BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

Abstract

This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine Mprotein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in Mprotein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as

The role of complete response in multiple myeloma

“…[45][46][47]72 With prolonged treatment with the combination of lenalidomide plus dexamethasone, CR was achieved in 39% of cases, and 74% of patients had at least a 90% decrease of the M-component. 73 The same is true in the context of ASCT plus novel agents. Induction treatments with thalidomide or bortezomib plus dexamethasone yield 6% to 19% CR and 19% to 46% CR/VGPR before ASCT.…”

Pathogenesis and treatment of renal failure in multiple myeloma

“…76 However, in this report, only five patients had a serum creatinine 42 mg per 100 ml. Another study investigating the combination of lenalidomide with clarithromycin and dexamethasone showed that patients with a baseline creatinine clearance o40 ml/min were 8.4 times more likely to require lenalidomide dose reduction due to grade 3 or grade 4 myelosuppression, 77,78 thus indicating the need for lenalidomide dose adjustments according to renal function. Recommendations for lenalidomide use in patients with renal impairment have been formulated on the basis of a pharmacokinetic study in 30 patients with various degrees of renal impairment.…”

Six‐month oral clarithromycin regimen is safe and active in extranodal marginal zone B‐cell lymphomas: final results of a single‐centre phase II trial

“…These preclinical data constitute the rationale for prospective clinical trials addressing the antineoplastic activity of macrolides. In particular, the combination of clarithromycin with other immunomodulatory agents has been associated with encouraging results in prospective trials on multiple myeloma and Waldenström macroglobulinemia (Niesvizky et al, 2008). Additionally, anecdotal case reports suggest an antineoplastic effect of clarithromycin in patients with marginal zone B-cell lymphoma (MZL) of the gastrointestinal tract (Arima & Tsudo, 2003;Matsumoto & Iida, 2005 infection (histology, breath test, serology, and/or cytotoxin associated gene A in faeces).…”