Thanks, Margie. By way of comparison here is the original study from last year:
Abstract #1306 - 8:45, Monday, December 7, 1998 - Room B214-218TREATMENT OF MULTIPLE MYELOMA
MARKED ANTI-TUMOR EFFECT FROM ANTI-ANGIOGENESIS (AA) THERAPY WITH THALIDOMIDE (T) IN HIGH RISK REFRACTORY MULTIPLE MYELOMA (MM)
S. Singhal, J. Mehta, P. Eddlemon*, P. Gray*, J. Cromer*, R. Desikan*, D. Ayers*, D. Siegel, N. Munshi, E. Anaissie, H. Kantarjian, J. Zeldis*, B. Barlogie
Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas; University of Texas MD Anderson Cancer Center, Houston, Texas; Celgene Corporation, Warren, New Jersey, USA
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MM bone marrow has increased microvessel density. T has AA potential and was evaluated in 89 pts in a dose escalating schedule of 200 mg qd × 14, with increase by 200 mg according to tolerance q 14 d to T max of 800 mg; T was continued at the max tolerated dose until progression/relapse. The median age was 58 yrs (range, 38 to 77); MM was high risk with 78% >24 mos of prior Rx, 84% had one and 63% >2 transplants; 66% had unfavorable cytogenetics (-13, 13q-); and all had disease progression prior to T. The median time on T was 52 d (2231+), and 80% had >28 d of T. With at least monthly M protein analysis of serum and urine and a minimum time of 28 d on T since study initiation, 10 pts (11%) had >75% decline (including BM normalization in 5); 8 (9%) had >50% (<75%) reduction (BM normalized in 4/6); 12 (14%) had >20% (<50%) tumor regression (BM response in 2/8) for a total of 34% paraprotein response associated with resolution of BM plasmacytosis in 11/24 evaluable pts. Responses occurred with similar frequencies in high and low risk cytogenetic groups. The median degree of cytoreduction among the 30 responders was 61% (range, 22 to 99.9). Median times to and duration of response in the 20% group were 29 d (797) and 35 d (2+127+), resp., in the >50% 44 d (1779) and 22+ d (2+99+), in the 75% group 66 d (16109) and 20+ d (2+184+). As of 8/1/98, 39 remain on study including 8/12 with >20%, 7/8 with >50% and 9/10 with >75% response. T was stopped in 50; due to MM progression in 42 (with ensuing death in 14) and because of toxicity in 8 (1 death). Major toxicities (tox) were neurologic (somnolence, dizziness, confusion, tremors, incoordination, tingling, numbness) in 75%, GI (constipation, nausea, vomiting, stomatitis) in 66%, constitutional Sx (weakness, weight loss, fever) in 60%; all of these were generally of moderate degree but prompted T discontinuation due to GI tox in 5, neuro tox in 4, and constitutional Sx tox in 3 - for a total of 8. In conclusion, T has remarkable anti-tumor activity in advanced and high risk MM, justifying its incorporation into combination chemotherapy trials (D.T. PACE-Dex, T, cisplatin, ± Adria, CTX, VP16) which has induced 3 true CR's after 1 cycle among 5 currently evaluable pts (plasma cell leukemia with WBC >120 k, 1 pt; 2 post-transplant fulminant relapses).
Peter
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