Response to high-dose interleukin-2 (HD IL-2) therapy in patients with brain metastases from metastatic melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20007-e20007
Author(s):  
S. F. Powell ◽  
A. Z. Dudek
Keyword(s):  
Adverse Events ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Brain Lesion ◽  
Interleukin 2 ◽  
Stage Iv ◽  
Published Data ◽  
High Dose ◽  
Mixed Response ◽  
The Brain

e20007 Background: HD IL-2 has been shown to produce durable responses in patients with metastatic melanoma. The purpose of this study was to determine whether the University of Minnesota's outcomes were comparable to previously published data and to analyze subsets of patients to find further data on prognosis and response. Methods: A retrospective analysis was performed all adult patients with Stage IV melanoma treated with HD IL-2 from January 2000 to October 2008 at our institution. HD IL-2 was given I.V. every eight hours as a bolus over 15 minutes at a dose of 600,000 IU/kg. A maximum of 14 doses for each course was given. Results: A total of 15 patients with metastatic melanoma had been treated with HD IL-2 at our institution. Complete response (CR) was seen in 6.67% (N=1), partial response (PR) in 6.67% (N=1), mixed response (MR) in 6.67% (N=1), and stable disease (SD) in 13.33% (N=2). Average time to disease progression (TTDP) was 5.67 months in those with a PR or SD. Two patients with brain metastases had subsequently complete resolution of the brain lesions after HD IL-2 therapy. One of these patients has a CR and is disease free 34 months out from therapy. The other had PR and is currently alive with disease, but has no recurrence of the brain lesion after over 19 months. Twelve of the fifteen patients were able to receive 2 courses of therapy. On average patients tolerated 10.5 HD IL-2 doses with the first course and 8.8 doses with the second course. Common grade (G) 3 and 4 adverse events included hyperbilirubinemia (G 3 = 26.67%), hypotension (G 3 = 6.67%, G 4 = 6.67%), peripheral edema (G 3 = 26.67%), pulmonary edema (G 3 = 13.33%), and hypophosphatemia (G 3 = 6.67%, G 4 = 6.67%). Conclusions: The CR rate of 6.67% and TTDP in those with SD or a PR are comparable to previously published studies. Observed adverse events were also similar to other reports. HD IL-2 has typically been avoided in patients with brain metastases due to concern for neurologic complications from the capillary leak syndrome caused by treatment. We propose further evaluation of this ineligibility for HD IL-2, since carefully selected patients with brain metastases may derive benefit from this treatment. No significant financial relationships to disclose.

Gamma surgery for melanoma metastases in the brain

2002 ◽  
Vol 96 (3) ◽  
pp. 544-551 ◽  
Author(s):  
Vincenzo Mingione ◽  
Marcelo Oliveira ◽  
Dheerendra Prasad ◽  
Melita Steiner ◽  
Ladislau Steiner
Keyword(s):  
Brain Metastases ◽  
Survival Time ◽  
Cox Regression ◽  
Brain Lesion ◽  
High Dose ◽  
Content Type ◽  
Melanoma Metastases ◽  
The Brain ◽  
Fine Print

Object. The aim of this study was to evaluate the usefulness and limitations of gamma surgery (GS) in the treatment of brain metastases from melanoma. Methods. Imaging and clinical outcomes in 45 patients treated for 92 brain metastases from melanoma between October 1989 and October 1999 were retrospectively analyzed. Follow-up imaging studies were available in 35 patients with 66 treated lesions. Twenty-four percent of the lesions disappeared, 35% shrank, 23% remained unchanged, and 18% increased in size. No undue radiation-induced changes were observed in the surrounding brain. Clinical data were available in all patients. No deaths or neurological morbidity related to GS was observed. The median survival time, calculated using the Kaplan—Meier method, was 10.4 months from the time of GS. In both univariate and multivariate Cox regression analyses, a single brain lesion and lack of visceral metastases were statistically predictive of a better prognosis. Six of eight patients with solitary metastasis (that is, a single brain metastasis with no primary visceral tumor) were still alive at the close of the study, none of them with disease progression, with a follow-up period ranging between 14 and 82 months. Sixteen patients in this series received adjunctive whole-brain radiation therapy, which had no impact on their survival time or local and distant control of the brain disease. Conclusions. Gamma surgery is effective in treating melanoma metastases in the brain. It appears that the radiobiology of a single high dose overcomes the radioresistance barrier, yielding better results than fractionated radiation.

High Dose Systemic Interleukin-2 for Metastatic Melanoma in Patients with Treated Brain Metastases

2004 ◽  
Vol 27 (6) ◽  
pp. S15
Author(s):  
Richard Lochhead ◽  
Guy McKhann ◽  
Todd Hankinson ◽  
Steven Isaacson ◽  
Charles Hesdorffer ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
High Dose

scholarly journals IMMU-04. IMMUNE-RELATED ADVERSE EVENTS STRONGLY PREDICT SUPERIOR OUTCOMES IN BRAIN METASTASES PATIENTS RECEIVING LOCAL TREATMENT AND IMMUNE CHECKPOINT INHIBITORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii105-ii105
Author(s):  
Alexander Hulsbergen ◽  
Asad Lak ◽  
Yu Tung Lo ◽  
Nayan Lamba ◽  
Steven Nagtegaal ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Sensitivity Analyses ◽  
Immortal Time Bias ◽  
The Brain

Abstract INTRODUCTION In several cancers treated with immune checkpoint inhibitors (ICIs), a remarkable association between the occurrence of immune-related adverse events (irAEs) and superior oncological outcomes has been reported. This effect has hitherto not been reported in the brain. This study aimed to investigate the relation between irAEs and outcomes in brain metastases (BM) patients treated with both local treatment to the brain (LT; i.e. surgery and/or radiation) and ICIs. METHODS This study is a retrospective cohort analysis of patients treated for non-small cell lung cancer (NSCLC) BMs in a tertiary institution in Boston, MA. Outcomes of interest were overall survival (OS) and intracranial progression-free survival (IC-PFS), measured from the time of LT. Sensitivity analyses were performed to account for immortal time bias (i.e., patients who live longer receive more cycles of ICIs and thus have more opportunity to develop an irAE). RESULTS A total of 184 patients were included; 62 (33.7%) were treated with neurosurgical resection and 122 (66.3%) with upfront brain radiation. irAEs occurred in 62 patients (33.7%). After adjusting for lung-Graded Prognostic Assessment, type of LT, type of ICI, newly diagnosed vs. recurrent BM, BM size and number, targetable mutations, and smoking status, irAEs were strongly associated with better OS (HR 0.33, 95% CI 0.19 – 0.58, p < 0.0001) and IC-PFS (HR 0.41; 95% CI 0.26 – 0.65; p = 0.0001). Landmark analysis including only patients who received more than 3 cycles of ICI (n = 133) demonstrated similar results for OS and IC-PFS, as did sensitivity analysis adjusting for the number of cycles administered (HR range 0.36 – 0.51, all p-values < 0.02). CONCLUSIONS After adjusting for known prognostic factors, irAEs strongly predict superior outcomes after LT in NSCLC BM patients. Sensitivity analysis suggests that this is unlikely due to immortal time bias.

scholarly journals Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

Complete regression of subcutaneous and cutaneous metastatic melanoma with high-dose intralesional interleukin 2 in combination with topical imiquimod and retinoid cream

2011 ◽  
Vol 21 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Miki Shirakawa Garcia ◽  
Yoko Ono ◽  
Steve R. Martinez ◽  
Steven L. Chen ◽  
Heidi Goodarzi ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
High Dose ◽  
Complete Regression ◽  
Topical Imiquimod

scholarly journals The Outcomes of Nivolumab Fixed Dose 40 Mg Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Liudmila Fedorova ◽  
Kirill Lepik ◽  
Polina Kotselyabina ◽  
Elena Kondakova ◽  
Yuri Zalyalov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Median Number ◽  
Fixed Dose ◽  
Published Data ◽  
High Dose ◽  
Efficacy And Safety ◽  
Classical Hodgkin Lymphoma ◽  
Grade 3

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease progression (PD) at the moment of nivolumab initiation. B-symptoms were present in 23 pts (55%), ECOG status was grade 0-I in 25 pts (59,5%), grade II in 12 pts (29%), grade III in 4 pts (9,5%) and grade IV in 1 pt (2%). The primary endpoint was the overall response rate (ORR) determined by positron-emission tomography/computed tomography (PET/CT) using LYRIC criteria every 3 months. Key secondary endpoints included progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were evaluated according to CTCAE 4.03. The patient group characteristics were evaluated using descriptive statistics methods, the survival analysis was performed using Kaplan-Meyer method (SPSS Statistics v.17). Results The median number of nivolumab cycles was 24 (2-38). The response was evaluated in 41 out of 42 pts. The ORR was 66%. The best response included complete response (CR) in 39%, PR in 27%, stable disease in 5%, PD in 2%, indeterminate response (IR) in 27% of pts. With a median follow-up of 27,5 mo (11,3-34,5) 41 pts (97,6%) were alive, the median OS was not reached. The 2-year PFS was 44,5% (95% CI, 28,2-59,6) The nivolumab therapy was discontinued in 39 pts (93%) due to scheduled discontinuation in 14 pts (33%), PD in 13 pts (31%), grade 3-4 AE in 2 pts (5%), change of therapy because of insufficient response in 6 pts (14%) and other reasons in 4 pts (10%). The progression of disease during nivolumab therapy was present in 14 (33%) pts and after nivolumab discontinuation in 6 (14%) pts. After disease progression 30 pts (71%) were retreated with nivolumab monotherapy or in combination with chemotherapy. The median time to additional therapy was 14,5 mo (4,2 -32,9). The adverse events of any severity were observed in 30 pts (71%). Grade 3 or higher AE were present in 4 pts (9,5%), including grade 3 arthralgia, grade 3 anemia, grade 4 pneumonia and pneumonitis, grade 4 increased level of alanine aminotransferase and grade 5 MDS in 1 pt. A significant reduction of PD1+CD3+ cell population of peripheral blood lymphocytes was observed after first nivolumab cycle (median 0.7% (0-1.7) versus 33% (15.7-80.1) before therapy initiation, p = 0.02, Wilcoxon signed-rank test). Conclusion Our study demonstrated the efficacy and safety of nivolumab 40 mg therapy. The presented results are comparable to previously published data of nivolumab 3 mg/kg therapy in patients with r/r cHL. Thus, this creates a basis for further direct comparative study of nivolumab efficacy in different doses Disclosures No relevant conflicts of interest to declare.

Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study.

1991 ◽  
Vol 9 (10) ◽  
pp. 1821-1830 ◽  
Author(s):  
P A Demchak ◽  
J W Mier ◽  
N J Robert ◽  
K O'Brien ◽  
J A Gould ◽  
...  
Keyword(s):  
Pilot Study ◽  
Metastatic Melanoma ◽  
Response Rate ◽  
Tumor Regression ◽  
Interleukin 2 ◽  
Tumor Burden ◽  
High Dose ◽  
Minor Response ◽  
Exact Test ◽  
Combined Immunotherapy

In this pilot study of metastatic melanoma, interleukin-2 (IL-2) and cisplatin (CDDP) chemotherapy were combined using an alternating schedule designed to explore potential synergism between these modalities. Bolus IL-2 was given at a dose of 600,000 IU/kg intravenously (IV) every 8 hours, days 1 to 5 and 15 to 19, followed by high-dose CDDP administered by two different regimens: (A) 135 to 150 mg/m2 IV bolus over 30 minutes with the chemoprotectant WR-2721 910 mg/m2 or (B) 50 mg/m2 IV over 2 hours every day for 3 days. The trial design allowed an assessment of response to each phase of therapy. Among 27 assessable patients, there were 10 (37%) overall responses, including three (11%) complete responses (CRs) with durations of 9, 16, and 30+ months. Tumor regression was noted in seven patients (partial response [PR], four; minor response [MR], three; response rate [RR], four of 27 [15%]) after IL-2 administration and in 14 patients (PR, 12; MR, two; RR, 12 of 27 [44%]) after CDDP treatment, demonstrating noncrossresistance between the components of the regimen. Major PRs (greater than 90% reduction of tumor burden) or CRs were only seen in patients responding to IL-2. Toxicity during IL-2 therapy was typical for high-dose IL-2 protocols and was reversible. Among the first 20 patients treated with CDDP regimen A, there were eight episodes of grade IV nephrotoxicity (creatinine level greater than 5.0 mg/dL), including three of six patients treated with an initial CDDP dose of 135 mg/m2. This side effect was more frequent among patients with liver metastasis (P less than .05, Fisher's exact test). No significant nephrotoxicity was noted in seven patients treated on regimen B. Although ototoxicity was frequent, minimal bone marrow and neurologic toxicity was noted. There were no treatment-related deaths. This combination showed at least additive activity against melanoma, and the more protracted CDDP schedule was well tolerated. This regimen may serve as a model for future combined immunotherapy and chemotherapy trials in metastatic melanoma.

scholarly journals P14.85 Brain metastasis from Hodgkin’s Lymphoma: case report and literature review

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii87-iii88
Author(s):  
F Bruno ◽  
E Pronello ◽  
S Bortolani ◽  
R Palmiero ◽  
A Melcarne ◽  
...  
Keyword(s):  
Case Report ◽  
Complete Remission ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Hodgkin’S Lymphoma ◽  
Brain Lesion ◽  
Whole Brain Radiotherapy ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Thoracic Pain

Abstract BACKGROUND Central nervous system (CNS) metastases from Hodgkin’s Lymphoma (HL) are very rare, occurring in 0.02–0.5% of cases. They are usually associated to systemic relapse of the disease. Treatment options for HL brain metastases include surgery, radiotherapy, and systemic chemotherapy. CASE REPORT A 54 year-old woman presented with thoracic pain and dyspnea. Chest CT showed a thoracic bulky mass larger than 10 cm. Biopsy confirmed HL stage IIA, nodular sclerosing variant. No typical B symptoms, such as fever, night sweats or weight loss, were observed. The patient underwent chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD scheme), followed by 30Gy mediastinic radiotherapy (RT), which led to complete remission in September 2017. After 3 months, she presented with headache and rapidly progressing gait disorder. MRI showed a contrast-enhanced lesion in the right occipital lobe, with central necrosis and massive edema. Total-body CT scan and FDG-PET ruled out either the presence of new solid tumors or systemic relapses of HL. Gross total resection of the brain lesion was carried out, and HL histology was confirmed. CSF analysis from lumbar puncture was normal. Afterwards, the patient underwent 2 cycles of high dose cytarabine, but she rapidly progressed, and received salvage RT (30 Gy). Nevertheless, further systemic progression occurred: the patient developed headache, diplopia and dysphagia and, unfortunately, she died 6 months after the diagnosis of brain metastasis. DISCUSSION Thus far, only 45 cases of CNS HL have been reported from 2000 to 2018. Whole brain radiotherapy, with or without chemotherapy, was the most common treatment. In our patient, we chose surgical resection for the solitary brain metastasis followed by chemotherapy, delaying RT at recurrence. In the literature, median overall survival of patients diagnosed with brain metastases from HL is 18 months (1–273): 17 patients (38%) showed a progression (local / systemic: 12/17 - 71%), while 28 (62%) showed complete remission after a median follow-up of 20 months (6–273). CONCLUSION Intracranial localisation of Hodgkin’s Lymphoma is a rare entity but still has to be taken into account. Advanced brain imaging could be of help in case of uncertain radiological presentation. A multidisciplinary approach is needed as there is no consensus on the best treatment to choose: surgery, radiotherapy and chemotherapy should be considered on individual basis.

Management of Metastatic Melanoma to the Breast with High-Dose Interleukin-2 and Surgical Resection

2005 ◽  
Vol 11 (2) ◽  
pp. 158-159 ◽  
Author(s):  
Ian K. Komenaka ◽  
Gail DeRaffele ◽  
Karl S. Hurst-Wicker ◽  
Howard L. Kaufman
Keyword(s):  
Metastatic Melanoma ◽  
Surgical Resection ◽  
Interleukin 2 ◽  
High Dose
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