Clinical:Ipilimumab Review

MDX 010

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Ipilimumab has not been reviewed or approved by the regulatory authorities ( FDA or EMA). The present article discusses unlabeled/unapproved uses of drugs or products.

Ipilimumab (MDX 010) is a fully human monoclonal antibody discovered and developed by Medarex (now part of Bristol Myers Squibb). Medarex developed genetic mouse carrying human genes produce fully human monoclonal antibodies (Ultimab)

Uses

The drug is in clinical trials for first and second line therapy in melanoma, advanced metastatic melanoma, lung cancer and prostate cancer. The drug has shown dramatic responses in patients with refractory advanced metastatic melanoma in Phase III trials. The results of the Phase III trials released at ASCO 2010 on 5 th June 2010 showed that Ipilimumab increased overall survival by 10 months as compared to 6.4 months in the control group. Dramatic complete responses were observed in patients with advanced melanoma and prostate cancer. These results have created a media blitz around the drug and extensive coverage.

How Ipilimumab Is Taken

A variety of doses and dose regimen have been used in clinical trials. Frequently the drug has been used as 3 mg/kg or 10mg/kg body weight by a 90 minutes iv infusion.

During the induction phase, the dose is given every 3 weeks for 4 cycles.

During the maintenance phase, the dose has been given in the range of once every month to once every 3 months.

How Ipilimumab Works

The monoclonal antibody targets cytotoxic T -Lymphocytes Associated Antigen 4 ( CTLA4). CTLA4 presence on the T cells acts like a switch off the immune system. By neutralizing the CTLA4, ipilimumab activates or stimulates the immune system to clear cancer cells. Cancer patients like humans have different immune system and variable response to an antigen, making it difficult to preselect responders to the mAb treatment and exclude non-responders. Use and validation of biomarkers like total lymphocyte counts, low CRP levels and depigmentation of hair seem to correlate with clinical response, may help preselect patients likely to benefit from treatment.

Image:Human Melanoma SEM Source: http://visualsonline.cancer.gov/retrieve.cfm?imageid=1760&dpi=300&fileformat=jpg

How the body affects Ipilimumab

Since we all have different immune systems, a wide spectrum of responses were observed in cancer patients studied in clinical trials. With cytotoxic drugs a clinical response is expected right after the first dose. In the case of Ipilimumab, it takes time for the immune system to get activated and start clearing tumors. In many patients it took 4-8 months after dosing cycles to observe meaningful clinical response.

Benefits

Melanoma

Ipilimumab is the only drug after decades of failures to increase overall survival in metastatic melanoma patients.

NSCLC

Prostate

Images to be added

Video ASCO 2010.

Side Effects

Activation of the immune system after Ipilimumab results in a unique pattern of immune related adverse drug reactions.

ADR Tables to be added

Risks and Precautions

Interactions

History

Ipilimumab was discovered and developed by Medarex which was acquired by Bristol Myers Squibb in 2008. Medarex developed a mouse model with human genes capable of yielding fully human monoclonal antibodies (mAbs). This was a significant advance in producing fully human mAbs as the conversion of mouse mAbs to human or humanized mAbs requires many steps, is difficult and is costly. Human mAbs produced by Medarex UltiMab technology were 1000 fold more specific binding to target than rodent mAbs.

Controversy

Alternatives

Statistics

Research

Recent discoveries

Current research

Clinical Trials

Interesting Facts

Other Resources

Skin Cancer Malignant Melanoma of Soft Parts Prostate Cancer Prostate Cancer (Clinical) Prostate Cancer Diagnosis and Treatment Prostate Cancer Research Results Prostate Cancer Treatment Lung Cancer Lung Cancer Screening

References

External Links

Republished with modifications from (by self permission of the author)

Ipilimumab (BMS) Review: A Cancer Breakthrough? http://knol.google.com/k/krishan-maggon/ipilimumab-bms-review-a-cancer/3fy5eowy8suq3/107#

French Le Ipilimumab (BMS): un remède magique contre le mélanome ? http://knol.google.com/k/krishan-maggon/le-ipilimumab-bms-un-rem%C3%A8de-magique/3fy5eowy8suq3/116#

Spanish Ipilimumab (BMS) a examen: ¿a por el cáncer? http://knol.google.com/k/krishan-maggon/ipilimumab-bms-a-examen-a-por-el-c%C3%A1ncer/3fy5eowy8suq3/114#[[Category:|Category:]]