Results of Bortezomib (BTZ) Therapy for Myeloma (MM) Patients Relapsing after an Allogeneic Transplant. Preliminary Results Show Efficacy without Induction of GVHD.

Background: The proteosome inhibitor bortezomib (BTZ) has demonstrated significant activity against multiple myeloma (MM). In vitro data suggests that protesome inhibition has immune-modulatory activity that may be relevant in the setting of allogeneic progenitor cell transplantation (allo SCT). However, there is limited experience with the use of BTZ in patients with MM relapsing after an allo SCT.

Purpose: Determine safety, efficacy and effects on GVHD of BTZ in MM patients relapsing after an allo SCT.

Methods: Retrospective analysis of outcomes on 9 MM patients who received BTZ therapy for MM relapse after allo SCT

Results: Nine patients were identified. Median age was 51 (range, 38–64); all patients underwent an allo SCT because of failure to respond or relapse after primary therapy including autograft in 8 patients. At the time of allo SCT; 3 patients had refractory disease and 6 had chemo-sensitive relapses. The median time from allo SCT to relapse was 8.5 months (range, 5–117); the median time from relapse to initiation of BTZ therapy was 3.4 months (range, 0.1–20). BTZ was the 1st line of therapy for relapse in 5 patients. No patient had active GVHD at the time of BTZ therapy. BTZ was given at a dose of 1.3 mg/m2 on days 1,4,8 and 11 every 21–28 days for a median of 3 cycles (range, 2–8). 4 patients received BTZ alone, 3 in combination with DEXA, and 2 in combination with DEXA/THAL. 6 of 9 patients had either a 50% reduction or greater of monoclonal peak, of which 2 were very good PR (>90% reduction) to BTZ. BTZ was well tolerated and no flares of GVHD were seen. Only 2 patients developed severe thrombocytopenia and fatigue, which required discontinuation of therapy (one in the context of relapsing disease). 2 of the responding patients have relapsed at 4 and 7 months after initiation of BTZ therapy. 4 of the 6 responses are ongoing 3 to 9 months after initiation of BTZ therapy. Individual patient outcomes are summarized in Table 1.

Conclusions: BTZ therapy is effective as treatment of MM relapse post allo SCT, it is well tolerated and does not promote GVHD reactions. The response rates would seem to be higher than the responses reported to donor lymphocyte infusions in this setting. BTZ therapy should be studied as front-line therapy for patients relapsing after allo SCT and as maintenance therapy post high risk allograft.

Individual Patient Outcomes