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HIV-linked multiple myeloma responds to thalidomide. (No Immunosuppression Seen).

BETHESDA, MD. -- Thalidomide may be particularly useful for treating HIV-associated multiple myeloma, Dr. David M. Aboulafia reported at an international conference on malignancies in AIDS and other immunodeficiencies.

"Early results in several phase II clinical trials have demonstrated the activity and safety of thalidomide in advanced or refractory multiple myeloma [in HIV-negative patients], with response rates ranging from 32% to 66%," said Dr. Aboulafia of the division of hematology/oncology at Virginia Mason Medical Center, Seattle.

Thalidomide is "an interesting and appealing therapy for HIV-infected patients" because it doesn't induce immunosuppression and doesn't appear to interfere with the pharmacokinetics of highly active antiretroviral therapy, he noted at the conference, which was sponsored by the National Cancer Institute.

Thalidomide also doesn't cause stomatitis, hair loss, or nausea and vomiting. Further, the drug improves wasting syndrome and aphthous ulcers. It also is believed to exert effects against Kaposi's sarcoma.

Dr. Aboulafia reported the case of a 46-year-old HIV-positive man who developed increasing fatigue and dyspnea on exertion. He was found to have anemia secondary to multiple myeloma. He had no Kaposi's lesions but was seropositive for human herpesvirus 8.

The patient began a regimen of oral thalidomide (400 mg daily), clarithromycin (250 mg twice daily), and dexamethasone (40 mg daily), for 4 days each month. That regimen has been reported to produce responses in all 24 patients treated in a single study of multiple myeloma unrelated to HIM.

In that study, bone marrow plasma cells decreased, hemoglobin level increased, and bone pain declined. However, the role of clarithromycin and dexamethasone in this regimen remains to be clarified, Dr. Aboulafia noted.

In his patient, the anemia resolved and energy level improved within 3 months of starting thalidomide. A bone-marrow biopsy at 6 months showed resolution of plasmacytosis, and immunoperoxidase staining failed to reveal any monoclonal plasma cell populations.

The patient reported no significant toxicities with this drug regimen.

After 12 months, the patient reported feeling energetic, and his hematocrit remained within normal limits. His CD4+ count remained stable at 680 cells/[micro]L and his HIV viral load remained stable at less than 50 copies/mL. The thalidomide dose was reduced to 250 mg/day because of mild peripheral neuropathy.

The patient continues to do well more than a year after his multiple myeloma diagnosis. He "has achieved a dramatic antitumor response without [an adverse impact] on his immune state or performance status," Dr. Aboulafia said.

"As treatment of HIV infection improves, resulting in prolonged survival of immunodeficient individuals, it is possible that an expanding array of associated malignancies, including multiple myeloma, will be identified," he added.

Thalidomide and other novel modulators of tumor necrosis factor, inter-leukin-6, and angiogenesis should be examined for these patients, he said.
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Author:Moon, Mary Ann
Publication:Internal Medicine News
Date:Oct 15, 2002
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