Kooperativer Bibliotheksverbund

In: Kidney International, Elsevier BV, Vol. 98, No. 6 ( 2020-12), p. 1519-1529

Type of Medium: Online Resource

ISSN: 0085-2538

URL: Article

DOI: 10.1016/j.kint.2020.07.042

Language: English

Publisher: Elsevier BV

Publication Date: 2020

detail.hit.zdb_id: 2007940-0

In: Annals of Intensive Care, Springer Science and Business Media LLC, Vol. 7, No. S1 ( 2017-1)

Type of Medium: Online Resource

ISSN: 2110-5820

URL: Article

DOI: 10.1186/s13613-016-0223-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2617094-2

In: Leukemia, Springer Science and Business Media LLC, Vol. 36, No. 12 ( 2022-12), p. 2835-2844

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-022-01711-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2008023-2

In: Blood Advances, American Society of Hematology, Vol. 5, No. 19 ( 2021-10-12), p. 3862-3872

Abstract: Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P & lt; .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P & lt; .001) and mucositis (22.8% vs 3.9% vs 1.8%; P & lt; .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2021004778

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 2876449-3

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 20-21

Abstract: Introduction: Primary mediastinal B cell lymphoma (PMBL) is clinically and biologically distinct from the other subtypes of diffuse large B cell lymphoma (DLBCL), typically affecting young female patients (pts) with a bulky mediastinal mass. Standard treatment (TRT) is a combination of anti-CD20 antibody (Ab) and anthracycline-based chemotherapy. We aimed to compare patients' outcomes after CHOP delivered every 21 days (CHOP21) or 14 days (CHOP14) or ACVBP combined with anti-CD20 Ab in real life. Methods: All Pts treated in LYSA centers were eligible in this retrospective analysis. Inclusion criteria were as follow: age ≥18 years (yrs), newly diagnosed PMBL, TRT with CHOP or ACVBP plus anti-CD20 Ab between 2006 and 2017, and patient non-opposition statement. Primary endpoint was progression-free survival (PFS), secondary endpoints were: overall survival (OS), response rate (Lugano 2014) and total metabolic tumor volume (TMTV). Results: 313 pts were enrolled from 25 LYSA centers in France and Belgium. In all, median age at diagnosis was 32 (18-88) yrs. Majority of pts were female pts (60.7%) and presented at diagnosis with a good performance status (0-1: 81.8%), stage I-II (57.5%), elevated LDH (85%), Bulk & gt;10cm (58.5%) and low/low-intermediate aaIPI 0-1 (56.7%). Pts in the CHOP21 (n=57) group were older (median 40 yrs, vs 33 vs 29.5, p & lt;0.001), had more frequent low/low-intermediate risk aaIPI (71.4%, vs 55.6% vs 52.5%, p=0.044) and displayed a lower proportion of elevated LDH (66.7%, vs 88.2% vs 83.9%, p=0.014) as compared to CHOP14 (n=76) and ACVBP (n=180), plus anti CD20 Ab (Rituximab: n=296, obinutuzumab: n=17). 229 pts (73.2%) received intrathecal prophylaxis. Median number of chemotherapy cycles for CHOP21, CHOP14 and ACVBP groups were: 6 (1-8), 7.5 (1-8) and 4 (1-4), respectively. Consolidation ASCT was performed for 1 (1.8%), 24 (31.6%) and 46 (25.6%) pts, (p & lt;0.001) and mediastinal RT was delivered to 2 (3.5%), 11 (14.5%) and 4 (2.2%) pts, respectively (p & lt;0.001). ASCT + RT was done for 0, 5 (6.6%) and 3 (1.7%) pts, respectively (p=0.043). Baseline TMTV assessment was available for 233 pts (74.4%). Complete metabolic response rates at end of TRT were comparable between CHOP21, CHOP14 and ACVBP groups: 81.1%, 90.9%, and 85.5%, respectively (p=0.46). 37 (11.8%) pts progressed including 32 (10.2%) who displayed primary refractory disease and 6 (16.2%) pts who relapsed after consolidation ASCT. CNS relapse occurred in 9 (2.9%) pts. Median time between ASCT and relapse was 3 (2-58) months. Patients received the following salvage TRTs: high dose chemotherapy (HDC: R-ICE/R-DHAOX-like) (n=30) followed by second-line consolidation ASCT (n=11/30) and post-ASCT mediastinal RT (n=5/11); salvage RT without chemotherapy (n=1); other regimens (R-CHOP, R-GEMOX) (n=3); none (n=3). 2-yrs second PFS (PFS2) rates in pts who had previously received CHOP21, CHOP14 and ACVBP were: 20.5% vs 62.5% vs 18.8% (p=0.43). Only HDC + ASCT strategy granted disease control (2-yrs PFS2: 32.3%). Median follow up was 44 (1-153) months and the CHOP21, CHOP14, ACVBP 5-yrs PFS and 5-yrs OS were: 74.7% (95%CI: 64-97.1%), 89.4% (82.7-96.6%), 89.4% (84.8-94.2%) (p=0.018, Figure A); and 81% (70-94.4%), 100% (100-100%), 92.4% (88.4-96.7%) (p=0.0036, Figure B), respectively. In a multivariate model including TRT group, consolidation ASCT and/or RT, aaIPI, Bulk & gt;10cm and TMTV≥360cm3, CHOP14 was not associated with better PFS as compared to ACVBP and CHOP21 (p=0.1548). Baseline higher TMTV (≥ 360 cm3) was associated with lower PFS in multivariate analysis, independently of TRT (HR=0.41 [0.2-0.85], p=0.02). All grades TRT-related adverse events were similar between the groups, except for an excess of febrile neutropenia (5.3% vs 5.3% vs 24.4%, p & lt;0.001) and mucositis (1.8% vs 3.9% vs 22.8%, p & lt;0.001) in the ACVBP group. Twenty-two pts died (CHOP21: n=8, ACVBP: n=14) mainly due to lymphoma progression (n=15; 68.2%). 2 toxic deaths were observed (CHOP21: n=1, ACVBP: n=1). Secondary malignancies appeared in 7 pts (CHOP21: n=2, ACVBP: n=5), including 3 cases of acute myeloid leukemia. Conclusion These results confirm the favorable outcome of PMBL pts treated with CHOP14 and ACVBP plus anti CD20 Ab. The toxicity of ACVBP was more pronounced and CHOP14 was associated with a better OS. Baseline TMTV≥360cm3 is a highly predictive factor of unfavorable outcome in PMBL pts, independently of TRT. We recommend R-CHOP14 as standard of care in PMBL. Figure Disclosures Camus: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AMGEN: Honoraria; JANSSEN: Honoraria. Decazes:Bayer: Other: travel, accomodations, expenses. Bernard:Janssen: Other: Travel and accommodation . Gandhi Laurent:Abbevie, Pfizer, Takeda, Roche: Other: Travel; Roche, Takeda, Iqone, Accord: Consultancy; Roche, Takeda, Accord: Honoraria. Laribi:amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding; abbvie: Honoraria, Research Funding. Houot:Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; MSD: Honoraria. Tilly:BMS: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136600

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. 128, No. 22 ( 2016-12-02), p. 2039-2039

Abstract: INTRODUCTION: The benefits of ibrutinib (ibr) have been demonstrated by the phase 3 RESONATE and RESONATE-2 trials for patients (pts) with R/R and TN (≥ 65 years) CLL, respectively. In these studies, ibr showed significantly improved progression-free survival (PFS) and overall survival (OS) vs approved comparators (ofatumumab [ofa] in RESONATE and chlorambucil [clb] in RESONATE-2). However, a number of other treatment regimens are widely used in clinical practice for CLL based on individual patient and disease characteristics; it is currently unknown if ibr results in better survival outcomes when compared directly with each of these other treatments. AIM: In the absence of a head-to-head comparison, we investigated the relative efficacy of ibr vs physician's choice (PC) in pts with R/R or TN CLL by comparing pt-level data from RESONATE and RESONATE-2 with data from pts in a real-world setting (the Lyon-Sud database). This database holds electronic medical records for 390 pts with CLL from the academic Lyon-Sud Hospital in France; nearly all patients were diagnosed between 1990 and 2014. This is the first analysis of ibr vs PC in a real-world setting for pts with TN CLL. METHODS: Pt-level data from RESONATE (ibr, n = 195; ofa, n = 196) were compared with data on pts with CLL from Lyon-Sud who received 2nd(n = 107) or later-line treatment (3rd [n = 62], 4th [n = 43] , and subsequent [n = 51] lines). Similarly, RESONATE-2 (ibr, n = 136; clb, n = 133) pt-level data were compared with those of pts aged ≥ 65 years who received 1st-line treatment (n = 131). In order to account for non-comparability due to lack of randomization, a multivariate Cox proportional hazards model was used to compare PFS and OS between treatments, including line of therapy, age, sex, disease stage (based on Binet/Rai), and deletion 17p or 11q mutations as covariates. For the definition of PFS, missing data for date of disease progression for pts in Lyon-Sud who initiated subsequent therapy were replaced by the conservative proxy of date of initiation of next treatment. Predicted PFS and OS curves for the Lyon-Sud cohort were derived from the multivariate model. RESULTS: For R/R pts in Lyon-Sud, across all treatment lines the most frequent regimens used were rituximab (R) + chemotherapy (n = 46), bendamustine + R (BR; n = 28), fludarabine + cyclophosphamide + R (FCR) (n = 27), clb + R (n = 19), R monotherapy (n = 21), and R-CHOP-based (n = 19); the remaining percentages comprised various other therapies, each used in 〈 5% of pts. Median age at treatment initiation for Lyon-Sud and RESONATE was 69 and 67 years, respectively; median number of prior therapies was 2 and 3, and median follow-up was 30.0 and 21.9 months. More lines of prior therapy, older age, male sex, advanced disease stage (Binet C/Rai III/IV), and presence of deletion 17p/11q were independent risk factors for worse PFS and OS outcome. After adjustment for differences in baseline characteristics, PFS and OS hazard ratios (HRs) for ibr vs PC were 0.18 (95% confidence interval [CI], 0.13-0.26) and 0.28 (0.17-0.46), respectively. Adjusted HRs for ibr vs the most frequent treatments ranged from 0.09 (R monotherapy) to 0.38 (FCR) for PFS and 0.21 (R monotherapy) to 0.33 (FCR) for OS; all were statistically significant. For TN pts in Lyon-Sud, the most frequent treatment regimens used were FCR (n = 40), clb + R (n = 21), clb monotherapy (n = 17), R-(mini)CHOP (n = 11), and BR (n = 11). Median age at treatment initiation was 73 years for both Lyon-Sud and RESONATE-2; median follow-up was 36.9 and 28.1 months, respectively. Older age, male sex, and advanced disease stage were independent risk factors for worse PFS and OS outcome. After adjustment for baseline differences, the PFS and OS HRs for ibr vs PC were 0.25 (0.14-0.47) and 0.41 (0.17-0.99). Predicted PFS and OS curves for both R/R and TN patients are presented in Figure 1. CONCLUSIONS: Investigation of survival outcomes suggests that ibr administered to pts in RESONATE and RESONATE-2 was more effective than PC used in a real-world cohort of French pts with R/R or TN CLL, suggesting a 4.8-fold improvement in PFS and a 3.4-fold improvement in OS in R/R pts and 4-fold and 2.4-fold improvements in TN pts, respectively. These results further support the growing evidence that ibr significantly improves both PFS and OS vs commonly used regimens in the R/R and TN settings, and could have important implications for improving treatment of CLL in clinical practice. Disclosures Salles: Janssen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding. Sarkozy:Sandoz: Research Funding; Janssen Research & Development: Honoraria; Gilead: Honoraria; Takeda: Research Funding. Ghesquieres:Mundipharma: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche France: Research Funding. Diels:Johnson & Johnson: Employment, Equity Ownership. Besson:Janssen: Employment. MacDougall:Janssen Research & Development: Research Funding; IMS Health: Employment. Hermans:Janssen Research & Development: Research Funding; IMS Health: Employment. Healy:Janssen Research & Development: Employment. Garside:Janssen Research & Development: Employment. Iraqi:Janssen Research & Development: Employment.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.2039.2039

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Leukemia, Springer Science and Business Media LLC, Vol. 37, No. 10 ( 2023-10), p. 2142-2142

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-023-01978-x

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2008023-2

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3332-3332

Abstract: BACKGROUND: The European Commission has granted conditional approval to daratumumab (DARA) as monotherapy in adult patients (pts) with relapsed or refractory multiple myeloma (MM) whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and who have demonstrated disease progression on the last therapy. DARA was approved under an accelerated assessment based on single-arm phase 2 studies. Outcomes in these heavily pretreated pts in a real-world (RW) setting can provide evidence on the relative treatment efficacy of DARA versus physician's choice (PC). AIMS: To perform an adjusted comparison of overall survival (OS) and progression-free survival (PFS) for DARA monotherapy versus PC, as observed in a RW historical cohort of heavily pretreated and highly refractory MM pts from the Czech Republic using pt-level data. METHODS: Using RW longitudinal pt chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, pts with ≥2 prior lines of therapy previously exposed to both a PI and an IMiD were identified. Pt-level data from the RMG were pooled from pivotal DARA monotherapy studies (pts treated with DARA 16 mg/kg). Pts in the RMG could contribute information to the analysis for multiple lines of therapy, with baseline defined as the date of initiation of the actual treatment line. For the definition of PFS, missing data for the date of disease progression for pts in the RMG who initiated subsequent therapy were replaced by the conservative proxy of the date of initiation of the next treatment. OS and PFS were analysed using a Kaplan-Meier analysis. To adjust for confounding variables, a multivariate Cox proportional hazards regression was developed that included age, gender, beta-2 microglobulin levels (β2M : & lt;3.5/3.5-5.5/ & gt;5.5 g/L), albumin levels ( & lt;3.5/≥3.5 g/L), line of therapy (3-13), prior exposure to pomalidomide/carfilzomib, refractory status (none/double/triple/quadruple), andincidence of thrombocytopenia (defined as platelet counts & lt;150.000 per µL) as covariates. Predicted PFS and OS curves for the RMG cohort were derived from the multivariate model. RESULTS: From the RMG database, we identified 971 treatment lines in 463 pts previously exposed to both a PI and an IMID (n=206 in third line, n=256 in fourth line, n=203 in fifth line, n=307 in ≥sixth line). The dates of treatment initiation for the RMG pts ranged from March 2006 to March 2015. The most frequent treatment regimens were lenalidomide (33.4%), chemotherapy (18.1%), bortezomib (13.6%), thalidomide (8.0%), and bortezomib+thalidomide (5.3%). The number of pts treated with carfilzomib (2.5%) and pomalidomide (2.4%) was limited. DARA-treated pts (N=148) differed from the RMG cohort in median age (64 vs 62 years), median prior lines of therapy (5 vs 4), prior exposure to carfilzomib (41.2% vs 0.3%) and pomalidomide (55.4% vs 0.6%), thrombocytopenia incidence (46.9% vs 18.0%), and ≥triple refractory status (64.2% vs 5.3%). Median observed PFS and OS for DARA versus PC were 4.0 and 5.6 months, respectively, for PFS and 20.1 and 11.9 months, respectively, for OS. Older age, male sex, low albumin levels, high β2M levels, thrombocytopenia incidence, and double/triple/quadruple refractory status were all independent, statistically significant risk factors for mortality. Albumin levels, β2M levels, thrombocytopenia incidence, and refractory status were also predictive of PFS. The adjusted hazard ratio (95% confidence interval) for OS and PFS for DARA versus PC was 0.35 (0.22-0.56) and 0.79 (0.56-1.12), respectively. Figure 1 represents the predicted survival curves for the RMG cohort that were derived from the multivariate model, comparing observed PFS/OS versus predicted with DARA treatment. CONCLUSIONS: This adjusted treatment comparison suggests a significant improvement in OS and a numerical improvement in PFS for DARA compared to RW historical control data in heavily pretreated/highly refractory MM pts. The lower PFS benefit estimate for DARA compared to OS may be partly explained by limitations in the availability and comparability of data regarding progressive disease in the RMG cohort compared to clinical trial data. Adjusted comparisons between trial data and historical cohorts can provide useful insights to clinicians and reimbursement decision makers on relative treatment efficacies in the absence of head-to-head comparison studies for DARA monotherapy. Disclosures Hájek: Amgen: Honoraria, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Spicka:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gatopoulou:Janssen Health Economics & Market Access EMEA: Employment. Vesela:Janssen Cilag s.r.o., Czech Republic: Employment. Diels:Johnson & Johnson: Employment, Equity Ownership. Besson:Janssen: Employment. Ito:Janssen: Employment, Equity Ownership.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.3332.3332

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

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. 130-130

Abstract: Introduction: Patients (pts) with HIV have a 6-fold increased risk of developing classic Hodgkin lymphoma (cHL) over the general population. The outcome of frontline therapy for HIV-associated cHL (HIV-cHL) using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is similar to the non-HIV population. However, pts with advanced stage cHL continue to have a 30% chance of refractory/relapsed disease with ABVD. Brentuximab vedotin (BV) is an anti-CD30 antibody drug conjugate that selectively induces apoptosis of CD30+ cells. The FDA approved BV with AVD (BV-AVD) after the Echelon-1 (E1) study for advanced stage disease demonstrated improved modified progression free survival (mPFS) at 2 years compared with standard ABVD: 82% vs. 77%. Pts with HIV were excluded from both relapsed/refractory and frontline BV trials. Here we present the final results of the phase 2 trial of BV-AVD in previously untreated HIV-associated cHL, an AIDS Malignancy Consortium/LYSA collaboration (ClinicalTrials.gov ID: NCT01771107). Methods: Forty-one pts were treated on days 1 and 15 of 6, 28 day cycles, with 1.2mgs/kg of BV in combination with doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 (AVD). Eligibility criteria included untreated cHL stage II-IV, CD4 + T-cell counts ≥50 cells/mm3, and initiation of combined antiretroviral therapy (cART) at least 1 week prior to therapy. Ritonavir, zidovidine, cobisistat, and other strong CYP3A4 or P-glycoprotein inhibitors were excluded with a washout of at least 1 week being required. Hematopoietic growth factor was mandated. The primary objective was 2 year PFS. The sample size was based on providing an estimate of the PFS with a 95% CI +/- 10% under the assumption of a 2 year progression free survival (PFS) estimate of 85%. Secondary objectives included toxicity, effects on CD4/CD8 + T-cells, HIV-1 viral load, prognostic significance of post C2 and end of treatment PET-CT. Results: Forty-one pts (93% men) were treated with a median age of 48y (range 24-67). Pts presented with stage II (17%), III (27%), and IV (56%) disease. Two year PFS estimate in the overall population (N=41) was 86% (95% CI: .74, .98). The 2-year overall survival (OS) estimate was 92% (95% CI: 0.83, 1.0) with 3 deaths at the time of analysis, including 1 which was a treatment related death (Figure 1A). For pts with advanced disease (N=34), the 2-year PFS estimate was 87% (95% CI: 0.76, 0.99) with an OS estimate of 90% (95% CI: 0.8, 1.00) (Figure 1B). Safety profiles were quite similar to the BV-AVD arm in the E1 study of the pts who received growth factor. Neuropathy was higher in our study compared to E1, (49% vs. 29% for any grade, P=0.01; 9.8% vs. 5% for G3/4, p=0.06). G3 Neutropenia was greater in AMC 085 compared to E1 BV-AVD arm with growth factor: 57% vs. 29% (p & lt;0.01). The outcomes between this study and E1 with respect to serious adverse events due to infection (33% vs. 44%) or febrile neutropenia (11% vs. 15%) during therapy were similar. Two pts were removed from study for violating inclusion criteria by taking ritonavir, a strong CYP 3A4 inhibitor since enrollment. One developed febrile neutropenia and G4 pancreatitis cycle 1 day 7 while the second developed febrile neutropenia prior to cycle 2. A third pt discontinued ritonavir 2 days prior to enrollment and developed a prolonged G3 neuropathy. The median CD4 and CD8+ T-cell counts at diagnosis were 289 cells/mm3 (range 32-818) and 486 cells/mm3 (range 26-1780), respectively. Of evaluable pts an increase in CD4 and CD8+ T-cell counts were noted just 1 month after therapy to 545 cell/mm3 (range161-2130) and 745 cell/mm3 (range 132-3106) noted by cycle 2 day 1. Sixty-nine % had undetectable viral loads at baseline. For those with detectable viral loads at diagnosis, the median viral load was 52 copies/ml (range 22-15,706). HIV-1 viral loads declined during therapy. PET/CT data demonstrated 3/32 pts were PET positive after cycle 2. One of 29 pts was PET/CT positive by end of cycle 6 deemed to be a false positive based on benign biopsy and follow up. Conclusions: BV-AVD in stage II-IV HIV-cHL was efficacious although neutropenia and neuropathy were increased compared to the non-HIV population. The 2-year PFS estimate was 86% for the entire cohort and 87% for advanced stage HIV-cHL. Major interactions with strong CYP3A4 inhibitors lead to toxicity and must be avoided. The etiology of the CD4 increase is under investigation and may have implications for future therapy. Disclosures Rudek: Cullinan Apollo: Research Funding; Taiho: Research Funding; RenovoRX: Research Funding; Celgene: Research Funding. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Noy:Medscape: Honoraria; Janssen: Consultancy; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. OffLabel Disclosure: Brentuximab Vedotin has been approved for the upfront treatment of advanced stage cHL in combination with AVD though not specifically approved for use in patients infected with HIV or stage 2 cHL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-126787

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. 132, No. Supplement 1 ( 2018-11-29), p. 1604-1604

Abstract: Introduction Ibrutinib, a first-in-class, oral, covalent inhibitor of Bruton's tyrosine kinase, is approved in several countries as monotherapy for adults with WM, based on the high response rate (90.5%) observed in a phase 2, single-arm trial of symptomatic patients who had received ≥ 1 prior therapy (NCT01614821; Treon SP, et al. N Engl J Med. 2015;372:1430-1440). In the phase 3 iNNOVATE trial (NCT02165397; Dimopoulos MA, et al. N Engl J Med. 2018;378:2399-2410), adding rituximab to ibrutinib (IR) led to a statistically significant improvement in progression-free survival (PFS) compared with placebo-rituximab, in both treatment-naïve (TN) patients and those with disease recurrence. This analysis examined the relative treatment effect of IR versus other RW treatment regimens used in daily clinical practice in TN and relapsed/refractory (R/R) WM. An adjusted comparison was conducted using patient-level data from the iNNOVATE trial and the Lyon-Sud RW database in France. Methods The Lyon-Sud database holds medical records for patients with WM diagnosed between 1980 and 2017 from the Centre Hospitalier Lyon-Sud. PFS and overall survival (OS) outcomes were compared between the IR arm of iNNOVATE and RW physicians' choice (PC) treatment in Lyon-Sud (excluding RW ibrutinib). Kaplan-Meier survival curves by patient cohort were generated for both end points. A multivariate Cox proportional hazards model was fitted on the pooled patient-level data from both sources to estimate adjusted hazard ratios (HRs) for effect of IR on PFS and OS versus RW treatment, with age, sex, and treatment line as covariates. The unit of observation for the RW databases was the treatment line (rather than the patient) number, whereby RW patients receiving multiple treatment lines contributed to multiple observations, and baseline was defined as the line-specific treatment start date. Results Overall, 242 treatment lines from patients with WM were identified from the Lyon-Sud database; 224 were analyzed. Baseline characteristics were comparable between the IR arm of iNNOVATE (n = 75) and the RW cohort: 62.7% versus 66.5% ≥ 65 years of age; line of therapy, 45.3% versus 48.7% TN [1L], 25.3% versus 25.0% second-line [2L] , and 29.3% versus 26.3% third-line or later [3L+]. Median follow-up was 26.7 months for iNNOVATE and 68.5 months for the RW cohort. Non-ibrutinib PC regimens in the RW cohort included rituximab (n = 51 treatment lines), chemotherapy (n = 66; including chlorambucil, n = 31), rituximab-cyclophosphamide-dexamethasone (n = 35), rituximab-CHOP/CHOP-like (n = 21), rituximab-chlorambucil (n = 15), fludarabine-cyclophosphamide-rituximab (n = 14), bendamustine-rituximab (n = 10), other rituximab-containing chemoimmunotherapy (n = 10), and rituximab-targeted agent (n = 2). Two ibrutinib lines were excluded from the RW cohort analysis. Figures A and B show the observed 1L+ Kaplan-Meier curves for IR versus RW PC therapy for all analyzed patients with WM (unadjusted HRs: 0.32 [95% confidence interval (CI), 0.19-0.55] for PFS and 0.38 [95% CI, 0.13-1.09] for OS). After adjusting for differences in patient characteristics, HRs (1L+ therapy) became 0.28 (95% CI, 0.16-0.48; p 〈 0.001) for PFS and 0.29 (95% CI, 0.09-0.93; p = 0.037) for OS. Restricting the analysis to 1L treatment only (Lyon-Sud n = 109; iNNOVATE n = 34), the adjusted HRs were 0.25 (95% CI, 0.09-0.70; p 〈 0.009) for PFS and 0.20 (95% CI, 0.02-2.00; p = 0.170) for OS; respective unadjusted HRs were 0.31 (95% CI, 0.12-0.78) and 0.30 (95% CI, 0.04-2.34). In the 2L+ setting (Lyon-Sud n = 115; iNNOVATE n = 41), the adjusted HRs were 0.28 (95% CI, 0.15-0.56; p 〈 0.001) for PFS and 0.34 (95% CI, 0.08-1.35; p = 0.126) for OS; respective unadjusted HRs were 0.31 (95% CI, 0.16-0.61) and 0.39 (95% CI, 0.12-1.31). Concl usions In the absence of randomized controlled trial data for ibrutinib versus other treatment regimens for WM, these adjusted comparisons of clinical trial and RW patient-level data suggest that IR significantly improves both PFS and OS versus RW PC regimens as 1L+ therapy. These results help inform physicians on the standard of care for WM in clinical practice. Funding Source: This project was sponsored by Janssen Pharmaceutica NV, and Pharmacyclics LLC, an AbbVie Company. The real-world databases are independently owned. Writing assistance was provided by Emma Fulkes of PAREXEL and funded by Janssen Pharmaceutica NV. Disclosures Karlin: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Besson:Janssen Pharmaceutica NV: Employment. Tapprich:Janssen Pharmaceutica NV: Employment. Garside:Janssen Pharmaceutica NV: Employment. Salles:Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; AbbVie: Honoraria; Acerta: Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria; Merck: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Servier: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Epizyme: Honoraria; Morphosys: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112203

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

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detail.hit.zdb_id: 80069-7