Bortezomib is the first proteasome inhibitor with activity in humans with multiple myeloma and evidence of activity as a single agent in relapsed, refractory non-Hodgkin's disease.

André Goy, MD, head of lymphoma, Hackensack University Medical Center, Hackensack, New Jersey, United States, presented the second stage interim analysis of the PINNACLE phase 2 study here on June 3^rd.

The multicentre study started on January 2003 in the United States and Europe and involves 152 patients with relapsed or refractory MCL and a maximum of 2 prior therapies.

Bortezomib was given at 1.3 mg/m² by intravenous bolus on days 1, 4, 8, and 11 of a 21-day cycle for 4 cycles beyond complete response or up to 1 year, unless stopped because of progression or toxicity. Patients received bortezomib for a median of 4.5 cycles.

Results showed an overall response rate of 42% with a complete and unconfirmed complete response rate of 8%. Median duration of response was 6.2 months and median time to progression was 4.3 months.

Adverse events were similar to those observed in other clinical trials, Dr. Goy said. Vomiting, abdominal pain, dehydration, and asthaenia were the most common bortezomib-related serious adverse events. Toxicities were found to be predictable and manageable and included fatigue, peripheral neuropathy, and gastrointestinal events, he said.

As is generally seen in the treatment of multiple myeloma, Dr. Goy said, thrombocytopenia was cyclical, decreasing during treatment and recovering to baseline by the start of the next cycle.

The US Food and Drug Administration granted bortezomib fast-track status for MCL in November 2004.

Dr. Goy noted that, while results to date are promising and encouraging, there is "still a lot to learn," about bortezomib and MCL. Dosage remains to be established and its use in combination with other agents has not yet been studied, he said.

The research was supported by Millennium Pharmaceuticals in the US and Johnson & Johnson in the UK.


[Presentation title: Treatment With the Protease Inhibitor Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma: Preliminary Results of the PINNACLE Study. Abstract 0268]

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