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In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 4, No. S1 ( 2016-11)

Type of Medium: Online Resource

ISSN: 2051-1426

URL: Article

DOI: 10.1186/s40425-016-0172-7

Language: English

Publisher: BMJ

Publication Date: 2016

detail.hit.zdb_id: 2719863-7

In: The Lancet Haematology, Elsevier BV, Vol. 6, No. 9 ( 2019-09), p. e459-e469

Type of Medium: Online Resource

ISSN: 2352-3026

URL: Article

DOI: 10.1016/S2352-3026(19)30110-3

Language: English

Publisher: Elsevier BV

Publication Date: 2019

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 19, No. 3 ( 2001-02-01), p. 742-749

Abstract: PURPOSE: To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL). PATIENTS AND METHODS: IC consisted of thiotepa 250 mg/m 2 /d days −9 through −7, busulfan 10 mg/kg (total dose) days −6 through −4, and cyclophosphamide 60 mg/kg/d days −3 and −2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m 2 /d days 2 through 5 and 50 mg/m 2 /d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m 2 /d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly. RESULTS: Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure. CONCLUSION: IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients ≥ 60 years. A prospective multicenter study is ongoing.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2001.19.3.742

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2001

detail.hit.zdb_id: 2005181-5

In: eClinicalMedicine, Elsevier BV, Vol. 62 ( 2023-08), p. 102131-

Type of Medium: Online Resource

ISSN: 2589-5370

URL: Article

DOI: 10.1016/j.eclinm.2023.102131

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2946413-4

In: American Journal of Hematology, Wiley, Vol. 98, No. 4 ( 2023-04), p. 645-657

Abstract: Advances in molecular profiling of newly diagnosed diffuse large B‐cell lymphoma (DLBCL) have recently refine genetic subgroups. Genetic subgroups remain undetermined at the time of relapse or refractory (RR) disease. This study aims to decipher genetic subgroups and search for prognostic molecular biomarkers in patients with RR‐DLBCL. From 2015 to 2021, targeted next‐generation sequencing analyses of germline‐matched tumor samples and fresh tissue from RR‐DLBCL patients were performed. Unsupervised clustering of somatic mutations was performed and correlations with patient outcome were sought. A number of 120 patients with RR‐DLBCL were included in LNH‐EP1 study and a molecular tumor landscape was successfully analyzed in 87% of patients (104/120 tumor samples). The median age was 67.5 years (range 27.4–87.4), median number of previous treatments was 2 (range 1–9). The most frequently mutated genes were TP53 ( n  = 53 mutations; 42% of samples), CREBBP ( n  = 39; 32%), BCL2 ( n  = 86; 31%), KMT2D ( n  = 39; 28%) and PIM1 ( n  = 54; 22%). Unsupervised clustering separated three genetic subgroups entitled BST (enriched in BCL2 , SOCS1 , and TNFRSF14 mutations); TKS (enriched in TP53 , KMT2D , and STAT6 mutations); and PCM (enriched in PIM1, CD79B , and MYD88 mutations). Median overall survival (OS) was 11.0 (95% confidence interval [CI]: 8.1–12.6) months. OS was not significantly different between the three genetic subgroups. GNA13 mutant was significantly associated with an increased risk of death (hazard ratio: 6.6 [95% CI: 2.1–20.6]; p  = .0011) and shorter OS ( p  = .0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v98.4

DOI: 10.1002/ajh.26835

Language: English

Publisher: Wiley

Publication Date: 2023

detail.hit.zdb_id: 1492749-4

In: SSRN Electronic Journal, Elsevier BV

Type of Medium: Online Resource

ISSN: 1556-5068

URL: Article

DOI: 10.2139/ssrn.4057122

Language: English

Publisher: Elsevier BV

Publication Date: 2022

In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 8_Supplement ( 2023-04-14), p. CT265-CT265

Abstract: Background: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory immune checkpoint receptor expressed on subsets of T-cells and natural killer (NK) cells. TIGIT inhibits T and NK cell function by binding to CD155 and CD112. SEA-TGT is an investigational human, nonfucosylated monoclonal antibody directed against TIGIT, blocking TIGIT's interaction with CD155 and CD112. SGNTGT-001 (NCT04254107) is a phase 1, open-label, multicenter study of SEA-TGT in patients (pts) with advanced malignancies (solid tumors and lymphomas). In this abstract, we present data from the dose-escalation phase (Part A). Methods: Pts received SEA-TGT ranging from 0.01 to 6.0 mg/kg of body weight intravenously every 3 weeks (Q3W). The primary objectives were to evaluate the safety and tolerability of SEA-TGT and identify the maximum tolerated dose (MTD) or the recommended dose and schedule of SEA-TGT. The optimal biological dose was defined using the Clinical Utility Index. Secondary objectives included the evaluation of antitumor activity, pharmacokinetics (PK) and immunogenicity. Antitumor activity was based on Response Evaluation Criteria in Solid Tumors version 1.1 or the Lugano classification criteria with Lymphoma Response to Immunomodulatory Therapy Criteria. Results: From June 12, 2020, to October 5, 2022, 41 pts were enrolled (2, 4, 5, 11, 12, and 7 pts in the 0.01, 0.1, 0.3, 1, 3, and 6 mg/kg cohorts, respectively). Among the 39 pts who were treated 23 pts had solid tumors and 16 had lymphomas. The median number of prior therapies across all cohorts was 5. Treatment emergent adverse events of any grade were reported in 100% of pts, and treatment-related adverse events (TRAEs) of any grade were reported in 69.2%. TRAEs seen in ≥10% of the pts were infusion-related reaction (38.5%), chills (25.6%), pyrexia (17.9%), fatigue (12.8%), maculopapular rash (12.8%), and rash (10.3%). Seven pts (17.9%) reported TRAEs grade ≥3, and rash (5.1%) was the most frequently reported. No grade 4 or 5 TRAEs were reported. One dose-limiting toxicity, pruritic rash, was observed in 1 pt in the 6 mg/kg cohort, and MTD was not exceeded. Based on the PK and pharmacodynamic data, 1 mg/kg Q3W was selected as the optimal biological dose for the expansion cohorts. One partial response was observed in a pt with gastric cancer, and 2 partial metabolic responses were seen in a pt with Hodgkin’s lymphoma and a pt with diffuse large B-cell lymphoma. Conclusions: Overall, clinical data for SEA-TGT from the SGNTGT-001 trial suggest a manageable and tolerable safety profile. Preliminary antitumor activity warrants further clinical evaluation of SEA-TGT. SGNTGT-001 is ongoing and evaluating monotherapy and combination therapies. Citation Format: Elena Garralda Cabanas, Elisa Fontana, Honey Kumar Oberoi, Nataliya V. Uboha, Ecaterina E. Dumbrava, Emiliano Calvo, Giuseppe Curigliano, Diwakar Davar, Bridget K. Keenan, Vincent K. Lam, Sudhir Manda, Amitkuma Mehta, Anna Minchom, Alison Moskowitz, Ravi Paluri, Vincent Ribrag, Donald Richards, Lillian Siu, Paul Swiecicki, Trisha Wise-Draper, Jasmine Zain, Andres Forero-Torres, Ping Xu, Stephen Ansell. Phase 1 dose-escalation study of SGN-TGT monotherapy in patients with advanced malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT265.

Type of Medium: Online Resource

ISSN: 1538-7445

URL: Article

DOI: 10.1158/1538-7445.AM2023-CT265

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2023

detail.hit.zdb_id: 2036785-5

detail.hit.zdb_id: 1432-1

detail.hit.zdb_id: 410466-3

In: European Journal of Cancer, Elsevier BV, Vol. 129 ( 2020-04), p. 71-79

Type of Medium: Online Resource

ISSN: 0959-8049

URL: Article

DOI: 10.1016/j.ejca.2020.01.013

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 1120460-6

detail.hit.zdb_id: 1468190-0

detail.hit.zdb_id: 82061-1

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2417-2417

Abstract: Background: Immunochemotherapy induction followed by rituximab maintenance is the standard of care in previously untreated symptomatic follicular lymphoma (FL). The phase 3 RELEVANCE study of chemotherapy-free combination immunotherapy with lenalidomide and rituximab (R 2) showed promising activity comparable to standard rituximab + chemotherapy (R-chemo) options (Morschhauser, F and Fowler, NH, et al. N Engl J Med. 2018). Reported here are the results of the second interim analysis. Methods: RELEVANCE is a global, randomized, phase 3 trial (NCT01650701) of R 2 vs R-chemo followed by rituximab in patients with previously untreated grade 1-3a FL requiring therapy according to GELF criteria. Lenalidomide dose was 20 mg/d, d2-22/28 for 6-12 cycles (c), continued in responders at 10 mg/d for a total of 18 c. Rituximab dose was 375 mg/m 2 weekly c1 and d1 c2-6 and continued in responders for 12 additional c (q8wk). R-chemo was given per investigator's choice of standard R + cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), R + bendamustine (R-B), or R-CVP, followed by 12 c of rituximab (q8wk). Co-primary endpoints were complete response (CR)/CR unconfirmed (CRu) at 120 wk and progression-free survival (PFS) by independent review committee (IRC) based on 1999 IWG criteria. The prespecified second interim analysis was done after 75% of total PFS events were reached. Results: 1030 patients with high tumor burden were randomized to R 2 (n = 513) and R-chemo (n = 517; 72% R-CHOP, 23% R-B, 5% R-CVP); baseline characteristics were similar in both groups. As of October 30, 2020, at median follow-up of 72 mo, 6-year PFS, according to IRC assessment using FDA censoring rules, was 60% for R 2 and 59% for R-chemo with a hazard ratio (HR) of 1.03 (95% CI, 0.84-1.27). Data according to investigator assessment and EMA censoring rules are shown in the table. Median PFS was not reached for both groups. CR/CRu rates at 120 wk by IRC was 48% for R 2 and 53% for R-chemo (P = 0.10). Secondary endpoints, including overall survival, event free survival, and time to next antilymphoma treatment, were also similar in both groups. 162 (32%) R 2 and 166 (32%) R-chemo patients experienced progression/relapse according to investigator assessment of which 107 and 99 patients received additional treatment(s), respectively. Histological transformation was documented in 13/513 patients the R 2 group and 11/517 patients in the R-chemo group over the 72 mo follow-up period. ORR and overall survival after subsequent treatment(s) for relapse/progression were similar in both groups. The overall safety profile in both groups was consistent with the 1st interim analysis. The number of patients with second primary malignancies (SPMs) were similar between both groups, occurring in 57 (11%) R 2-treated and 67 (13%) R-chemo-treated safety population patients. The total number of SPMs was 64 in the R 2 group and 87 in the R-chemo group, with invasive SPM accounting for 43 (67%) and 52 (60%), respectively. Grade 5 adverse events were reported in 9 (2%) R 2 and 6 (1%) R-chemo treated patients. Conclusions: R 2 continues to demonstrate comparable efficacy vs R-chemo in patients with previously untreated grade 1-3a FL requiring therapy with similar 6-year PFS (60% and 59%) and 6-year OS (89% in both groups). Also, response and overall survival after subsequent treatment were similar in both groups. The overall safety profile of both groups was consistent with the previous analysis, with no new safety signals detected. R 2 provides a chemo-free alternative to R-chemo based on immunotherapy/immunomodulation. Figure 1 Figure 1. Disclosures Morschhauser: Chugai: Honoraria; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Genentech, Inc.: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nastoupil: Bayer: Honoraria; Denovo Pharma: Other: DSMC; Gilead/Kite: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; MorphoSys: Honoraria; Caribou Biosciences: Research Funding; Genentech: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; IGM Biosciences: Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Epizyme: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding. Feugier: Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Palomba: Wolters Kluwer: Patents & Royalties; Lygenesis: Honoraria; Pluto: Honoraria; Ceramedix: Honoraria; Priothera: Honoraria; Nektar: Honoraria; Novartis: Consultancy; Seres: Honoraria, Other: Stock, Patents & Royalties, Research Funding; Rheos: Honoraria; Magenta: Honoraria; Juno: Patents & Royalties; BeiGene: Consultancy; Kite: Consultancy; WindMIL: Honoraria; Notch: Honoraria, Other: Stock; PCYC: Consultancy. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Libby: Genentech: Research Funding; Janssen: Consultancy, Research Funding; BMS: Research Funding; GSK: Research Funding. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Flinn: Infinity Pharmaceuticals: 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; Karyopharm Therapeutics: Other: All 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; Novartis: 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; TG Therapeutics: 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; BeiGene: Consultancy, Other: All consultancy and 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; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Kite, a Gilead Company: Consultancy, Other: All consultancy and 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; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; 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; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy and 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; Rhizen Pharmaceuticals: 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; Constellation Pharmaceuticals: Other: All 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; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and 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; Incyte: 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; Portola Pharmaceuticals: 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; Unum Therapeutics: 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; AbbVie: 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; AstraZeneca: 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; Calithera Biosciences: Other: All 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; Teva: Other: All 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; 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. Haioun: Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen-Cilag: Consultancy; Miltenyi Biotec: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead Sciences: Consultancy, Honoraria; Servier/Pfizer: Honoraria; Novartis: Honoraria. Ysebaert: Abbvie, AstraZeneca, Janssen, Roche: Other: Advisory Board, Research Funding. Bartlett: Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Forty Seven: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pharmacyclics: Research Funding; Autolus: Research Funding; Seagen: Consultancy, Research Funding; Roche/Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Brice: MSD: Honoraria; BMS: Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Ribrag: Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Argen-X: Research Funding; Epizyme: Honoraria, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Martin Garcia-Sancho: Celgene: Honoraria, Other: travel; Celgene/BMS: Consultancy; Janssen: Honoraria, Research Funding; Incyte: Consultancy; Takeda: Honoraria; Novartis: Consultancy; Kern Pharma: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Eusa Pharma: Consultancy; Clinigen: Consultancy; Kyowa Kirin: Consultancy; Morphosys: Consultancy; Gilead: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Larouche: Gilead: Consultancy. Ando: Astellas Pharma: Honoraria; Celgene: Honoraria; Chugai Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Novartis: Honoraria; Takeda Pharmaceutical: Research Funding. Maria: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Astrazeneca: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). André: Johnson & Johnson: Research Funding; Roche: Other: Travel/accomodation/expenses, Research Funding; Incyte: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; AbbVie: Other: Travel/accomodation/expenses; Celgene: Other: Travel/accomodation/expenses; Takeda: Consultancy, Research Funding. Sehn: Genmab: Consultancy; Novartis: Consultancy; Debiopharm: Consultancy. Izutsu: Takeda: Honoraria, Research Funding; Symbio: Honoraria; Solasia: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; MSD: Research Funding; Kyowa Kirin: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Incyte: Research Funding; Huya Biosciences: Research Funding; Genmab: Honoraria, Research Funding; Fuji Film Toyama Chemical: Honoraria; Eisai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Beigene: Research Funding; Bayer: Research Funding; AstraZeneca: Honoraria, Research Funding; Yakult: Research Funding; Allergan Japan: Honoraria; AbbVie: Honoraria. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Salles: Velosbio: Consultancy; Epizyme: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Loxo: Consultancy; Regeneron: Consultancy, Honoraria; Novartis: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Rapt: Consultancy; Kite/Gilead: Consultancy; Ipsen: Consultancy; Miltneiy: Consultancy; Genmab: Consultancy; Janssen: Consultancy; Genentech/Roche: Consultancy; Debiopharm: Consultancy; Allogene: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-148218

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. 138, No. Supplement 1 ( 2021-11-05), p. 232-232

Abstract: Background In contrast to the high cure rates in young patients (pts) treated with anthracycline-based chemotherapy, classical Hodgkin lymphoma (cHL) prognosis is poor in elderly pts, and very few data exist for pts considered too frail to receive standard-dose chemotherapy. In those patients, limited therapeutic options are available. Among the new immune-oncology drugs, Nivolumab, an anti-PD1 antibody, has demonstrated high response rate and very good tolerance, and is now approved in relapse and refractory (R/R) cHL. However, data on its use in the frontline setting are scarce. Material and methods We designed a prospective, open-label, multi-centric phase II study, to assess the efficacy and safety of nivolumab alone, or in combination with vinblastine in naive pts aged 61 years and older, with cHL and coexisting medical conditions. Pts were eligible if they had a Cumulative Illness Rating Scale-Geriatric (CIRS-G) score of 6 or more. Treatment consisted in an induction phase of 6 nivolumab injections, delivered at a flat dose of 240 mg every 14 days. Early assessment was done at 12 weeks by PET-CT and CT-scan. Pts who achieved complete metabolic response (CMR) at early assessment completed treatment with nivolumab monotherapy for 18 additional cycles (consolidation phase). Pts who obtained partial metabolic response (PMR) or non metabolic response (NMR, stable disease) received a combination of 18 cycles of nivolumab plus vinblastine, administered intravenously. The primary objective of the study was to assess the CMR rate based on central review at the end of treatment (EOT). Results From August 30th, 2018 to April 28 th, 2020, 64 pts were included in 31 centers, which composed the full analysis set (FAS), used for safety evaluation. Among these 64 pts, 56 pts were fully evaluable and constituted the efficacy set (ES) used for the efficacy analysis (8 pts progressed early or were not assessed by PET-CT). The median age at inclusion in the ES was 75 years [range: 62-91]. Patients had a median CIRS-G score of 10 [range: 6-18] at baseline, and a median G8 score of 12.5 [range: 6-17]. Seventy-three percent of pts had a stage III-IV disease and 42.9% of pts had B symptoms. At EOT, 16 pts (28.6%) achieved CMR according to central PET-CT review. Ten pts (17.9%) achieved PMR, 10 pts were in NMR (17.9%) and progressive metabolic disease was observed in 17 pts (30.4%). Three pts were not evaluated. The overall response rate at end of induction was 51.9%, (9 CMR and 18 PMR). 23 pts received a consolidation with nivolumab and vinblastine. With a median follow-up of 20.1 months, median PFS was 9.8 months [95% CI: 4.2;12] . 15/64 pts of the FAS died during treatment (23.4%): 6 pts from lymphoma, 2 pts from toxicity of study treatment and 2 pts from concurrent illness. One patient died from toxicity of additional treatment after progression, and 4 pts from other causes. The 2-year overall survival was 76.7% [95% CI: 59.6;87.3]. 49/64 pts (76.6%) experienced at least one AE, among which 32 pts experienced grade 3-4 AEs. The 3 more frequent grade 3-4 AEs were neutropenia (8 pts), sepsis (7 pts) and respiratory tract infection (5 pts). Adverse events were related to nivolumab in 36 pts and led to treatment discontinuation in 19 pts (29.7%). Adverse events of special interest i.e., immune-related AEs, were recorded in 22 pts, including 3 pneumonitis, 1 myocarditis, 1 encephalitis and 1 colitis. Among the 64 pts of the FAS, 34% of pts completed the treatment. The median number of cycles administered was 7 [range: 1-24] for nivolumab and 17 [range: 1-18] for vinblastine. Conclusion The NIVINIHO study is the first study to assess the efficacy and safety of an immune checkpoint inhibitor for first line therapy in elderly, frail patients with cHL. The results suggest that in this setting, a nivolumab-based therapy is active in a subset of pts. Further studies and biological analysis are planned to determine which patients may benefit from this approach. Figure 1 Figure 1. Disclosures Lazarovici: Mundipharma: Other: Travel grant. Bouabdallah: Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Sandoz: Consultancy, Honoraria; Abbvie: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Morschhauser: Roche: Consultancy, Speakers Bureau; Chugai: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Laribi: Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; BeiGene: Other: Personal Fees; Le Mans Hospital: Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Jansen: Research Funding. Feugier: Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Sibon: iQone: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Ribrag: Gilead: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; GSK: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Nivolumab. Presently labelled for relapse and refractory classical Hodgkin lymphoma and other malignancies

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-147863

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7