Strong Responses Seen With Bortezomib-based Therapy After Relapse in Multiple Myeloma

TON - April 2010 Vol 3, No 2 — June 2, 2010

For patients with relapsed or refractory multiple myeloma (MM), bortezomib-based therapy is effective after lenalidomide plus dexamethasone (LD), according to a Canadian study that evaluated sequencing of novel agents presented at the 51st Annual Meeting and Exposition of the American Society of Hematology.

"The optimal sequencing of novel agents in MM is not certain. Due to limitations in provincial drug funding in Ontario, Canada, we had a unique opportunity to evaluate the efficacy of bortezomib in patients who progressed after treatment with lenalidomide plus dexamethasone, provided through ex - panded access programs and clinical trials for relapsed or refractory disease," said principal investigator Donna Reece, MD, associate professor and director of the program for multiple myeloma and related diseases at Princess Margaret Hospital, Toronto.

Outcomes were analyzed for 49 patients who received LD for recurrent MM (first- to fourth-line), followed by bortezomib-based regimens for their next relapse, without any interim therapy. Thirty-nine (80%) had also undergone autologous stemcell transplantation. Patients received bortezomib alone (33%), bortezomib plus steroids (47%), bortezomib plus prednisone and cyclophosphamide (8%), bortezomib plus thalidomide and dexamethasone (4%), or bor tezomib plus another agent (8%).

The median treatment duration of LD was 5.3 months. For that regimen, the best clinical response included near-complete response (nCR) in 6%, very good partial response (VGPR) in 6%, partial response (PR) in 51%, minimal response (MR) in 12%, stable disease (SD) in 19%, and progressive disease (PD) in 25%.

After relapse, when patients began a bortezomib-based treatment, median follow-up was 6.5 months and the best responses to those regimens included complete response or nCR in 2%, VGPR in 16%, PR in 26%, MR in 14%, SD in 16%, and PD in 24%.

Median progression-free survival (PFS) was 4.0 months, with a 12% median 1-year PFS rate. Median overall survival (OS) was 9.5 months, with a 31% median 1-year survival rate, Reece reported.

Investigators assessed a number of factors for their prognostic effects on PFS and OS, including age at diagnosis, gender, subtype, duration of initial therapy, and response to LD, but only the patient's response to the bortezomib-based therapy was significant (P <.0001 for PFS and P = .002 for OS).

"The PFS and OS observed after bortezomib-based therapy is not de pendent on the response to lenalidomide plus dexamethasone," Reece said.

Patients who achieved at least a PR to bortezomib had a median PFS of 7.3 months, compared with 2.0 months for patients with MR or less. One-year PFS was 29% versus 13%, respectively. Similarly, for OS, a response of PR or better was associated with a median OS of 14.3 months, versus 3.9 months for a lesser response, and 1-year OS was observed in 12% and 14%, respectively.

"We concluded that treatment of sequential multiple myeloma relapses with bortezomib-based therapy after progression on LD produces partial responses or better in 44% of patients, results in a median PFS similar to the 6.2 months seen with bortezomib in less heavily pretreated patients in the APEX trial [Richardson PG, et al.N Engl J Med. 2005;352(24): 2487- 2498], and demonstrates the effectiveness of bortezomib even after exposure to the potent LD combination," Reece said.

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