Patient markers pinpoint response to bortezomib Rx

Australian researchers reported that multiple myeloma patients who expressed cyclin DI were more likely to achieve a response to treatment with bortezomib (Velcade). Mark A. Dawson, MD, Andrew Spenser, MD, and colleagues aimed to identify the patients who would fare best with bortezomib salvage therapy. Th eir group analyzed the baseline clinical variables, and profi led the baseline expression of a broad range of immunohistochemical markers of cell cycle activity, apoptosis, and angiogenesis, in a large cohort of multiple relapsed myeloma patients. The subjects had been recruited to prospective multicenter trials that assessed the effi cacy of bortezomib salvage therapy.

According to their results, complete or partial response to bortezomib salvage therapy was associated with a previous history of complete response to alternative antimyeloma treatment. Patients who achieved a response to bortezomib and those patients who expressed cyclin D1 at baseline showed a significant survival advantage. Patients who expressed FGFR3, a marker for poor prognosis, responded equally well and had similar outcomes with bortezomib, compared with FGFR3-negative patients.

On the other hand, patients who expressed p16INK4A, cytoplasmic p53, and the highest intensity of Bcl-2 staining had a poor response, they stated (Clinical Cancer Research 15:714-722, 2009).

“Bortezomib has off ered some patients with relapsed and refractory disease an opportunity for prolonged survival,” the authors wrote. “However, there remains a paucity of data in patients treated with bortezomib that accurately delineates and identifi es such patients. This information is crucial to guide management.” Baseline clinical variables, and selective immunohistochemical markers expressed by patients, may be used eff ectively to identify patients who are most likely to achieve a meaningful clinical response to bortezomib salvage therapy, they said.

The investigators are from several Australian institutions, including Alfred Hospital, Royal Melbourne Hospital, and Royal Adelaide Hospital Cancer Centre.