies: Consultancy; Roche/Genentech: Consultancy; Beigene: Consultancy, Speakers Bureau; MorphoSys: Consultancy; Verastem: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; SeaGen: Consultancy, Speakers Bureau. Fanning: BMS: Speakers Bureau; TG Pharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genmab: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Speakers Bureau; Takeda: Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees. Islas-Ohlmayer: OHC/USON: Current Employment; AbbVie: Honoraria; Rigel: Honoraria, Speakers Bureau. Vizkelety: AbbVie: Current Employment, Current equity holder in publicly-traded company. Pesko: AbbVie: Current Employment, Current equity holder in publicly-traded company. Chyla: AbbVie: Current Employment, Current equity holder in publicly-traded company. Jiang: AbbVie: Current Employment, Current equity holder in publicly-traded company. Sharman: Pharmacyclics LLC, an AbbVie Company: Consultancy; BMS: Consultancy; Lilly: Consultancy; BeiGene: Consultancy; Centessa: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; TG Therapeutics: Consultancy; AbbVie: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-147258

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. 134, No. Supplement_1 ( 2019-11-13), p. 3042-3042

Abstract: BACKGROUND: Venetoclax is an effective oral agent for frontline treatment of patients with chronic lymphocytic leukemia (CLL). Due to the rapid induction of cell death caused by the targeted activity of venetoclax, some patients require inpatient monitoring for tumor lysis syndrome (TLS) at initiation of therapy. In the recent CLL14 study, 64% and 22% of venetoclax-treated patients were medium and high risk for TLS, respectively. This study used disease re-staging every two cycles to explore the efficacy of using of obinutuzumab, with or without bendamustine prior to initiation of venetoclax, to reduce tumor burden and thus eliminate the need for hospitalizations, as well as reduce the risk for TLS at the initiation of venetoclax therapy. METHODS: This is a single arm open-label, phase 3b trial (NCT03406156). Patients had previously untreated CLL/SLL (excluding those with 17p deletion), an Eastern Cooperative Oncology Group (ECOG) performance score of ≤1, and a medium (any lymph node 5 - 〈 10 cm or absolute lymphocyte count [ALC] ≥25 × 109 /L) or high (any lymph node ≥10 cm or ALC ≥25 × 109 /L and any lymph node ≥5 cm) tumor burden. Patients had tumor debulking (with obinutuzumab or obinutuzumab plus bendamustine) for a maximum of six 28-day cycles until low tumor burden (ALC 〈 25 × 109 /L and all lymph nodes 〈 5 cm) was achieved, at which point treatment with venetoclax plus obinutuzumab was initiated. The primary endpoints of the study were (1) the percentage of patients achieving low tumor burden after 2, 4, and 6 cycles of obinutuzumab, with or without bendamustine; and (2) the response rates of patients treated with venetoclax. RESULTS: A majority of patients were 〈 75 years old (87%, 60/69) with ALC ≥25 × 109 /L (81%, 56/69), medium TLS risk (81%, 56/69), and RAI stage 1/2 (52%, 36/69; 32% had RAI stage 3/4). Of 69 patients treated, 50 had debulking with obinutuzumab alone, and 19 with added bendamustine (11% [2/19] added bendamustine at cycle 3+); 51 patients completed debulking and 18 are ongoing. After two cycles of debulking, 77% (40/52) of evaluable patients achieved low tumor burden; after four cycles, 94% (45/48); and after six cycles, 98% (46/47) [Figure] . ALC was reduced to less than 25 × 109 /L in 98% (50/51) of evaluable patients after two cycles of obinutuzumab, without (100%; 43/43) or with bendamustine (7/8). Amongst those that received obintuzumab alone, 4 of 5 evaluable patients with lymph nodes 5-10 cm were debulked to 〈 5 cm by 4 cycles of therapy. For patients started with obinutuzumab plus bendamustine, all 4 evaluable patients with lymph nodes 5-10 cm were debulked to 〈 5 cm within 2 cycles, and 3 of 4 evaluable patients with nodes 〉 10 cm were debulked to 〈 5 cm by 4 cycles of therapy. Safety signals were consistent with the known profiles of bendamustine, obinutuzumab and venetoclax; the most frequently reported any-grade AEs ( 〉 30%) were infusion-related reactions (71%; all grade 1-2), nausea (39%), headache (35%) and fatigue (32%). Neutropenia (28%) and thrombocytopenia (10%) were the most frequently reported Grade 3+ AEs. AEs of TLS were reported in the debulking phase in 7% (5/69) of patients. A retrospective analysis using Howard criteria for TLS identified three additional patients with laboratory TLS: two occurred during the debulking phase and one during the venetoclax phase, all driven by phosphate and uric acid. Uric acid levels were below the institutional upper limit of normal for the patient with TLS during venetoclax treatment and did not require management. No patients were hospitalized during venetoclax ramp up. CONCLUSIONS: Two cycles of obinutuzumab prior to initiation of venetoclax was an effective debulking strategy for patients with ALC 〉 25 × 109 /L and lymph nodes 〈 5 cm, with over 98% success rate; the addition of bendamustine increased effective debulking for patients with nodes 5-10 cm. Patients with nodes 〉 5 cm treated with obinutuzumab or 〉 10 cm treated with obinutuzumab plus bendamustine may need 〉 2 cycles to achieve low tumor burden. Debulking via obinutuzumab, with or without bendamustine, may allow more patients to be administered venetoclax in the outpatient setting, eliminating the need for hospitalization during venetoclax initiation. Figure Disclosures Sharman: AstraZeneca: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Andorsky:Genetech: Research Funding; Gilead: Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy; CTI: Research Funding. Melear:Texas Oncology: Employment; DARA: Speakers Bureau. Kolibaba:Atara Bio: Consultancy; AbbVie, Acerta, Celgene, Genentech, Gilead, Janssen, Novartis, Pharmacyclics, Seattle Genetics, TG Therapeutics: Research Funding; Verastem: Honoraria. Yimer:Clovis Oncology: Equity Ownership; Celgene: Honoraria; Seattle Genetics: Honoraria; Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau; Amgen: Consultancy; Puma Biotechnology: Equity Ownership. Burke:Celgene: Consultancy; Roche/Genentech: Consultancy; Gilead: Consultancy. Fanning:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Masud:AbbVie: Employment, Other: Stock/stock options. Zimmerman:AbbVie: Employment, Other: stock or options. Nielsen:AbbVie: Employment, Other: and may hold stock or stock options. Vizkelety:AbbVie: Employment, Other: stock or options. Jiang:AbbVie: Employment, Other: stock or options. Flinn:AbbVie, Seattle Genetics, TG Therapeutics, Verastem: Consultancy; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-127408

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. 102, No. 9 ( 2003-11-01), p. 3302-3310

Abstract: Distinct human dendritic cell (DC) subsets differentially control immunity. Thus, insights into their in vivo functions are important to understand the launching and modulation of immune responses. We show that nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice engrafted with human CD34+ hematopoietic progenitors develop human myeloid and plasmacytoid DCs. The skin displays immature DCs expressing Langerin, while other tissues display interstitial DCs. Myeloid DCs from these mice induce proliferation of allogeneic CD4 T cells in vitro, and bone marrow human cells containing plasmacytoid DCs release interferon-α (IFN-α) upon influenza virus exposure. Injection of influenza virus into reconstituted mice triggers IFN-α release and maturation of mDCs. Thus, these mice may provide a model to study the pathophysiology of human DC subsets.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2003-02-0384

Language: English

Publisher: American Society of Hematology

Publication Date: 2003

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: British Journal of Haematology, Wiley, Vol. 189, No. 3 ( 2020-05)

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.v189.3

DOI: 10.1111/bjh.16499

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 1475751-5

In: STEM CELLS, Oxford University Press (OUP), Vol. 23, No. 2 ( 2005-02), p. 264-278

Type of Medium: Online Resource

ISSN: 1066-5099 , 1549-4918

URL: Article

DOI: 10.1634/stemcells.2004-0116

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2005

detail.hit.zdb_id: 2030643-X

detail.hit.zdb_id: 1143556-2

detail.hit.zdb_id: 605570-9

SSG: 12

In: American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Wiley, Vol. 184, No. 4 ( 2020-12), p. 1052-1059

Abstract: Multiple myeloma is the most common hematological malignancy in Gaucher disease type 1 (GD1). There is a lack of outcome data and consensus regarding screening of gammopathies. This study explores utility of screening in Porto Alegre, Brazil, and Cincinnati, Ohio. A retrospective analysis of clinical information and laboratory data from GD1 patients was performed. Over 19 years, 68 individuals with GD1 (31 males, 37 females) underwent screening, and 20 (29.4%) had abnormalities. Twelve (17.6%) had polyclonal gammopathy (mean age 24.2 years, p = .02), seven (10%) had monoclonal gammopathy of uncertain significance (MGUS; mean age 52.7 years, p = .009). One had multiple myeloma (age 61 years). Risk factors for MGUS included male gender ( p = .05), p.N409S allele ( p = .032). MGUS developed in six of 62 treated and two of four untreated individuals. Of those with MGUS receiving treatment, four were on enzyme replacement therapy (ERT) and one on substrate reduction therapy (SRT). Gammopathy normalized in 13 treated individuals (10 polyclonal, three MGUS) and remained abnormal in two treated individuals (two polyclonal, two MGUS). Gammopathy relapse was seen in one individual with MGUS and three with polyclonal gammopathy. This study describes screening for gammopathies and identifies risk factors in individuals with GD1.

Type of Medium: Online Resource

ISSN: 1552-4868 , 1552-4876

URL: Issue

URL: Article

DOI: 10.1002/ajmg.c.v184.4

DOI: 10.1002/ajmg.c.31870

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 2143867-5

SSG: 12

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 20 ( 2020-09), p. S219-S220

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(20)30787-4

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e5881312-

Type of Medium: Online Resource

ISSN: 2572-9241

URL: Article

DOI: 10.1097/01.HS9.0000971152.58813.12

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2023

detail.hit.zdb_id: 2922183-3

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2277-2277

Abstract: Abstract 2277 Poster Board II-254 Background: Plerixafor plus G-CSF has been shown to mobilize more CD34+ cells than G-CSF alone for autologous (auto) hematopoietic stem cell transplant (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34+ cells prior to HSCT. Comparing the effectiveness of CD34+ cell mobilization, cost, logistical issues, and clinical outcomes between plerixafor/G-CSF and chemotherapy/G-CSF mobilized pts may help better define optimal mobilization regimens. Patients and Methods: We performed a retrospective study of pts who participated in the expanded access program (EAP) of plerixafor/G-CSF for upfront mobilization of CD34+ cells, and compared the costs of mobilization and clinical outcomes to matched historical controls mobilized with chemotherapy/G-CSF at two centers that participated in the study. Control pts were matched for age, sex, disease stage, and number of prior therapies. Control pts received cyclophosphamide 3-5 gm/m2 followed by daily G-CSF. Study pts received G-CSF 10 mcg/kg daily for 5 days and plerixafor 0.24 mg/kg was given on the evening of day 4, twelve hours before a 3 blood volume apheresis on day 5, and the same plerixafor and G-CSF dosing was given for each subsequent day of apheresis. Apheresis was scheduled for 5 days after starting G-CSF in the study pts and 10 days after starting G-CSF in the control pts, but the actual start of apheresis was based on the peripheral blood (PB) CD34+ cell counts of 10/ul or greater. Mobilization costs were considered to be the costs of medical procedures, resource utilization and medications. Median national CMS national reimbursement rates were used to evaluate the costs of mobilization procedures, hospitalization, provider visits, apheresis, CD34+ cell processing and cryopreservation. Average sale price was used for medications related to mobilization including G-CSF, plerixafor, cyclophosphamide, mesna, antiemetics and antimicrobials. Results: A total of 34 patients from EAP and 34 matched controls were studied (Rocky Mountain BMT:25 study pts and 25 controls, Texas Transplant Institute:9 study pts and 9 controls). Study pts had a median age of 58 years, 18 (53%) were male, and had myeloma (n=20, 59%), or NHL (n=14, 41%). Control pts had a median age of 58 years, 18 (53%) were male and had myeloma (n=20, 59%), NHL (n=13, 38%), or Hodgkins disease (n=1, 3%). Comparison of the G-CSF dose, the number of doses of G-CSF, number of apheresis, total CD34+ cells collected, and cost is given in the table. All pts proceeded to auto HSCT with no difference in median time to ANC or platelet engraftment. The median costs of mobilization were similar between the groups. Two pts in the control group were hospitalized for neutropenic fever during the mobilization period after receiving cyclophosphamide. Apheresis started on the scheduled day in 27 (79%) of study pts and in 18 (53%) of control pts (p=0.021). Unplanned starts of apheresis resulted in 17 (50%) of control pts undergoing weekend apheresis. CMS national reimbursement data does not differentiate the costs of weekend or weekday apheresis or flow cytometry, and thus no cost difference for weekend procedures is reflected in the cost data. Study pts received a median of 1 dose of plerixafor (median 16.9 mg), and the average sale price for plerixafor in this analysis was set at $6,250 per 24 mg/vial. Adding this cost to the study pts resulted in a non-significant difference in total cost of mobilization for the two groups. Conclusion: In conclusion, plerixafor/G-CSF compared to cyclophosphamide/G-CSF for upfront mobilization of CD34+ cells for auto HSCT results in similar number of cells collected, cost of mobilization, and clinical outcomes. However, plerixafor/G-CSF mobilization resulted in more predictable days of collection, no weekend apheresis procedures, and no unscheduled hospital admissions. Higher acquisition cost of plerixafor was offset by less G-CSF use and less resource utilization compared to cyclophosphamide based mobilization. Disclosures: Shaughnessy: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Silva:Genzyme: Consultancy. Steinberg:Genzyme: Consultancy. Selvey:Genzyme: Consultancy. Maris:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. McSweeney:Genzyme: Honoraria, 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.V114.22.2277.2277

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

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. 527-527

Abstract: Background: Patients with relapsed or refractory (R/R) DLBCL generally have a poor prognosis, particularly if they are not candidates for autologous stem cell transplantation (ASCT) or experience relapse following approved CAR-T therapies. The UNITY-NHL study systematically explored the efficacy and tolerability of the PI3K-d/CK1-e inhibitor, umbralisib, alone (umbra), and in combination with the glycoengineered anti-CD20 monoclonal antibody ublituximab (U2), followed by a cohort treated with U2 plus bendamustine (U2+benda). Herein we report on the experience in a large cohort of patients with R/R DLBCL. Methods: This study explored a sequential combination design as described above. Eligible patients had histologically confirmed R/R DLBCL and were ineligible for ASCT, with no limit on number or type of prior treatment. Umbra was given orally at 800 mg once daily in 28-day cycles (C) until disease progression or unacceptable tolerability. Ublituximab was administered intravenously (IV) on Days 1, 8, and 15 of C1, on Day 1 of C2-6, and on Day 1 every 3C through C24. Benda was administered IV (90 mg/m 2) on Days 1/2 of C1-6. Cell of origin, NGS, and c-myc (FISH) were analyzed centrally. The primary endpoint of the study was overall response rate (ORR) as assessed by an independent review committee. Secondary endpoints included duration of response, progression-free survival, time to response, and safety. Results: 226 patients with DLBCL were enrolled as follows: umbra monotherapy (n=30), U2 (n=66), and U2+benda (n=130). The population demographics included the following features: median age was 72 years (range 32-95); 59% were male; 64% of patients had stage III or IV disease; 58% were refractory to their immediate prior therapy; and the median number of prior therapies was 2 (range 1-8). There were no substantive differences in these characteristics across cohorts. Median follow-up for the umbra, U2, and U2+benda arms was 51 months (range 47-61), 46 months (range 41-57), and 40 months (range 35-47), respectively. Overall and complete response rates for the umbra mono, U2, and U2+benda arms were 13.3% (CR 3.3%), 31.8% (CR 10.6%), and 43.1% (CR 16.9%), respectively. Results pertaining to secondary endpoints are listed in Table 1. Correlation of response to cell of origin and mutation/c-myc status is ongoing and will be available at the time of presentation. Adverse events (AEs) were similar across the cohorts, with the exception of hematologic AEs which were increased in patients receiving benda. The most common all-grade AEs by treatment arm (umbra, U2, and U2+benda, respectively) were diarrhea (47%; 41%; and 48%), nausea (40%; 45%; and 45%), fatigue (33%; 30%; and 41%) and neutropenia (3.3%; 18%; and 32%). All-grade AEs of special interest included non-infectious colitis (3.3%, 1.5%, and 2.3%) and pneumonitis (3%, 1.5%, and 1.5%) in umbra, U2 and U2+benda treated patients respectively. Grade 3/4 AEs were uncommon, with the only events & gt;10% being limited to neutropenia (11% for U2; 27% for U2+benda), and anemia (17% for U2+benda). Conclusions: In the DLBCL cohort of UNITY-NHL, the U2+benda triplet regimen was active and well tolerated in patients with R/R DLBCL who were unsuitable for transplant or who had relapsed following ASCT. Umbra monotherapy and U2 were also well tolerated but resulted in lower ORR than in the U2+benda cohort. Figure 1 Figure 1. Disclosures Burke: X4 Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; SeaGen: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; Roche/Genentech: Consultancy; Epizyme: Consultancy; Adaptive Biotechnologies: Consultancy; Kura: Consultancy; MorphoSys: Consultancy; AstraZeneca: Consultancy; Kymera: Consultancy; AbbVie: Consultancy; Verastem: Consultancy. Fonseca: Amgen: Honoraria, Speakers Bureau; Celgene/BMS: Honoraria, Speakers Bureau; Dava Oncology: Honoraria; Epizyme: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria. Jurczak: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Morphosys: Research Funding; Mei Pharma: Research Funding; Merck: Research Funding; Loxo Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Epizyme: Research Funding; Debbiopharm: Research Funding; Celgene: Research Funding; Celtrion: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Melear: TG Therapeutics: Speakers Bureau; Astrazeneca: Speakers Bureau; Janssen: Speakers Bureau. Islas-Ohlmayer: Seagen Inc.: Research Funding. Reeves: Apollomics, Inc.: Research Funding; Tarveda Therapeutics: Research Funding; Ascentage Pharmaceuticals: Research Funding; Clovis Oncology: Research Funding; Arvinas: Research Funding; Pfizer: Research Funding; Ellipses: Research Funding; ImmunoGen: Research Funding; Karyopharm Therapeutics: Honoraria, Research Funding; Moderna: Research Funding; Thrive: Research Funding; Genentech: Research Funding; Incyte Corporation: Research Funding; Astellas Pharma: Research Funding; IDEAYA Biosciences: Research Funding; Pharmacyclics: Research Funding; Loxo Oncology: Research Funding; AbbVie Inc.: Research Funding; Celgene: Research Funding; GSK: Research Funding; Jiangsu Hengrui Medicine Co.: Research Funding; Arcus Biosciences: Research Funding; Calithera: Research Funding; Amgen: Research Funding; Mirati Therapeutics, Inc.: Research Funding; Array BioPharma Inc.: Research Funding; Taiho Pharmaceutical: Research Funding; Boehringer Ingelheim: Research Funding; GI Therapeutics Inc.: Research Funding; Hutchison: Research Funding; MacroGenics: Research Funding; Ipsen: Research Funding; MedImmune, LLC.: Research Funding; BeiGene: Research Funding; TG Therapeutics: Research Funding; Acerta Pharma: Research Funding; Verastem: Research Funding; Janssen Pharmaceuticals: Research Funding, Speakers Bureau; Eisai Co.: Research Funding, Speakers Bureau; Roche Pharma: Research Funding; Novartis Pharmaceuticals: Research Funding; Daiichi Sankyo: Research Funding; Arvinas: Research Funding; CytomX: Research Funding; Sermonix Pharmaceutical: Research Funding; Seattle Genetics: Research Funding; AstraZeneca: Research Funding; Evelo Biosciences: Research Funding. Wróbel: Takeda: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Honoraria; Roche: Honoraria, Research Funding, Speakers Bureau; BeiGene: Honoraria; Janssen: Honoraria, Speakers Bureau. Pagel: Incyte/MorphoSys: Consultancy; MEI Pharma: Consultancy; Pharmacyclics/AbbVie: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; Kite, a Gilead Company: Consultancy; Epizyme: Consultancy; BeiGene: Consultancy. Goldschmidt: Ontada: Current Employment; Blue Ridge Cancer Care: Current Employment; Amgen: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; TG Therapeutics: Honoraria; G1 Therapeutics: Honoraria, Speakers Bureau. Miskin: TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sportelli: TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. O'Connor: TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company; Nomocan: Consultancy; Dren: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Myeloid Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Kymera: Consultancy, Current equity holder in publicly-traded company; Mundipharma: Consultancy. Ghosh: Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Genmab: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Genentech: Research Funding; Karyopharma: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Adaptive Biotech: Consultancy, Honoraria; Epizyme: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-151054

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7