Interim Analysis of a Phase II Trial of Bortezomib in Patients with Multiple Myeloma Who Failed To Achieve a Complete Response to Autologous Peripheral Blood Stem Cell Transplantation.

The majority of patients (pts) with multiple myeloma (MM) fail to achieve a complete response (CR) with standard induction therapy (ie, VAD, DVD, Thal-Dex). Bortezomib has been shown to induce a CR in ~10% of subjects with refractory/relapsed MM. This study was conducted to assess the safety and efficacy of bortezomib in converting pts, who failed to achieve a CR to high-dose chemotherapy, to complete responders.

A total of 68 pts are targeted for enrollment on the current study protocol. To date, 20 pts have enrolled and are the subject of this planned safety analysis. As of this submission, 18 pts have been treated and 16 pts have either completed or discontinued treatment. All pts have received at least one dose of bortezomib according to the following schedule. Bortezomib was administered at a dose of 1.3 mg/m² via IV push on Days 1, 4, 8, and 11 every 21-days for 4 cycles. Patients who failed to demonstrate disease progression were eligible for 4 additional cycles of therapy administered according to the above schedule. The demographic data of the first 20 subjects enrolled are summarized in the table below.

Sixteen of 20 pts enrolled have now completed the study. Patients received a median of 4 cycles (range, 3–8). Reasons for discontinuation included: adverse events (n=3 neuropathy (± fatigue) and n=1 fatigue with constipation) and other (n=1 each, progressive disease, carpal tunnel, deemed ineligible). Six patients had dose(s) delayed and/or reduced due to adverse events (peripheral neuropathy; fatigue; neutropenia and herpes zoster; fatigue with neuropathy; nausea, vomiting, diarrhea, and sinus infection; hypertension, and fatigue with constipation).

Treatment-related Grade 3–4 toxicities have been infrequent and include: asthenia, peripheral neuropathy, and thrombocytopenia (11% each) and hypertension, abdominal pain, and neutropenia (5.6% each). Grade 4 toxicity was limited to 2 pts with thrombocytopenia. No life threatening infections or reactivation of herpes zoster have been observed. Bortezomib when administered in the post-transplant setting appears to be safe and well tolerated. Neuropathy and thrombocytopenia appear to be major factors in patient discontinuation. Following review of this planned interim analysis for safety, the study continues to accrue toward completion.