DREAMM-2: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) and renal impairment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8519-8519 ◽  
Author(s):  
Hans Chulhee Lee ◽  
Adam D. Cohen ◽  
Ajai Chari ◽  
Malin Hultcrantz ◽  
Ajay K. Nooka ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Single Agent ◽  
Similar Efficacy ◽  
Poor Prognostic Factor ◽  
B Cell Maturation ◽  
Duration Of Response ◽  
Function Table ◽  
Mild Impairment ◽  
Post Hoc

8519 Background: Renal impairment, a frequent complication and poor prognostic factor in RRMM, often leads to poor tolerability of standard regimens. We report outcomes in patients with renal impairment receiving single-agent belantamab mafodotin (2.5 or 3.4 mg/kg; B-cell maturation antigen targeting immunoconjugate not renally metabolized) from the DREAMM-2 post-hoc analysis (NCT03525678). Methods: Eligible patients with RRMM had no active renal conditions and adequate renal function (based on albumin/creatinine ratio [<500 mg/g] and eGFR [mL/min/1.73 m2]: normal [≥90], mild impairment [mild, ≥60≤90], moderate impairment [mod, ≥30≤60]). Results: Overall response rates (95% CI) in patients with mild/mod impairment (2.5 mg/kg: 32% [21.4–44.0]; 3.4 mg/kg: 36% [25.6–48.5]) were similar to those in the overall population ( Lancet Oncol.2020). The median duration of response (DoR) was not reached (NR) in 2.5 mg/kg mild/mod subgroup (95% CI estimate: 4.2 months–NR); median DoR was 7.5 months (4.9–NR) in 3.4 mg/kg mild/mod subgroup. Rates of keratopathy and albuminuria were similar regardless of renal function; rates of anemia, pyrexia, and thrombocytopenia were more frequent in patients with impaired renal function (Table). eGFR did not change or changed to normal in most patients. Conclusions: Following treatment with single-agent belantamab mafodotin, patients with mild/mod renal impairment achieved a similar efficacy and safety profile as patients with normal renal function. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]

scholarly journals Dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: a post hoc analysis of the ATHENA trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Vamos ◽  
J Oldgren ◽  
G.-B Nam ◽  
G Lip ◽  
H Calkins ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Funding Source ◽  
Efficacy And Safety ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is challenging due to issues with renal clearance, drug accumulation and increased proarrhythmic risks. Since CKD is a common comorbidity with atrial fibrillation (AF), it is important to establish the efficacy and safety for antiarrhythmic drug treatment in patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or atrial flutter (AFL) across different stages of renal impairment. Methods In this post-hoc analysis of ATHENA (NCT00174785), a randomised, double-blind trial of dronedarone 400 mg BID vs placebo in patients with AF or AFL plus additional risk factors for death and a calculated glomerular filtration rate ≥10 mL/min, the primary outcome was time to first cardiovascular (CV) hospitalisation or death. Renal function (estimated glomerular filtration rate [eGFR]) was assessed using CKD Epidemiology Collaboration equation and patients were grouped by eGFR (10–44, 45–59, ≥60 mL/min). Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results In ATHENA, 43.6% of placebo and 42.2% of dronedarone patients had mild-to-moderate CKD (Table). Median time to CV hospitalisation/death was longer in all strata for dronedarone vs placebo, reaching significance in the 45–59 and ≥60 mL/min groups (Figure 1). There was a trend towards more treatment-emergent adverse events (TEAEs), deaths and discontinuations due to TEAEs in patients with eGFR 10–44 mL/min. No clear difference in safety was seen between treatment arms except for discontinuations, which were higher with dronedarone. Conclusions This analysis confirms the efficacy of dronedarone, demonstrated in ATHENA, across different stages of renal impairment. Further assessment of safety will require larger populations of patients with CKD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

Phase III trial of gemcitabine plus docetaxel (GD) compared to capecitabine plus docetaxel (CD) with planned crossover to the alternate single agent in metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1000-1000
Author(s):  
A. D. Seidman ◽  
A. Brufsky ◽  
R. H. Ansari ◽  
J. R. Rubinsak ◽  
R. S. Stein ◽  
...  
Keyword(s):  
Single Agent ◽  
Metastatic Breast ◽  
Similar Efficacy ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Post Hoc

1000 Background: GD and CD are efficacious in patients (pts) with MBC. This study compared safety and efficacy of GD and CD induction regimens, where the alternate, single-agent, crossover therapy (GD to C or CD to G) was predetermined. Primary endpoint was time to progressive disease (TTP). Secondary endpoints included toxicities, overall response (ORR), and overall survival (OS). Methods: This multicenter, open-label, phase III study enrolled MBC pts with possible prior anthracycline therapy, adjuvant or neoadjuvant taxane therapy, but no taxane therapy for MBC ≤6 months prior to entry. Enrollment of 442 pts (221 per arm) was planned with 385 progressions required to achieve 80% power for a 2-month observed difference in median TTP between arms. Pts were randomized to: GD: G 1,000mg/m2 Days 1, 8 plus D 75 mg/m2 Day 1, q21 days; or CD: C 1,000 mg/m2 BID, Days 1–14 plus D 75 mg/m2 Day 1, q 21 days. Upon disease progression, pts were given crossover C or G at doses and schedules identical to induction. ORR was assessed by RECIST. Results: Demographics of 472 enrolled pts were balanced between arms; 57% had prior anthracycline. GD caused greater myelosuppression than CD, but without greater febrile neutropenia. Gastrointestinal toxicities, mucositis, and hand-foot syndrome were greater with CD. More pts in the CD arm (n=61, 26.2%) versus the GD arm (n=41, 17.2%) discontinued due to toxicity (p=0.023). ORR, TTP, and OS were not significantly different comparing GD and CD. However, ORR and TTP were significantly greater for the GD to C crossover monotherapy compared to CD to G. Post-hoc analysis of crossover pts showed that the TTP sum from induction through crossover was 6.1 months greater for GD to C. Conclusions: GD and CD had similar efficacy with toxicity profiles consistent with prior clinical experience. Results suggest that the GD to C crossover sequence may provide a clinical benefit over CD to G. [Table: see text] [Table: see text]

DREAMM-2: Assessing efficacy via indirect comparison of single-agent belantamab mafodotin versus selinexor plus dexamethasone combination in anti-CD38 exposed relapsed/refractory multiple myeloma (RRMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20527-e20527
Author(s):  
Rakesh Popat ◽  
Attaya Suvannasankha ◽  
Venediktos Kapetanakis ◽  
Thibaud Prawitz ◽  
Grammati Sarri ◽  
...  
Keyword(s):  
Patient Population ◽  
Single Agent ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Data Availability ◽  
B Cell Maturation ◽  
Similar Patient ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Pretreated Patients

e20527 Background: Single-agent belantamab mafodotin (GSK2857916) is a first-in-class immunoconjugate targeting B-cell maturation antigen that demonstrated deep and durable responses in heavily pretreated patients with RRMM in the pivotal DREAMM-2 study (NCT03525678; Lancet Oncol 2020). Methods: DREAMM-2 included patients with late-line RRMM treated with ≥3 prior lines of therapy, refractory to an immunomodulatory agent and a proteasome inhibitor, with prior exposure to an anti-CD38 antibody. Evidence from Phase II/III trials in a similar patient population was systematically identified following PRISMA guidelines. Based on the specificity of the DREAMM-2 population, selinexor plus low-dose dexamethasone (sel+dex) was identified as the only feasible comparator (STORM Part 2, NCT02336815). Matching-adjusted indirect comparisons (MAIC) were used to investigate the efficacy of single-agent belantamab mafodotin vs. sel+dex. Populations were matched for all clinically validated effect modifiers and prognostic factors with available data. MAIC were performed for overall response rate (ORR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS), as per NICE guidelines. Results: Single-agent belantamab mafodotin was more efficacious than sel+dex in terms of OS and DoR (Table). Results for ORR, TTR, and PFS showed no statistical difference between the two regimens. Conclusions: MAIC of single-agent belantamab mafodotin vs. sel+dex in this patient population with RRMM showed significantly improved efficacy on OS and DoR for belantamab mafodotin. Further validation is required owing to limited data availability. Additional safety analyses will further inform comparisons of the two. Clinical trial information: NCT03525678; NCT02336815. Funding: GlaxoSmithKline (207145). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. [Table: see text]

Relationship between corneal exam findings, best-corrected visual acuity (BCVA), and ocular symptoms in patients with relapsed or refractory multiple myeloma (RRMM) receiving belantamab mafodotin (belamaf).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8033-8033
Author(s):  
Evangelos Terpos ◽  
Ashraf Badros ◽  
Rakesh Popat ◽  
Paula Rodríguez-Otero ◽  
Asim Farooq ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Corneal Epithelium ◽  
Single Agent ◽  
Antibody Drug Conjugate ◽  
Ocular Symptoms ◽  
B Cell Maturation ◽  
Snellen Visual Acuity ◽  
Patient Reported ◽  
The Us ◽  
Post Hoc

8033 Background: Belantamab mafodotin (GSK2857916; belamaf; BLENREP) is a B-cell maturation antigen (BCMA)-targeting antibody–drug conjugate approved in the US and EU as a monotherapy for the treatment of adult patients with RRMM. Ocular events (OEs) during the pivotal DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Here we performed a post hoc investigation of relationships between corneal exam findings, BCVA changes, and patient-reported ocular symptoms to explore if BCVA changes and symptoms could guide dosing, rather than corneal exams. Methods: Eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ophthalmologists at baseline and prior to each belamaf dose. Changes in the corneal epithelium (Ker) and BCVA were both assessed as per protocol-defined criteria and assessment of grade (Gr) was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported as per the Common Terminology Criteria for Adverse Events. Results: In 12.5% of eye evaluations Gr 3–4 Ker was associated with minimal or no (Gr ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Gr 3–4 Ker with Gr ≤1 BCVA changes or ocular symptoms. Mild or no (Gr ≤2) Ker was associated with Gr ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Gr 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Gr 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Association of corneal epithelium changes (Ker) with BCVA changes and ocular symptoms. Conclusions: These findings highlight that BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (eg, frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Clinical trial information: NCT03525678. [Table: see text]

scholarly journals Efficacy and safety of urate-lowering therapy in people with kidney impairment: a GCAN-initiated literature review

2021 ◽  
Author(s):  
Hamish Farquhar ◽  
Ana B Vargas-Santos ◽  
Huai Leng Pisaniello ◽  
Mark Fisher ◽  
Catherine Hill ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Case Reports ◽  
Serum Urate ◽  
Cochrane Library ◽  
Future Studies ◽  
Kidney Impairment ◽  
The Cochrane Library ◽  
Study Designs ◽  
Different Levels

Abstract Objectives To evaluate the efficacy, defined as achieving target serum urate &lt;6.0 mg/dl, and safety of urate-lowering therapies (ULT) for people with gout and CKD stages 3–5. Methods PubMed, The Cochrane Library, and EMBASE, were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of &lt; 60 mL/min, and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for which we did include case reports. Results There were 36 reports with an analysis of efficacy and/or safety based upon renal function – allopurinol (n = 12), febuxostat (n = 10), probenecid (n = 3), benzbromarone (n = 5), lesinurad (n = 5), and pegloticase (n = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function – allopurinol (n = 84), febuxostat (n = 14), benzbromarone (n = 1), lesinurad (n = 3), and pegloticase (n = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of &lt; 30mL/min). For allopurinol in particular, there was significant variability in the dose of drug used, and efficacy in terms of urate lowering, across all levels of renal impairment. Conclusion There is a lack of evidence regarding efficacy and/or safety of currently used ULT according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function.

P0234LOW URINARY CITRATE LEVELS ARE NOT SPECIFIC OF AUTOSOMAL POLYCYSTIC KIDNEY DISEASE (ADPKD) AND ARE PRESENT WHEN RENAL FUNCTION IS IMPAIRED IN ALL NEPHROPATIES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Francisco-Jose Borrego-Utiel ◽  
Enoc Merino Garcia ◽  
Isidoro Herrera ◽  
Clara Moriana Dominguez ◽  
Victoria Camacho Reina ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Polycystic Kidney Disease ◽  
Normal Renal Function ◽  
Serum Bicarbonate ◽  
Polycystic Kidney ◽  
Glomerular Diseases ◽  
Urinary Citrate

Abstract Background and Aims In polycystic kidney disease (PKD) it is frequently found a reduction in urinary citrate that is related with degree of renal impairment but it is unknown if this alteration is specific or if it is also present in other nephropathies. Recently it has been suggested that urinary citrate could be a marker of covert metabolic acidosis and reflects acid retention in chronic kidney disease (CKD). Our aim was to compare urinary citrate in PKD with other renal diseases and to show its relation with serum bicarbonate and excretion of uric acid and calcium. Method We determined citrate, calcium and uric acid in 24-hour urine in patients with PKD and with other nephropathies with varied degree of renal impairment followed in a outpatient clinic of nephrology. Results We included 291 patients, 119 with glomerular diseases, 116 with PKD, 21 with other nephropathies, and 35 patients with normal renal function. Urinary citrate was higher in women (Females 309±251 mg/gCr vs. males 181±145 mg/gCr, p&lt;0.001) and in patients with normal renal function (normal 380±210 mg/gCr; PKD 203±166 mg/gCr; glomerular 279±282 mg/gCr; p&lt;0,001). PKD patients showed similar values of urinary citrate to patients with glomerular diseases and with other nephropathies. We observed a progressive reduction in urinary citrate parallel to degree of renal impairment, in a comparable way among patients with PKD and glomerular diseases. We did not observe a relationship between urinary citrate and serum bicarbonate levels. Calcium and uric acid elimination in ADPKD patients was similar to other nephropathies and lower to patients with normal renal function. However, serum uric acid was significantly higher in glomerular patients than other nephropathies after adjust with glomerular filtration rate and sex. Conclusion Hypocitraturia is not specific of PKD but it is also present in all nephropathies. Urinary citrate are related to degree of renal impairment and it is not related with serum bicarbonate. We think that it could be interesting to study urinary citrate as a marker of renal function and its role as prognostic factor of renal deterioration.

Inducible T-cell co-stimulatory (ICOS) receptor agonist, feladilimab (fela), alone and in combination (combo) with pembrolizumab (P): Results from INDUCE-1 urothelial carcinoma (UC) expansion cohorts (ECs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4519-4519
Author(s):  
Arjun Vasant Balar ◽  
Victor Moreno ◽  
Eric Angevin ◽  
Hui Kong Gan ◽  
Maria Vieito ◽  
...  
Keyword(s):  
T Cell ◽  
Single Agent ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Metastatic Setting ◽  
Duration Of Response ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Tumor Types

4519 Background: INDUCE-1 is a first-in-human trial evaluating fela, an IgG4 ICOS agonist non-T-cell depleting mAb, as monotherapy (mono) and in combo with P. ECs include tumor types, such as UC, with high ICOS expression and immunotherapy-favorable features. Fela induced IFNγ, increased PD-1/L1 expression, and enhanced antitumor activity in combo with PD-1 blockade nonclinically. We report preliminary efficacy, safety, and biomarker data of fela ± P in INDUCE-1 UC ECs. Methods: Eligible patients (pts) had recurrent/metastatic (R/M) UC of the upper or lower urinary tract, ≤6 prior systemic therapy lines in the advanced setting, measurable disease, and no active autoimmune disease. Pts received 0.3 or 1 mg/kg fela (mono EC; anti-PD-1/L1–experienced [exp] pts) or 0.3 mg/kg fela + 200 mg P (combo EC; anti-PD-1/L1–naïve pts) every 3 wks, up to 35 cycles until disease progression or unacceptable toxicity. Disease was assessed every 9 wks through wk 54, then every 12 wks. Archival and/or fresh biopsy tumor tissue was collected for biomarker analyses and safety assessed. Results: By Nov 6 2020, 13 anti-PD-1/L1–exp and 32 anti-PD-1/L1–naïve pts were evaluable in the mono and combo ECs, respectively. In the mono EC, median age was 69 yrs (range: 47–82), 92% of pts were male, and 85% received ≥2 prior therapy lines in the metastatic setting. In the combo EC, median age was 70 yrs (range: 42–84), 75% of pts were male, and 72% received ≥1 prior therapy line in the metastatic setting. In the mono EC, median duration of follow-up (mDoF) was 10.6 mo (range: 1.1–22.8); overall response rate (ORR) was 8% (1 partial response [PR]; 95% CI: 0.2, 36.0) with a duration of response (DoR) of 6.1 mo; disease control rate (DCR [response or stable disease for ≥9 wks]) was 23% (95% CI: 5.0, 53.8), and median overall survival (mOS) was 14.5 mo (95% CI: 2.8, NR), with 74% of pts alive at 6 mo. In the combo EC, mDoF was 9.6 mo (range: 0.9–28.3); ORR was 22% (7 PRs; 95% CI: 9.3, 40.0) with a median DoR of 8.3 months (range: 3.5–23.3+); DCR was 63% (95% CI: 43.7, 78.9), and mOS was 10.7 mo (95% CI: 5.2, 18.1), with 64% of pts alive at 6 mo. Grade ≥3 treatment-related AEs were reported for 0% and 9% of pts in the mono (N = 16) and combo (N = 44) safety populations, respectively. PD-L1 expression and ICOS-specific biomarkers are being evaluated, with promising trends observed in enrichment of clinical activity in preliminary analyses. Conclusions: Fela is the first ICOS agonist with reported single-agent activity in anti-PD-1/L1–exp relapsed/refractory UC. Fela + P in combo shows promising clinical activity and manageable safety in PD-1/L1–naïve R/M UC. Further study is warranted. Updated data to be presented. Funding: Study 204691 (NCT02723955) funded by GlaxoSmithKline in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA. Clinical trial information: NCT02723955.

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