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Clarithromycin, Low-Dose Thalidomide, and Dexamethasone Produces Consistent Responses in Myeloma and Waldenstrom’s Macroglobulinemia

Clarithromycin, Low-Dose Thalidomide, and Dexamethasone Produces Consistent Responses in Myeloma and Waldenstrom’s Macroglobulinemia

Seventeen patients with myeloma (13) or Waldenstrom’s macroglobulinemia (4) have been treated at our center with a nonmyelosuppressive combination of oral clarithromycin (Biaxin) at 500 mg twice daily, low-dose oral thalidomide (Thalomid) at 50 mg at bedtime, and oral dexamethasone at 40 mg every week. Treatment also included oral pyridoxine at 100 mg twice daily and oral omeprazole (Prilosec) at 20 mg twice daily for 2 days with dexamethasone.

Dose modifications were as follows: oral clarithromycin reduced to 250 mg twice daily for gastrointestinal symptoms; thalidomide escalated as tolerated by 50 mg biweekly to a maximum of 200 mg/d; and dexamethasone decreased (for endocrine intolerance) to 40 mg every 10 days, every 2 weeks or 20 mg every 2 weeks as maximally tolerated. Therapy is ongoing, with a duration of 3 to 24 weeks, and a median/mean of 12 weeks. Of 17 patients, 1 is post–stem-cell transplant, 3 received “high-dose” nontransplant chemotherapy, 9 received conventional chemotherapy, and 4 were previously untreated.

Three patients have not completed a minimum of 6 weeks of treatment, and thus are not assessable. Of 14 evaluable patients, all responded: 3 complete responses with no evidence of disease, 5 complete responses with normal immunoglobulin levels but a persistent monoclonal spike, and 6 partial responses with a greater than 75% reduction of the monoclonal spike. Responses were mirrored by similar improvement in bone marrow status. Improvement in blood counts and/or normal immunoglobulins was observed in most patients. Responses occurred by 6 weeks, and are ongoing and proportionate to medication doses (improvement with increased drug dose, less improvement with lower doses). Resistance has not been encountered; responses were unrelated to prior chemosensitivity or resistance.

Three patients required a reduced clarithromycin dose due to gastrointestinal intolerance or Clostridium difficile, all patients required a reduction in thalidomide dosing (median tolerated dose: 100 mg/d), and 14 patients required reduction in dexamethasone dosing. All patients sustained grade 1–3+ reversible neurotoxicity, including peripheral and/or autonomic neuropathy and drowsiness requiring dose reduction. Withdrawal of treatment resulted in rapid return of disease, suggesting that response may be cytokine mediated.

CONCLUSION: A regimen of clarithromycin, low-dose thalidomide, and dexamethasone administered daily is a highly effective regimen in virtually all myeloma and Waldenstrom’s macroglobulinemia patients evaluated to date. Results are dependent on a balance of treatment intensity with quality of life.

Click here to read James R. Berenson's commentary on this abstract.

 
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