scholarly journals Retrospective Analysis of Rechallenge with Ipilimumab in Patients with Metastatic Melanoma

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
A. A. Formozo ◽  
J. R. Gomes ◽  
R. A. Schmerling ◽  
A. C. Buzaid
Keyword(s):  
Metastatic Melanoma ◽  
Retrospective Analysis ◽  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Significant Benefit ◽  
Limited Data ◽  
Free Survival ◽  
Median Progression Free Survival

Background. Checkpoint inhibitors are effective in the treatment of several types of cancer, either being used separately or in combination. Ipilimumab pioneered the treatment of metastatic melanoma, and nowadays, it has been used more frequently in combination with anti-PD-1. Since the development of anti-PD1 for melanoma, rechallenge with ipilimumab has not been considered, although its use was considered in early trials. Cases. In this study, we analyzed 22 patients with metastatic melanoma who had benefited from the first treatment with ipilimumab, but eventually had progressive disease. They received ipilimumab at the same dose as the first treatment. Most of the patients received the second course after six months or more from the first treatment with ipilimumab. The median progression-free survival (mPFS) of the treatment with ipilimumab was 8.9 months, and the median progression-free survival of the second course was 6.3 months. Conclusion. There are limited data on rechallenge with ipilimumab addressing progression-free survival (PFS). In our analysis, twenty-two patients treated with a second course of ipilimumab were analyzed and most of them had a significant benefit. Despite the current alternatives for salvage therapies, rechallenging with ipilimumab might be an alternative to be considered in patients who had initial benefit.

scholarly journals Prognostic implications of PD-L1 expression in patients with angiosarcoma

2021 ◽  
pp. FSO691
Author(s):  
Jii Bum Lee ◽  
Beung-Chul Ahn ◽  
Seung Hyun Kim ◽  
Young Han Lee ◽  
Jung Woo Han ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Prognostic Biomarker ◽  
Progression Free Survival ◽  
Limited Data ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Median Progression Free Survival ◽  
Programmed Death ◽  
Prognostic Implications

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients.

scholarly journals Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group

2008 ◽  
Vol 26 (35) ◽  
pp. 5748-5754 ◽  
Author(s):  
Michael B. Atkins ◽  
Jessie Hsu ◽  
Sandra Lee ◽  
Gary I. Cohen ◽  
Lawrence E. Flaherty ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Response Rates ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Median Progression Free Survival

Purpose Phase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, a phase III trial was performed within the United States Intergroup. Patients and Methods Patients were randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. Tumor response was assessed after cycles 2 and 4, then every 3 months. Results Four hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001). Conclusion Although BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma.

Pilot Evaluation of the Value of FDG PET-CT after One and Two Cycles of Salvage Chemotherapy in Relapsed/Refractory Aggressive Non-Hodgkin’s and Hodgkin’s Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4951-4951
Author(s):  
Andrew Hodson ◽  
Tara Barwick ◽  
Brigitta Marson ◽  
Nick Maisey ◽  
Kavita Raj ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Dose Escalation ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Pet Ct ◽  
Risk Of Relapse

Abstract Introduction The currently accepted standard of care for patients with relapse/refractory NHL is dose escalation and consolidation with Stem Cell Transplantation. The ability to predict those patients who may benefit or not from this approach would be beneficial. Whole-body Positron Emission Tomography using 18F-fluorodeoxyglucose (FDG) is now recognised to have predictive ability in those patients at high risk of relapse and shortened overall survival in De novo High grade lymphoma. In the salvage setting it is unknown whether the appearance of PET scan after 1 cycle of salvage treatment may predict similarly for outcome post transplant and whether early scanning is indicated before cycle 2 salvage chemotherapy. Aim: The aim of this study is to assess whether the PET-CT after one cycle or two cycles of dose escalation was predictive of outcome in patients with relapse/refractory NHL. Methods: We collected the data prospectively of all patients with relapsed or refractory aggressive NHL or HD treated in our institution over a 2 year period who were considered suitable for salvage therapy followed by Stem Cell Transplantation. We identified 14 male and 10 female patients with a mean age of 44 years (range 24–66). 12 patients had disease refractory to first line treatment and 12 patients had relapsed disease with a median interval from completion of treatment to relapse of 20 months (range 2–60). All patients were initially treated with DHAP as salvage therapy.22/24 patients proceeded to a stem cell transplant. 16/22 had an autologous transplant conditioned with BEAM and 6/22 had allogeneic transplants.FDG PET- CT scans were performed (all positive) prior to salvage chemotherapy and then assessed after 1 cycle of salvage chemotherapy and then after the second cycle using a 5 point visual scoring system as follows: CMR - no uptake at disease sites, MRU1 – visually uptake below level of mediastinum, MRU2 – visually between mediastinum and liver Stable/persistent metabolically active disease and Progressive disease (either new lesions or increased uptake in the same sites. Results FDG-PET Data was collected from 24 patients (14 male and 10 female) and read by two independent observers. The patients had the distribution shown in table: Visual response criteria Appearance PET 1 : Patient Numbers Appearance PET 2 : Patient Numbers CMR 1 6 MRU1 0 2 MRU2 1 3 Stable/persistent 16 5 Progressive 6 8 The median progression free survival of the patients with progression after one cycle of chemotherapy was 1.5 months with 3/6 deaths. Progression on PET1 was seen only in refractory cases pre salvage and was associated with a significant risk of relapse (p=0.014). The median progression free survival of the patients with stable disease after one cycle was 9.5 months. After two cycles of chemotherapy the median progression free survival of patients with CMR/MRU1/MRU2 was 9 months, compared with stable disease of 8 months and progressive disease 6 months. Conclusions: Patients with progressive disease on PET after one cycle of chemotherapy have a poor outcome with 50% early deaths and would be candidates for targeted/experimental therapies. Longer follow up will be required to assess the significance of stable or persistent disease on PET after one cycle and two cycles of salvage chemotherapy.

Angiogenic and immunomodulatory biomarkers in axitinib-treated patients (pts) with advanced renal cell carcinoma (aRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 614-614 ◽  
Author(s):  
Brian I. Rini ◽  
Bernard Escudier ◽  
Danielle Murphy ◽  
Panpan Wang ◽  
Jamal Christo Tarazi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Outcomes ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Kaplan Meier ◽  
Clinical Trial Information

614 Background: Axitinib (axi) is approved for 2nd-line treatment of aRCC. In AXIS trial, median progression-free survival (PFS) was significantly longer in axi- vs sorafenib (sor)-treated pts (hazard ratio [HR] 0.67, 95% CI 0.54–0.81, P<0.0001). Association between mRNA/miRNA expression and clinical outcomes in a subset of axi- or sor-treated pts from AXIS was assessed. Methods: mRNA/miRNA analyses were performed on archival tumor samples. Expression was summarized for responders (complete and partial response) vs non-responders (stable and progressive disease), and for maximum percent tumor change. PFS and overall survival (OS) were analyzed by Kaplan-Meier. Results: Pt characteristics were similar between axi (n=34) and sor (n=33) arms. Association with outcomes is shown in the Table. A correlation was observed for CD68 protein and mRNA expression in axi-treated pts (R=0.4774 P=0.0043 and R=0.3985 P=0.0196, respectively). Both CXCR4 and TLR3 showed differences between treatment arms and association with PFS. TNFSF10 <median, and CD163, CSF1R and miR-221-5p ≥median were associated with shorter OS with axi vs sor ( P<0.05). Clinical trial information: NCT00678392. Conclusions: Immune-related biomarkers were associated with clinical outcomes in axi/sor-treated aRCC pts. Lower CCR7 expression was associated with better response and OS in axi-treated pts. CXCR4 and TLR3 may be predictive of response to axi. Analysis in a larger cohort is warranted.[Table: see text]

Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.

1998 ◽  
Vol 16 (5) ◽  
pp. 1869-1878 ◽  
Author(s):  
Y Shimizu ◽  
F Akiyama ◽  
S Umezawa ◽  
T Ishiya ◽  
K Utsugi ◽  
...  
Keyword(s):  
Median Survival ◽  
Cervical Carcinoma ◽  
Pulmonary Toxicity ◽  
Low Dose ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Reduced Toxicity ◽  
Significant Nausea

PURPOSE To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS AND METHODS Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years. Eighty-seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2 bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4 hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS All 90 patients were assessable for response, toxicity, and survival. After a median of four cycles (range, two to 10 cycles), we observed objective responses in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59, respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to 100 months). The median survival for patients who achieved CR, PR, no change (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4 months, respectively. The median progression-free survival for patients who achieved CR and PR were NR and 12.3 months, respectively. There was no significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin. The reduced toxicities allowed this regimen to be administered at the projected dose-intensities. CONCLUSION The CLD-BOMP regimen has significant antitumor activity with markedly reduced toxicity.

scholarly journals Real-World Outcomes With Generic Pomalidomide in Relapsed Refractory Multiple Myeloma—Experience From a Tertiary Care Cancer Center

2021 ◽  
pp. 361-367
Author(s):  
Suresh Kumar Bondili ◽  
Bhausaheb Bagal ◽  
Abhinav Zawar ◽  
Pradeep Ventrapati ◽  
Jayashree Thorat ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Retrospective Analysis ◽  
Tertiary Care ◽  
Progression Free Survival ◽  
Response Rates ◽  
Cancer Center ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Median Progression Free Survival

PURPOSE The prognosis of relapsed and refractory multiple myeloma (RRMM) that is refractory to bortezomib and lenalidomide is very poor wherein the median survival is between 3 and 9 months. We did this retrospective analysis to study the pattern of utilization, tolerance, and outcomes with pomalidomide in these patients having RRMM. MATERIALS AND METHODS Retrospective analysis of all the patients who were treated with generic pomalidomide at Tata Memorial Centre, Mumbai, during the period of May 2017 to March 2019 was done. Patients with secretory disease and who had completed at least one cycle of pomalidomide were analyzed for response rates, toxicity, and survival outcomes. RESULTS A total of 81 patients received pomalidomide-based therapy during this study period, out of which 75 were included in the survival analysis. Forty-eight patients (59.3%) were refractory to both lenalidomide and bortezomib. Overall response rate was 58.7%. Five patients (6.7%) achieved complete response, very good partial response was seen in 13 patients (17.3%), and partial response was seen in 26 patients (34.7%). After a median follow-up of 11 months (range 2-27 months), median progression-free survival was 9.1 months (95% CI, 5.4 to 12.9 months). Median progression-free survival for patients who were refractory to both lenalidomide and bortezomib versus nonrefractory was 5.5 and 12.6 months, respectively, which was significant statistically ( P = .04, hazard ratio, 0.35, 95% CI, 0.28 to 0.97). The median overall survival was not reached. Important toxicities included anemia (28%), neutropenia (16%), pneumonia (16%), and venous thrombosis (5%). CONCLUSION Generic pomalidomide-based therapy is an effective option and is well tolerated in patients with RRMM. Higher response rates and longer survival seen in our study are possibly because of heterogeneity of the study population.

Co-occurring alteration of NOTCH and DDR pathways serve as novel predictor to efficacious immunotherapy in NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21106-e21106
Author(s):  
Zhimin Zhang ◽  
Yanyan Gu ◽  
Xiaona Su ◽  
Jing Bai ◽  
Wei Guan ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Notch Pathway ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Free Survival ◽  
Future Clinical Practice ◽  
Cancer Genome Atlas ◽  
Nsclc Patients

e21106 Background: Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the majority produce an ultra-rapid progressive disease. Methods: Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. 106 NSCLC patients treated with immunotherapy were combined from Rizvi et. al and Hellman et. al studies (whole exon sequencing) as the discovery dataset. Two independent validation datasets were comprised of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. Results: In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [ 22.1 vs 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2-0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [ Cohort 2: 13 vs 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31-0.96 ; Cohort 3: 21 vs 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18-1.1 ]. By analyzing TCGA cohort, we found patients with coexisting NOTCH and co-DDR pathway had a higher TMB, more infiltration of CD4+T cells. Conclusions: Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.

scholarly journals Co-Occurring Alteration of NOTCH and DDR Pathways Serves as Novel Predictor to Efficacious Immunotherapy in NSCLC

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhimin Zhang ◽  
Yanyan Gu ◽  
Xiaona Su ◽  
Jing Bai ◽  
Wei Guan ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Notch Pathway ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Free Survival ◽  
Future Clinical Practice ◽  
Cancer Genome Atlas ◽  
Nsclc Patients

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 vs 3.6 months, p &lt; 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2–0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 vs 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31–0.96; Cohort 3: 21 vs 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18–1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.

Retrospective analysis of retreatment with Ipilimumab in patients with metastatic melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22032-e22032
Author(s):  
André Alexandre Formozo ◽  
Jessica Ribeiro Gomes
Keyword(s):  
Metastatic Melanoma ◽  
Clinical Benefit ◽  
Medical Literature ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Current Treatment ◽  
Retrospective Evaluation ◽  
Free Survival ◽  
Progression Of Disease ◽  
Oncology Center

e22032 Background: The checkpoint inhibitors are effective in the treatment of many types of neoplasia, either being used separately or in combination. Ipilimumab pioneered the treatment of metastatic melanoma and nowadays it has being used in combination with anti-PD1. Retreatment with Ipilimumab has rarely been reported, but it may be an important strategy for the current treatment of metastatic melanoma. In this study we analyzed the patients with metastatic melanoma who were retreated with Ipilimumab. Methods: We evaluated patients with metastatic melanoma who had benefited from the first treatment with Ipilimumab, but eventually had progression of disease. They received Ipilimumab at the same dose as the first treatment (3 mg/kg every 3 weeks for four cycles). The effect was evaluated for progression free survival and clinical benefit. Results: Twenty–two patients were retreated with Ipilimumab in our Oncology Center. Most of them retreated six months or more, after the prior treatment. The progression free survival of the first treatment with Ipilimumab was 9.9 months. The median progression free survival of the retreatment was 6.3 months. Fourteen patients were reported to have clinical benefit (63%). Conclusions: This is a retrospective evaluation about the retreatment with Ipilimumab in patients with metastatic melanoma. It has been rarely reported in the medical literature, especially Ipilimumab at doses of 3 mg/kg. Maybe the next step might be the combined retreatment with Ipilimumab and anti-PD1.

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