Phase II Trial of Single Agent Bortezomib (VELCADE®) in Patients with Previously Untreated Multiple Myeloma (MM).

摘要: Introduction: Bortezomib, a first in class proteasome inhibitor, has become standard of care the treatment relapsed and refractory MM. A recent randomized Phase 3 trial showed an improvement time to progression (TTP) overall survival relative dexamethasone (dex) patients with MM 1–3 prior lines therapy. In MM, rate -emergent significant peripheral neuropathy (PN) bortezomib was higher baseline neuropathy. The incidence severity PN front-line will be important define. This multi-center, 2 study planned evaluate activity toxicity (in particular PN) single agent previously untreated pts. Methods: Response rate, TTP, tolerability, PN, effect dose modification, symptomatic nutritional supplements on were evaluated untreated, pts. Pts received 1.3 mg/m2 D 1, 4, 8, 11 21-d cycle response assessed every cycles. Dex not permitted. Neurologic evaluation required before after treatment, if developed during therapy. Results: 28 pts have been treated median age 60 yrs, IgG isotype 68% Stage III disease 52%. Analysis best paraprotein ≥ cycles revealed CR 1 (5%) pt PR 8 (36%), for ORR 41% 22 evaluable An additional 5 (23%) achieved MR, stable 6 (27%); progressed (9%). most commonly reported adverse events included fatigue, GI symptoms rash. Neurological performed all pts, including nerve conduction studies (NCS), assessment autonomic function skin biopsy EM imaging small fibers subset (n=19). Six (21%) so far being G2: experienced G3 drug discontinued. Dose modification 4 used PN. Preliminary results neurological testing NCS indicated subclinical at therapy 6/19 (30%) by NCS, fiber, axonal documented treatment-emergent Bortezomib-related otherwise manageable. Conclusion: Single is promising approach newly diagnosed without complications high-dose dex. currently 30%; G2 or greater occurred 21% only (4%) date. Further analysis biopsies ongoing.