Efficacy of ipilimumab after anti-PD-1 therapy in sequential treatment of metastatic melanoma patients - Real world evidence

Cybulska-Stopa, Bożena; Rogala, Paweł; Czarnecka, Anna; Ługowska, Iwona; Teterycz, Paweł; Galus, Łukasz; Rajczykowski, Marcin; Dawidowska, Anna; Piejko, Karolina; Suwiński, Rafał; Mackiewicz, Jacek; Rutkowski, Piotr

doi:10.1016/j.advms.2020.05.005

Cited by 14 publications

(8 citation statements)

References 33 publications

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“…Since the introduction of anti–PD-1 antibodies, which have shown superior first-line efficacy compared with ipilimumab [ 14 , 15 ], ipilimumab has been less commonly used as first-line monotherapy. However, it is still used in combination with nivolumab as first-line therapy in patients with advanced melanoma [ 14 ] and as subsequent therapy in patients with disease progression after single-agent anti–PD-1 treatment [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

et al. 2021

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Background Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. Methods IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. Results Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti–programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab–treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab–treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. Conclusions With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. Trial registration ClinicalTrials.gov, NCT01511913. Registered January 19, 2012 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913

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Section: Introductionmentioning

confidence: 99%

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

et al. 2021

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“…Differences in ORR were seen depending on prior therapies, although none of them with significant differences, such as prior anti–CTLA-4 (yes: ORR 32.8% vs. no: 25%) and prior anti–CTLA-4/anti–PD-1 combination therapy (yes: ORR 26.8% vs. no: 36.6%). Despite varying response rates, with lower ORRs reached in more heavily pretreated patients, these results show that TIL therapy remains a treatment option in patients who have exhausted all previously approved treatment possibilities, such as immune checkpoint inhibitors (as single agent or anti-CTLA-4/anti-PD-1 combination therapy) and targeted therapies 40,44,45 . Therefore, these trials demonstrate that TIL therapy is an effective treatment option in the current melanoma treatment landscape.…”

Section: Tumor-infiltrating Lymphocyte Therapymentioning

confidence: 80%

“…Despite varying response rates, with lower ORRs reached in more heavily pretreated patients, these results show that TIL therapy remains a treatment option in patients who have exhausted all previously approved treatment possibilities, such as immune checkpoint inhibitors (as single agent or anti-CTLA-4/anti-PD-1 combination therapy) and targeted therapies. 40,44,45 Therefore, these trials demonstrate that TIL therapy is an effective treatment option in the current melanoma treatment landscape. Currently, the application of TIL therapy as a first-line treatment in previously untreated melanoma patients is being investigated as well (NCT05727904).…”

Section: History Of Clinical Developmentmentioning

confidence: 97%

Tumor-Infiltrating Lymphocyte and Other Cell Therapies for Metastatic Melanoma

Los,

Klobuch,

Haanen

2024

Cancer J

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Major progress in prolonging survival of patients with advanced melanoma has been made in the past decade because of the development and approval of immune checkpoint inhibitor and targeted therapies. However, for nonresponding or relapsing patients, their prognosis is still dismal. Based on clinical trial data, treatment with adoptive cell therapies holds great promise. In patients with metastatic melanoma progressing on or nonresponsive to single-agent anti–programmed cell death 1, infusion of tumor-infiltrating lymphocytes can produce responses in up to half of patients, with durable complete responses in up to 20%. Genetic modification of peripheral blood T cells with T-cell receptors derived from tumor-specific T cells, or with chimeric antigen receptors, has the potential to further improve treatment outcomes in this refractory population. In this review, we will discuss the historical development, current status, and future perspectives of adoptive T-cell therapies in melanoma.

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“…17 Retreatment with ICI is a common practice, despite the lack of Food and Drug Administration approval in this setting and the general recommendation by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) to switch classes of agents and to consider treatments with a different mechanism of action (MOA) from previous therapies that were not efficacious. 18 Reuse of ICI by treatment with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic lymphocyte-associated protein 4 (CTLA-4) after prior ICI failure has yielded response rates ranging from 8% to 29%, [19][20][21][22][23][24] OS of 5-26 months, 19-22 24 25 progression-free survival (PFS) of 3-5 months, [19][20][21][22] and limited durations of response (DORs) in early-line and later-line patients [20][21][22] ; similarly, the newer anti-lymphocyte activation gene 3 (LAG-3) and anti-PD-1 combination has also shown a modest response rate of 11.5% in the later setting. 26 The recurrence of irAEs following rechallenge with ICI is also a concern 27 28 ; in an analysis of patients restarting anti-PD-1 after experiencing severe irAEs on anti-PD-1 plus anti-CTLA-4 therapy, irAEs (any grade) were reported in 50% of the patients, and 30% discontinued treatment due to these AEs.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study

Chesney

Lewis

Kluger

et al. 2022

J Immunother Cancer

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BackgroundPatients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.MethodsEligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1).ResultsThe Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%).ConclusionsInvestigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease.

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Efficacy of ipilimumab after anti-PD-1 therapy in sequential treatment of metastatic melanoma patients - Real world evidence

Cited by 14 publications

References 33 publications

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

Tumor-Infiltrating Lymphocyte and Other Cell Therapies for Metastatic Melanoma

Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study

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