IPILIMUMAB IN PATIENTS WITH DISSEMINATED MELANOMA: THE N.N. PETROV NATIONAL MEDICAL RESEARCH CENTER OF ONCOLOGY EXPANDED ACCESS PROGRAM EXPERIENCE

Ipilimumab (IPI) provides a ten-year overall survival in almost 20 % of selected patients participated in several phase II-III trials. However, the expanded access program (EAP) looks more like routine practice than like clinical trials& This is why the results of such application could be different. Here we present the long-term follow-up data of single center EAP. Ninety-six patients with disseminated melanoma progressing after at least one lines of drug therapy were included at the N.N. Petrov National Medical Research Center of Oncology. Sixty-seven (70 %) patients had stage IV M1c, 35 patients (36 %) had elevated LDH before initiating IPI therapy. All patients received IPI 3 mg / kg IV every 3 weeks for a maximum of 4 cycles. Totally, 320 cycles (mean - 3.3 per patient) were conducted. Grade 3-4 immuno-mediated adverse events (imAE) observed in 18 (19 %) patients. Three patients died of adverse events, possibly associated with ongoing therapy. The median time to progression was 3 (95 % CI, 2.4 to 3.5) mo., the median overall survival was 13 (95 % CI, 8.3 to17.6) mo. Previous immunotherapy with dendritic cell vaccines decreased the risk of death by 48 % (Log-rank p = 0.049). The wild type BRAF status increased three-year overall survival from 29 to 68 % (p = 0.042). Our data confirms long-term safety and efficacy of IPI in patients with pretreated disseminated melanoma in the close to real practice setting.

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Nivolumab in never-smokers with advanced squamous non-small cell lung cancer: Results from the Italian cohort of an expanded access program

Tumor Biology ◽

10.1177/1010428318815047 ◽

2018 ◽

Vol 40 (11) ◽

pp. 101042831881504 ◽

Cited By ~ 3

Author(s):

Marina Chiara Garassino ◽

Lucio Crinò ◽

Annamaria Catino ◽

Andrea Ardizzoni ◽

Enrico Cortesi ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Expanded Access ◽

Expanded Access Program ◽

Never Smokers ◽

Access Program

Objectives: Never-smokers may be a distinct subgroup among patients with advanced non-small cell lung cancer, appearing to benefit less from immunotherapy than smokers. We report results from never-smokers enrolled in the Italian cohort of the nivolumab expanded access program in pre-treated patients with advanced squamous non-small cell lung cancer. Materials and methods: Nivolumab (3 mg/kg every 2 weeks for ≤24 months) was available on physician request. Efficacy data included objective tumor response, date of progression, and survival information. Safety was monitored. Results: Overall, 371 patients received at least one dose of nivolumab, including 31 never-smokers (8%). Objective response rate, disease-control rate, and median overall survival were 23%, 45%, and 12.1 months (95% confidence interval: 3.7–20.4), respectively, in never-smokers, and 18%, 47%, and 7.9 months (95% confidence interval: 6.2–9.6), respectively, in the overall expanded access program population. Any-grade and grade 3–4 treatment-related adverse events were reported in 12 (39%) and 3 (10%) never-smokers, respectively, and in 109 (29%) and 21 (6%) patients, respectively, in the overall expanded access program population. Grade 3–4 treatment-related adverse events in non-smokers were increased transaminases (n = 2; 6%) and diarrhea (n = 1; 3%). Treatment-related adverse events led to treatment discontinuation in 4 non-smokers (17%) and in 26 patients (9%) overall. Conclusion: Pre-treated never-smokers with advanced squamous non-small cell lung cancer in this Italian expanded access program demonstrated efficacy and safety that were consistent with those in the overall expanded access program population and clinical trials. These results suggest that a proportion of never-smoker patients with squamous non-small cell lung cancer may be responsive to immunotherapy. Other factors, such as the tumor mutational load and the status of programmed death-ligand 1, anaplastic lymphoma kinase, and epidermal growth factor receptor, might play a potential key role.

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Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP)

Annals of Oncology ◽

10.1093/annonc/mdw334.19 ◽

2016 ◽

Vol 27 ◽

pp. iv35 ◽

Cited By ~ 1

Author(s):

G. Paganelli ◽

G. Procopio ◽

M. Cabria ◽

E. Cortesi ◽

M. Tucci ◽

...

Keyword(s):

Overall Survival ◽

Expanded Access ◽

Expanded Access Program ◽

Radium 223 ◽

Access Program

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Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program

Lung Cancer ◽

10.1016/j.lungcan.2019.12.014 ◽

2020 ◽

Vol 140 ◽

pp. 59-64 ◽

Cited By ~ 8

Author(s):

Editta Baldini ◽

Alice Lunghi ◽

Enrico Cortesi ◽

Daniele Turci ◽

Diego Signorelli ◽

...

Keyword(s):

Adverse Events ◽

Clinical Outcomes ◽

Expanded Access ◽

Expanded Access Program ◽

Nsclc Patients ◽

Access Program

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Rates and Risk Factors for Adverse Events Associated with Didanosine in the Expanded Access Program

Clinical Infectious Diseases ◽

10.1093/clinids/19.6.1076 ◽

1994 ◽

Vol 19 (6) ◽

pp. 1076-1083 ◽

Cited By ~ 32

Author(s):

A. Schindzielorz ◽

I. Pike ◽

M. Daniels ◽

L. Pacelli ◽

L. Smaldone

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Expanded Access ◽

Expanded Access Program ◽

Access Program

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Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.5082 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. 5082-5082 ◽

Cited By ~ 13

Author(s):

Fred Saad ◽

Daniel Keizman ◽

Joe M. O'Sullivan ◽

Joan Carles ◽

Manfred Wirth ◽

...

Keyword(s):

Overall Survival ◽

Expanded Access ◽

Expanded Access Program ◽

Radium 223 ◽

Access Program

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Therapy intensification in high-risk neuroblastoma patients with poor response to standard induction: experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2019-18-4-19-28 ◽

2019 ◽

Vol 18 (4) ◽

pp. 19-28

Author(s):

T. V. Shamanskaya ◽

D. Y. Kachanov ◽

A. V. Dumacheva ◽

M. V. Teleshova ◽

D. V. Shevtcov ◽

...

Keyword(s):

High Risk ◽

Medical Research ◽

Induction Therapy ◽

Poor Response ◽

Research Center ◽

Long Term Results ◽

Type I ◽

Pediatric Hematology ◽

National Medical

High-risk neuroblastoma (NB) is characterized by unsatisfactory treatment results and low probability of long-term survival despite the multimodal therapeutic approach (chemotherapy, surgical treatment, radiation therapy, autologous hematopoietic stem cell transplantation, etc.). One of the prognostic factors in this cohort of patients is the response to induction therapy. The article presents the experience of the intensification of induction therapy in 12 patients with high-risk NB with a poor response (mixed response, stable disease) to standard induction therapy who received treatment at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, assessing its impact on the prognosis of the disease. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients received an additional two courses of chemotherapy with the inclusion of a type I topoisomerase inhibitor topotecan (TCE – topotecan, cyclophosphamide, etoposide). This regimen of intensification of therapy has demonstrated its feasibility. The main grade 3–4 toxicity was hematologic. An improvement in response was achieved in 5/12 (41.6%) patients. However, long-term results of therapy remained unsatisfactory. The 3-year EFS was 16.7% (95% CI 0.0–37.8), the 3-year OS was 50.0% (95% CI 21.7–78.3). Thus, the intensification of therapy in patients with high-risk NB with a poor response to standard induction therapy did not improve treatment outcomes.

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Modern radiation therapy in part of treatment primary mediastinal (thymic) B-large cell lymphoma (results of 131 patients treated at N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation)

Modern Oncology ◽

10.26442/18151434.2018.4.180142 ◽

2018 ◽

Vol 20 (4) ◽

pp. 5-15

Author(s):

O P Trofimova ◽

I Z Zavodnova ◽

G S Tumyan ◽

Yu I Pryamikova ◽

N V Volkova ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Medical Research ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

Research Center ◽

Lymphoproliferative Diseases ◽

Free Survival ◽

National Medical

Background. For many decades of the twentieth century, radiation therapy has played a leading role in the treatment of patients with lymphoproliferative diseases, which are highly susceptible to ionizing radiation by neoplasms. But due to the effective development of chemotherapy, the discovery and rapid introduction of targeted drugs into practice, the role of radiation treatment in various types of lymphomas becomes less defined in many clinical situations. Primary mediastinal (thymic) B-cell lymphoma (PMBCL) belongs to the primary extranodal tumors and originate from a thymic medullary B cell. The disease has specific morphoimmunological and genetic characteristics that allows it to be identified from the others similar in manifestations lymphoproliferative diseases. The standard of treatment for PMBCL is immunochemotherapy with subsequent irradiation of a residual tumor in the mediastinum. Currently, the benefits of one chemotherapy regimen over the other ones have not been shown in controlled studies. Aim. To study the modern approaches to the chemoradiotherapy in PMBCL patients with an attempt to "individualize" them depending on various prognostic factors. Methods. The study conducted a thorough analysis of the treatment results of 131 patients with PMBCL who were treated in the N.N.Blokhin National Medical Research Center of Oncology from 2005 to 2017. More than half of the patients were women (58%), the median age was 30 years. At different historical periods, the treatment of PMBCL was applied according to different chemotherapy regimens: MACOP-B+R - 55 (42%), R-CHOP - 40 (30.5%), R-DA-EPOCH - 36 (27.5%); 99 patients received radiation therapy. Results. The efficacy of treatment in the whole group of PMBCL patients was high: remission was achieved in 87% of patients, 3-year progression-free survival was 78%, and overall survival was 88%. With a median follow-up of 37 months, 17 (13%) of 131 patients had a relapse or progression of the disease within 13 months from the start of treatment; no late relapses were detected. Treatment of this group was ineffective: the 12-month overall survival did not exceed 37%. In the group of 99 patients with immunochemoradiotherapy, high rates of 3-year overall survival and progression-free survival (with a median of 37 months) were achieved - 91% and 88%, respectively. It has been shown that intensive immunochemotherapy regimens (R-MACOP-B, R-EPOCH) do not differ in efficacy and have statistically significant advantages over the standard R-CHOP regimen. Positron emission tomography (PET) is an important prognostic tool in the treatment of patients with PMBCL: 3-year progression-free survival in the PET-negative group was 92% compared with 26% in the PET-positive group. The frequency of radiation damage to the lungs during conventional and 3D conformal radiation therapy was analyzed. Conclusion. The algorithm of optimal treatment for PMBCL patients was determined based on clinical factors, the drug treatment program, the degree of regression of the tumor and its metabolic activity, volume and method of irradiation.

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