ASCO: Clarithromycin, lenalidomide and dexamethasone as primary treatment of myeloma

Abstract No: 7545

Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 7545

Authors: R. Niesvizky, D. S. Jayabalan, J. R. Furst, H. J. Cho, R. N. Pearse, F. Zafar, R. W. Lent, J. Tepler, M. W. Schuster, J. P. Leonard, M. Coleman

Abstract:

Background: Lenalidomide (Revlamid [R]) is the leading clinical compound in a new group of drugs called IMiDs. Our group demonstrated that clarithromycin (Biaxin [Bi]) augments tumor mass reduction and improves responses in patients (pts) receiving low-dose thalidomide and/or dexamethasone (D). We report the results of the combination of Bi plus R plus D (BiRD) in newly diagnosed MM.

Methods: A phase II trial designed to accrue 50 pts. A 2-stage design rejects a CR rate of <>30%). Between Nov. 2004 and Jan. 2006, 46 pts have been accrued of which 40 pts are eligible for evaluation. R is given po at 25 mg daily on days 1-21 of a 28-day cycle. D is given po at 40 mg once weekly. Bi is given po at 500 mg bid. Pts receive low dose aspirin (ASA)(81mg) qd as thrombosis (TE) prophylaxis. Responses are defined according to modified EBMTR criteria. Analysis is by intent-to-treat. Patient Selection: Median age: 62.5 years (36-80), Male/Female 25/15, Hgb: 10.6 g/dL (7.2-15.1), Plt 234 k/uL (51-526), β2m: 3 mg/L (0.8-12.8), CRP: 0.6 mg/dL (0.12-14.2), creat: 1.1 mg/dL (0.6-3.1), albumin 3.5 g/dL (2.3-4.9). SD stage IIIa: 48%, stage IIIb: 10% and IIa: 42%. ISS stage I: 50%, stage II: 25% and stage III: 25%. Cytogenetics and FISH: trisomy 11 (10 pts), tetrasomy 11 (3 pts), del13q14 (14 pts), t (4,14) (1pt), t (11,14) (3 pts).

Results: Of the 40 evaluable pts, 38 (95%) have achieved an objective response (>PR) within 3-4 months of Rx with the remaining pts continuing to respond. Seventeen pts (43%) had a >90% reduction of the initial paraprotein. Nearly one third of pts have achieved either a CR (10/40) or a nCR (2/40-continuing on Rx). CR has been confirmed in all pts by normalization of free light chain levels and ratio. The remaining 26 pts (65%) achieved a PR. Of those pts who achieved a PR, 5/26 pts (19%) had >90% reduction in the initial paraprotein. Nineteen pts have experienced grade >3 adverse events. Heme toxicities: anemia (11%), neutropenia (9%) and thrombocytopenia (9%). Non-heme toxicities (NHT) include TE in 7 patients (15%) 2 of them fatal. Four of the TE events were while off ASA. Other NHT include myopathy (6%), GI (4%), and mood (4%).

Conclusions: BiRD therapy is a safe and highly effective primary therapy for symptomatic, treatment-naïve MM.