Metastatic cancer immunotherapy

Currently, the overall survival after using im­mu­no­therapeutic agents has reached 24 months. This case is important for understanding the possibilities of administering chemotherapy and immunotherapy successively, although we cannot make assessments regarding survival.

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  • Stage IV Melanoma Cancer Treatment Options Explained: Immunotherapy and Targeted Therapy Imunoterapia în cancer: mecanismele imunologice şi rolul lor în terapie Imunoterapia în cancer: mecanismele imunologice şi rolul lor în terapie Metastatic cancer immunotherapy.

This case demonstrates the pos­si­bi­li­ty of obtaining a complete remission for the com­bi­na­tion ipilimumab IPI plus nivolumab NIVO fol­lowed by chemotherapy. Therefore, this case could sup­port the hypothesis regarding a good combination of im­mu­no­therapeutic agents administered after che­mo­the­ra­py which in­creases the immunogenicity of tumor cells.

Another pe­cu­lia­ri­ty of this case is the onset, after the ad­mi­nis­tra­tion of IPI plus NIVO, of a third-degree toxicity which was com­ple­tely remitted, and after that the patient received without any toxicity the subsequent chemotherapy of eight series of dacarbazine.

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Keywords malignant melanoma, complete remission, immunotherapy Rezumat Melanomul malign metastatic are un prognostic nefavorabil, cu o supravieţuire globală care până nu demult era de luni. Actualmente, prin apariţia agenţilor imunoterapici, supravieţuirea globală a ajuns la 24 de luni. Cazul pe care îl prezentăm, deşi nu putem face aprecieri asupra su­pra­vie­ţuirii, este important pentru înţelegerea posibilităţii de a administra succesiv chimioterapia şi imunoterapia.

Combinaţie de agenţi imunoterapeutici utilizată în melanomul metastatic – prezentare de caz

Acest caz demonstrează posibilitatea obţinerii unei remisiuni com­plete prin combinaţia ipilimumab IPI plus nivolumab NIVO urmată de chimioterapie. De asemenea, acest caz sus­ţine ipoteza unui răspuns bun al combinaţiei de agenţi imunoterapeutici administraţi după chimioterapie care ar creşte imunogenicitatea celulelor tumorale.

O altă par­ti­cu­la­ritate a evoluţiei cazului este apariţia, după prima ad­mi­nis­tra­re de IPI plus NIVO, a unei toxicităţi de gradul al III-lea care s-a re­mis complet şi a permis administrarea ulterioară de opt serii de dacarbazină. Cuvinte cheie melanom malign remisiune completă imunoterapie Introduction Melanoma, an aggressive form of skin cancer, resulted from the transformation of melanocytes into malignant cells, is responsible for most of the deaths related to skin cancer 1.

The incidence rates for melanoma slaboficat slim prospect increasing. Inin Europe, melanoma was the fifth and eighth type of cancer, with more estimated new cases metastatic cancer immunotherapy females and males, respectively. Most of the melanomas are normally located in the skin, but other locations are possible: eyes, ears, gastrointestinal tract, leptomeninges and oral and genital mucous membranes 2.

In Romania, according to the Globocan data, in we had metastatic cancer immunotherapy cases of skin melanoma and deaths were related to this type of cancer. We present a compelling case of a year-old patient, diagnosed with skin melanoma, Clark IV level, in pT3NxMxwith multiple metastases few months later after one month of treatment with alpha 2b interferon, which subsequently obtained complete remission after one pre-immunotherapy series of DTIC, one series of dual immunotherapy and 8 series of post-immunotherapy chemotherapy with DTIC.

Case presentation M. From the personal pathological history, we mention a hypercholesterolemia and a chronic ischemic heart disease diagnosed many years ago. Disease history After surgical removal Julythe histopathology was malign melanoma, Breslow index 3. The following IHC results confirmed the histopathology.

The initial CT scan of the thorax, abdomen and head 1. The sentinel node procedure was performed after lymphoscintigraphy and was positive at metastatic cancer immunotherapy axillary and inguinal level. Figure 1.

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PET-CT on 4. Multiple active nodes On the 27th of August,the patient underwent surgical removal of the lymphatic block from the right armpit diagnosed later on the HP bulletin as malignant metastasis and large postsurgical scar excision from the right abdominal flank which proved to be free of malignant cells on the HP exam.

Metastatic cancer immunotherapy inguinal block was not identified during surgical intervention and was diagnosed as lymphangitis at this level. In Novemberthe patient received the available treatment at that time with Intron® alpha 2b interferon6 doses of 5 millions IU at three days. PET-CT scan from December revealed multiple metabolic active sites bilateral pleural and lung nodules, lymph node block at the right armpit level, liver, bone and adrenal active nodes — Figure 1.

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Head CT did not reveal the existence of metastases. At that moment, the patient received chemotherapy with dacarbazine DTIC. The delay of administration of immunotherapy was due to the fact that in Romania we waited for the approval of immunotherapy with dual blockade, IPI plus NIVO.

We stopped the immunotherapy and administrated corticosteroid medication. The patient recovered his liver function, reaching normal values of liver enzymes. Figure 2. Liver node active Figure 3.

Metastatic cancer immunotherapy. Delivering cancer treatment on a nanodisc helps eliminate tumors

PET-CT on Lung node active In Februarydue to the third-grade toxicity of the liver, we replaced the immunotherapy with chemotherapy with DTIC mg i. Figures 4 and 6 reveal the disappearance of lung and pleural metastases. Unfortunately, we have no images that show the disappearance of the liver and bone metastases, but only an interpretation bulletin. The CT from July revealed the complete remission of pleural and lung metastases Figures metastatic cancer immunotherapy and 6.

The CT scan from 4. Figure 4. CT on Lung node absent Figure 5. Pleural metastasis. Disappearance of pleural metastasis Discussion In the last years, the treatment strategy for advanced melanoma has progressed. New agents are significantly prolonging the survival of patients with advanced metastatic melanoma 3.

Johns Hopkins Medicine Summary: In an expanded, three-year clinical trial of 86 patients with colorectal and 11 other kinds of cancer that have so-called 'mismatch repair' genetic defects, scientists have found that half of the patients respond to an immunotherapy drug called pembrolizumab Keytruda.

These agents are part of targeted therapies — selective inhibitors of the oncogene BRAF and MAPK pathway directly, and immunotherapies — immune checkpoint metastatic cancer immunotherapy targeting cytotoxic T lymphocyte associated antigen-4 CTLA-4 and PD-1, like ipilimumab and nivolumab 4. Before these two types of agents, patients with metastatic disease had a median survival between 8 and 12 months. Due to the use of these therapies, the survival period is now at least 24 months 3. Even when we compare the systemic immunotherapy that we used before with the new immunotherapeutic agents CTLA4 and PDL1 inhibitorswe see a big difference in results.

Thus, the first immunotherapeutic approaches were cytokine therapy, such as interferon alpha IFN-a and interleukin-2 IL Nonetheless, these agents were not associated with durable responses or enough improvements in survival for the most part of the patients.

Metastatic cancer immunotherapy

These therapies metastatic cancer immunotherapy also often associated with severe adverse effects AEs and toxicity 6,7. Somewhat, the same results are reported with chemotherapy as a systemic therapy in advanced melanoma. This therapy is well tolerated, but has low response rates 7. An alkylating agent, dacarbazine 5-[3,3-dimethyltriazenyl]-imidazolecarboxamide, or DTICis one metastatic cancer immunotherapy the agents used for advanced melanoma.

A pooled analysis of 23 randomized, controlled trials showed preț de îndepărtare a negi the objective response rate ORR for 1, patients receiving dacarbazine in monotherapy was The vast majority of these responses were partial This study was amended to include the dose and schedule for nivolumab plus ipilimumab that was later evaluated in phase II CheckMate and phase III CheckMate randomized studies.

CheckMate also demonstrated significantly improved progression-free survival PFS and ORR for nivolumab plus ipilimumab, as well as nivolumab alone versus ipilimumab alone in patients with previously untreated advanced melanoma At a minimum follow-up of 18 months, the median progression-free survival was 8.

The objective response rate was The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most of them resolving metastatic cancer immunotherapy appropriate management Conclusions This case argues for a complete remission, in the case of metastatic malignant melanoma, after a single administration of a combination of ipilimumab plus nivolumab.

Prior administration of a dacarba­zine dose could have a facilitating effect on the response to this combination of immunotherapeutic agents: cytotoxic T lymphocyte-associated antigen 4 inhibitor ipilimumab plus PD-1 inhibitor nivolumab. Chemotherapy could make a re activation of tumor-targeting immune responses and can promote such responses to immunotherapeutic agents by increasing the immunogenicity of malignant cells.

Another aspect highlighted by this case is the acute third-degree toxicity common toxicity criteria which has completely recovered metastatic cancer immunotherapy stopping the immunotherapy and at the administration of a liver protector.

But another problem is also whether the criteria for assessing cytostatic toxicity are applicable in case of immunotherapy. The patient will be monitored for the duration of remission and survival, a challenge being the treatment indicated in a possible resumption of the disease evolution. Conflicts of interests: The authors declare no conflict of interests. J Am Acad Dermatol.

Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in Eur J Cancer. Survival of patients with advanced metastatic melanoma: the impact of novel therapies — update Rubin K. MAPK pathway-targeted therapies: care and management of uniquetoxicities in patients with advanced melanoma. Clin J Oncol Nurs.

J Immunother Cancer. Immunotherapy of melanoma. Wspolczesna Onkol.

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Treatment of metastatic melanoma: an overview. Oncology Williston Metastatic cancer immunotherapy. Treatments for metastatic melanoma: Synthesis of evidence from randomized trials. Cancer Treat Rev. Dimethyl triazeno imidazole carboxamide and combination therapy for melanoma IV.

Late results after complete response to chemotherapy Central Oncology Group protocols, and A. Nivolumab plus ipilimumab in advanced melanoma.

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N Engl J Med. Improved survival with ipilimumab in patients with metastatic melanoma. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.

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Lancet Oncol. Combined nivolumab and metastatic cancer immunotherapy or monotherapy in untreated melanoma.

Overall survival with combined nivolumab and ipilimumab in advanced melanoma. J Clin Oncol. JAMA Oncol. Articole din ediţiile anterioare.