Bortezomib Targets Long-Lived Plasma Cells, Shows Promise for Lupus

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.