Bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL): Preliminary results of the PINNACLE study

6563 Background: Bortezomib (VELCADE, Vc, Millennium Pharmaceuticals) is a novel proteasome inhibitor effective in relapsed multiple myeloma (MM) and is now being explored in MCL. Methods: Patients (pts) with relapsed or refractory MCL with a maximum of 2 prior therapies received Vc 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of a 21-day cycle for 4 cycles beyond complete response (CR) or up to 1 year unless there was disease progression or toxicity. 102 patients have been enrolled (June 2003 through Nov 2004) in this 3-stage, phase 2 study at 29 sites (28 US, 1 UK). Response was assessed by the investigators using International Workshop criteria, while final results will be based on central radiology review. Results: 48 pts were evaluable for response at the second stage. Baseline characteristics included median age 66 y, 85% male, 88% International Prognostic Index ≥ 2, 40% lactic dehydrogenase > normal, 92% Karnofsky performance score ≥ 70%, 77% ≥ 1 extranodal site, and 57% with 2 prior lines of therapy. Median time from diagnosis was 2.3 y (range 0.2–9.0). A median of 4 cycles was administered. Median follow-up was 6.2 mo. Response rate (CR + unconfirmed CR [Cru] + partial response) was 40% (19/48) with CR + CRu 6% (3/48). Evaluation of time to progression, response duration, and survival is ongoing. Vc was well tolerated. 34% of 102 pt experienced a serious adverse event (SAE); however, only 21 of 46 events were considered related to Vc by the investigator. The most common Vc related SAEs included vomiting, abdominal pain, dehydration, and asthenia. Mean platelet (plt) counts followed a cyclical pattern, decreasing during treatment and recovering to baseline by the next cycle, as seen in MM. Only 9.3% of patients had a nadir plt count < 25,000 cells/μL. Conclusions: These data confirm the activity of Vc in MCL, and an update on the 152 pts scheduled for enrollment in this trial will be presented at the meeting. These results support the rapid development of Vc as a new treatment option for MCL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Celgene, Cell Therapeutics, Millennium Millennium Millennium