Clarithromycin (Biaxin®), Low Dose Thalidomide and Dexamethasone (BLT-D) in Newly Diagnosed and Previously Treated African American Patients with Multiple Myeloma: A Retrospective, Single Institution Experience.

Introduction: African-Americans (AA) are twice as likely to develop multiple myeloma (MM) than Caucasians but are largely underrepresented in clinical trials. Thalidmode plus dexamethasone is an established therapy in MM. Biaxin® may augment the efficacy of this combination possibly via potentiating steroid activity (M. Coleman, et al. Leuk Lymphoma 2002, R. Niesvizky, et al. Blood 2003, Abs #832).

Methods: We conducted a retrospective review of all AA patients (pts) with symptomatic MM treated with BLT-D from 2002-present. Treatment consisted of Thalidomide 50–200mg daily, Biaxin 500mg twice daily and dexamethasone 40mg weekly. All pts received monthly bisphosphonate therapy and aspirin 81–325mg daily. Response criteria was defined as follows: complete response (CR) = no detectable M-protein, marrow plasma cells <5%; very good partial response (VGPR) = decrease in M-protein by >90%; partial response (PR) = decrease in M-protein by >50%; stable disease (SD) = M-protein decrease by <50% without clinical progression; no response (NR)= progression with no change or increase in M-protein or response <4wks. Progression free survival (PFS) was defined from the start of BLT-D until discontinuation or change in therapy due to progressive disease as clinically indicated. Toxicity was graded according to WHO criteria.

Results:15 pts received BLT-D and their characteristics were as follows: all were males; median age 66 (range 30–78); IgG=53%, IgA=20%, light chain only=27%; Durie-Salmon stage I=20%, II=33%, III=47%; International Staging System stage I=20%, II=47%, III=13%, undefined = 20%; 7 were previously treated (5 pts had 1 prior regimen, 2 pts had ≥2 prior regimens). In previously treated pts (n=7) responses were as follows: no CR, 2 VGPR (28%), 3 PR (43%), 1 SD (14%) and 1 NR (14%) for an overall response rate (ORR) of 87%. Their duration of treatment ranged from 4–32 mos and median PFS in responders (VGPR+PR+SD) was 29.5 mos (range 23–35). 3 pts had BLT-D discontinued after 12–15 months of therapy and remained in stable plateau phase off therapy for > 1 year; one was referred for ASCT after 14 mo; one continues stable at 15 mo and the third relapsed at 12 months but failed to respond again to BLT-D. Responses in treatment naive pts (n=8) were as follows: no CR, 3 VGPR (38%), 1 PR (13%) and 2 SD (25%), 2 NR (25%) for an ORR of 75%. Their duration of therapy ranged from 3–20 mos and median PFS in responding patients was 11 mos (range 7–20). The longest survivor in this group (37 mos) received an ASCT after 12 mos of therapy. 13 pts (87%) remain alive at a median follow-up of 24 mos (range 8–37). Grade 3–4 toxicity consisted of 3 DVTs + 1 PE (27%), 5 hypergycemias (33%), 2 infections (13%) and 1 peripheral neuropathy (7%). Additionally, 1 pt developed superficial thrombophlebitis; 1 QT prolongation resolving with Biaxin discontinuation; 5 others with neuropathy; and 2 others with hyperglycemia.

Conclusion: BLT-D is feasible and effective therapy in African-American patients with MM and is capable of inducing durable responses. However, we encountered significant thrombotic and endocrine toxicity that appears out of proportion to what has been previously reported with thalidomide plus dexamethasone alone. Furthermore, aspirin thromboprophylaxis at daily doses of 81–325 mg appears suboptimal in preventing thromboembolic events in this group of patients when prescribed this regimen.