scholarly journals Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis

2016 ◽  
pp. bcr2016216426 ◽  
Author(s):  
Rubens Chang ◽  
Keisuke Shirai
Keyword(s):  
Advanced Melanoma ◽  
Safety And Efficacy

scholarly journals P865 Safety & efficacy of lifileucel (LN-144) tumor infiltrating lymphocyte therapy in metastatic melanoma patients after progression on multiple therapies – independent review committee data update

2020 ◽  
Vol 8 (Suppl 1) ◽  
pp. A12-A12
Author(s):  
Amod Sarnaik ◽  
Nikhil Khushalani ◽  
Jason Chesney ◽  
Harriet Kluger ◽  
Brendan Curti ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Advanced Melanoma ◽  
Review Committee ◽  
Safety And Efficacy ◽  
Mek Inhibitors ◽  
Tumor Infiltrating Lymphocyte ◽  
Heavily Pretreated ◽  
Independent Review ◽  
Melanoma Patients

BackgroundTreatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel, a centrally manufactured cryopreserved autologous TIL therapy assessed by both investigator and an independent review committee (IRC), are presented.MethodsC-144-01 is a global Phase 2 open-label, multicenter study of the safety and efficacy of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 66) patients with Stage IIIC/IV unresectable melanoma who received lifileucel. Tumors resected at local institutions were processed in central GMP facilities for TIL production in a 22-day process. Final TIL infusion product was cryopreserved and shipped to sites. Patients received one week of cyclophosphamide/fludarabine preconditioning lymphodepletion, a single lifileucel infusion, followed by up to 6 doses of IL-2. All responses were assessed by RECIST 1.1.Results66 patients had the following baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), relatively high tumor burden (106 mm mean target lesion sum of diameters), 44% with liver and/or brain lesions, median LDH 244 U/L. Objective Response Rate (ORR) by investigator was 36.4% (2 CR, 22 PR, 1 previously confirmed PR is now changed to SD) and Disease Control Rate (DCR) of 80.3%. At a median follow up of 9.7 months, median Duration of Response (DOR) has not been reached. The adverse event profile was generally consistent with the underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens.The ORR per IRC was 34.8% (2 CR, 21 PR) and DCR was 72.7%. At a median follow up of 6.9 months, the median IRC DOR has not been reached. Overall concordance rate of investigator and IRC read of response was 89.4%. The concordance compares favorably with literature reports in a metastatic disease.1ConclusionsLifileucel treatment resulted in a 36.4% ORR in heavily pretreated metastatic melanoma patients with high baseline disease burden who had received prior anti-PD1 and BRAF/MEK inhibitors, if tumor BRAF mutated. The high concordance of 89.4% between investigator and IRC confirms the original assessment of lifileucel efficacy in metastatic melanoma.2AcknowledgementsThe authors would like to thank the patients and their families for participation in the study.The authors would also like to acknowledge the support and dedication of all investigators and site team members from all participating clinical trial institutions.Trial RegistrationClinicalTrials. gov Identifier: NCT02360579Ethics ApprovalEthics Approval This trial was approved by Western Institutional Review Board - IRB Tracking Number: 20160198.ReferencesGhiorghiu DC, et al. Comparison of central and site review of RECIST data in an open randomised phase II trial in advanced melanoma. 10.1594.ecr 2009/C-075.Sarnaik A, et al. Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1. J Clin Oncol 2019;37:2518–2518.

scholarly journals Safety and Efficacy of Ipilimumab 10 Mg/Kg Among Patients with Advanced Melanoma from Italy Enrolled in a European Compassionate Use Program

2012 ◽  
Vol 23 ◽  
pp. ix373-ix374
Author(s):  
M. Maio ◽  
P. Queirolo ◽  
A. Testori ◽  
M. Altomonte ◽  
M. Maur ◽  
...  
Keyword(s):  
Advanced Melanoma ◽  
Compassionate Use ◽  
Safety And Efficacy

scholarly journals Retrospective analysis of safety and efficacy of anti-PD-1 therapy and radiation therapy in advanced melanoma: A bi-institutional study

2019 ◽  
Vol 138 ◽  
pp. 114-120 ◽  
Author(s):  
Yvonne M. Mowery ◽  
Kirtesh Patel ◽  
Mudit Chowdhary ◽  
Christel N. Rushing ◽  
Kingshuk Roy Choudhury ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Retrospective Analysis ◽  
Advanced Melanoma ◽  
Safety And Efficacy

Combination anti-PD-1 and ipilimumab (ipi) therapy in patients with advanced melanoma and pre-existing autoimmune disorders (AD).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10026-10026
Author(s):  
Lauren Julia Brown ◽  
Alison Weppler ◽  
Prachi Bhave ◽  
Clara Allayous ◽  
James Randall Patrinely ◽  
...  
Keyword(s):  
Single Agent ◽  
Advanced Melanoma ◽  
Duodenal Perforation ◽  
P Value ◽  
Efficacy And Safety ◽  
Safety And Efficacy ◽  
Toxicity Risk ◽  
Substantial Risk ◽  
Inflammatory Bowel

10026 Background: Clinical trials of immunotherapy exclude patients (pts) with pre-existing AD. While retrospective data exist regarding the efficacy and safety of single agent ipi and anti-PD1 antibodies (PD1) in pts with AD, no data are available regarding the safety and efficacy of combination therapy in pts with AD, which has a higher toxicity risk. Methods: Pts with melanoma and pre-existing AD treated with combination ipi/PD1 were retrospectively identified from 10 international centres. Data regarding AD, treatment, toxicity and outcomes were examined. Results: Fifty-five pts were included, 46 were treated with ipi/nivolumab and 9 with ipi/pembrolizumab. 40 had an ipi dose of 3mg/kg while 15 had a lower dose regimen. 9 pts received prior PD1 therapy; 3 suffered moderate immune-related adverse events (irAE) with no flares of AD on single agent PD1. Pre-existing AD included inflammatory bowel disease (IBD), thyroiditis, rheumatoid arthritis (RA), multiple sclerosis and psoriasis. 10 pts had active symptoms of AD and 13 were immunosuppressed at commencement of ipi/PD1. Eighteen pts (33%) experienced a flare of their AD including 4/7 with RA, 3/6 with psoriasis, 5/9 with IBD, 3/18 with thyroiditis, 1/1 with Sjogren’s syndrome, 1/1 with polymyalgia, 1/1 with Behcet’s syndrome. Median time to flare was 19 days (range 4 – 167). 13 pts were managed with steroids, 5 required additional immunosuppressants. 7 pts were hospitalised for management of flare (5 with IBD, 2 with RA). 2 pts required intensive care and vasopressors for severe IBD flare, quiescent prior to ipi/PD1. One for diarrhoea and shock and one for duodenal perforation. 8 pts ceased treatment due to flare (3 with IBD, 2 with RA, 1 with Behcet’s, 1 with Sjogren’s). Thirty-seven pts (67%), experienced an irAE unrelated to their AD, 38% G3 or G4. The most frequent irAEs were colitis (n = 16), hepatitis (n = 12), endocrinopathies (n = 12), with 13 pts experiencing an irAE in ≥ 2 organs. 9 pts experienced both AD flare and an irAE. 20 pts (36%) ceased immunotherapy due to irAEs. ORR was 55% (54% in PD1 naive pts), at a median follow up of 14 months, 77% of responses ongoing. ORR in pts who had a flare of their AD was 44% and in pts on immunosuppression was 46%. Median PFS was shorter in pts who had a flare of AD compared with those who did not (2.6 vs 9 months; P-value 0.047). Conclusions: Combination ipi/PD1 shows efficacy comparable to clinical trial populations in pts with pre-existing AD and advanced melanoma. Whilst there was a substantial risk of flare of AD, no increased frequency of irAE’s was observed.

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab

2016 ◽  
Vol 96 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Rosie Qin ◽  
Adam Olson ◽  
Bhavana Singh ◽  
Samantha Thomas ◽  
Steven Wolf ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Advanced Melanoma ◽  
Safety And Efficacy ◽  
Melanoma Patients

Safety and efficacy of lifileucel (LN-144), an autologous, tumor infiltrating lymphocyte cell therapy in combination with pembrolizumab for immune checkpoint inhibitor naïve patients with advanced melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9537-9537
Author(s):  
Sajeve Samuel Thomas ◽  
Gino Kim In ◽  
Bernard Doger ◽  
Simon Haefliger ◽  
Juan Martin-Liberal ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Advanced Melanoma ◽  
Autologous Tumor ◽  
Open Label ◽  
Safety And Efficacy ◽  
Tumor Infiltrating Lymphocyte

9537 Background: Tumor infiltrating lymphocyte (TIL) cell therapy has demonstrated safety and efficacy in advanced melanoma, both in the pre-immune checkpoint inhibitor (ICI) setting (Goff, JCO 2016) and in patients who have failed anti-PD-1/PD-L1 therapy (Sarnaik, 2020). Combination of TIL and pembrolizumab (pembro) in ICI-naïve patients has demonstrated encouraging efficacy data with acceptable safety in head and neck squamous cell carcinoma (Jimeno, 2020). To improve treatment options in early lines, we explore a combination of LN-144 and pembro in patients with ICI-naïve advanced melanoma. Methods: IOV-COM-202 is a Phase 2 multicenter, multi-cohort, open-label study evaluating TIL cell therapy in multiple settings and indications. We report on Cohort 1A enrolling ICI-naïve advanced melanoma (unresectable or metastatic) patients for treatment with a combination of LN-144 and pembro. Key eligibility criteria include ≤ 3 lines of prior therapy, ECOG < 2, one resectable lesion for lifileucel manufacturing, and ≥ 1 measurable lesion for response assessment. Primary endpoints are objective response rate (ORR) per RECIST 1.1 and safety as measured by incidence of Grade ≥3 treatment-emergent adverse events (TEAE). LN-144 is generated at centralized GMP facilities in a 22-day process. A nonmyeloablative lymphodepletion (NMA-LD) using cyclophosphamide and fludarabine is administered preceding a single LN-144 infusion, followed by < 6 doses of IL-2 (600,000 IU/kg). Pembro is administered after tumor harvest but prior to NMA-LD and continues after lifileucel per label. Results: Seven patients have received lifileucel in combination with pembro as of data extraction date (Feb 14, 2021). Five of the 7 treated patients were treatment-naïve, 1 patient had prior BRAFi + MEKi and 1 had received prior chemotherapy; 71% had liver/brain lesions, 43% had LDH > ULN. Mean SOD for the target lesions was 111 mm, with 86% of patients with > 3 target lesions, representing advanced disease at baseline for this patient group. The TEAE profile was consistent with the underlying disease and known AE profiles of pembro, NMA-LD and IL-2. Six patients had a confirmed objective response with an ORR of 86% (1 CR, 5 PR) and 1 best response of SD. Three of the responding patients have remained off pembro due to pembro related AEs for 3, 4 and 13 months (mos), yet maintaining response. All responding patients remain in response with the longest duration of response being 16.8 mos. Conclusions: Lifileucel can be safely combined with pembro in patients with ICI-naïve advanced melanoma. The ORR of 86% is encouraging when compared to pembro alone in a similar patient population, especially considering the disease burden at baseline and persistence of responses in patients off therapy. Enrollment is ongoing and updated data to be presented. Clinical trial information: NCT03645928.

Retrospective analysis of safety and efficacy of ipilimumab in elderly patients with advanced melanoma.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 9540-9540 ◽  
Author(s):  
Andrew Cota Shaw ◽  
VanAnh Trinh ◽  
Roland L. Bassett ◽  
Isabella Claudia Glitza ◽  
Adi Diab ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Retrospective Analysis ◽  
Advanced Melanoma ◽  
Safety And Efficacy
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