Efficacy and Safety of Clarithromycin, Lenalidomide and Dexamethasone (Bird) Therapy for Japanese Patients with Relapsed or Refractory Multiple Myeloma

*Corresponding author: Hitoshi Hanamoto*, Aki Fujii, Mariko Fujita, Ko Fujimoto, Ryosuke Fujiwara and Kazuo Tsubaki

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original research



It is difficult for the elderly, those with complications, and those who live in remote areas to visit the hospital, and as a result, there are limits on the drugs they are able to use. It is therefore effective to prescribe such patients oral medications that have few adverse effects and in regimens that require few hospital visits. Clarithromycin can induce cell death by autophagy and it has a direct antitumor effect. There have been reports of the outcomes of Lenalidomide and Dexamethasone therapy with Clarithromycin which is administered orally and is safe on multiple myeloma. However, in Japan, there have been few studies. Here, we report on Clarithromycin, Lenalidomide and Dexamethasone therapy in our hospital.


We analyzed 7 patients with relapsed refractory or refractory multiple myeloma who were treated at this hospital between January 2012 and December 2014. The Clarithromycin, Lenalidomide and Dexamethasone therapy were administered in a 28-day cycle as follows: Clarithromycin 400 mg/day for 28-days, Lenalidomide 15 mg/day for 21-days, and Dexamethasone was administered in a dose of 20 mg once per week. The response criteria used were standard International Myeloma Working Group (IMWG) Uniform Response Criteria. and adverse events were graded according to the national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) Ver. 4. Statistical analysis was performed using Easy R (EZR).


The response to Clarithromycin, Lenalidomide and Dexamethasone therapy were selective catalytic reduction (sCR) in 2 patients, CR in 1 patient, per rectum (PR) in 3 patients, and standard deviation (SD) in 1 patient. Response rates of PR or better were observed in 86% of the patients. Duration of response was median 316-days (range, 160-522-days). Median oculus sinister (OS) period was 1,907 days. Median OS following discontinuation of the study was 1,385 days. Hematological adverse events were G1-2 anemia in 3 patients and G3-4 anemia in 1 patient. G1-2 thrombocytopenia was observed in 1 patient and G3-4 thrombocytopenia was observed in 1 patient. Leukopenia of G1-2 was observed in 6 patients but G3 was not observed. Non-hematological adverse events were G1-2 liver disorder in 6 patients, G1-2 skin rash in 3 patients, and G1-2 constipation in 2 patients. G4 adverse events were fainting and duodenal ulcer in 1 patient each.


Clarithromycin, Lenalidomide and Dexamethasone can be safely and effectively administered in the relapsed refractory multiple myeloma


Multiple myeloma; Bird; Clarithromycin, lethal dose (Ld).