Clarithromycin overcomes resistance to lenalidomide and dexamethasone in multiple myeloma.
The combination of clarithromycin, lenalidomide and dexamethasone (BiRd) has led to highly durable responses in newly diagnosed myeloma. However, the ability of clarithromycin to overcome resistance to lenalidomide and dexamethasone (Rd) is not known. To study this, we performed a retrospective analysis of 24 patients with myeloma for which clarithromycin was added to Rd at the time of progression on Rd. The median number of prior therapies was 3 (range 1-8). The best response was complete response (CR) in one (4.2%), very good partial response (VGPR) in one (4.2%) and partial response in eight (33.3%) patients. Ten patients, 41.7% (95% CI: 22.1, 63.4), achieved ≥PR. The median time to response was 4.4 months (range 1-13.6 months) and the median duration of response was 6.9 months (range 3-52.2 months). The clinical benefit rate (CR + VGPR + PR + MR) was 45.8% (95% CI 25.6, 67.2). The median progression-free survival was 4 months. Median overall survival was 25 months with a median follow-up of 27.5 months. The regimen was well tolerated and only 2 patients needed a clarithromycin dose reduction. Addition of clarithromycin to Rd can overcome resistance to Rd in a subset of patients and lead to durable clinical responses.
Levine Cancer Institute, Carolinas Healthcare System, Charlotte, North Carolina.
Nilanjan
N
Ghosh
Noah
N
Tucker
Marianna
M
Zahurak
Jocelyn
J
Wozney
Ivan
I
Borrello
Carol Ann
CA
Huff
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D017291:Clarithromycin / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide; D017291:Clarithromycin