Velcade Retreatment Safe, Effective for Relapsed Myeloma

March 1, 2007

Repeated treatments with bortezomib (Velcade) for relapsed multiple myeloma are safe and effective, and are not associated with new or cumulative toxicities

ORLANDO—Repeated treatments with bortezomib (Velcade) for relapsed multiple myeloma are safe and effective, and are not associated with new or cumulative toxicities, according to posters presented at the 48th Annual Meeting of the American Society of Hematology.

"The efficacy and safety of single-agent bortezomib in relapsed multiple myeloma are well established. It is reassuring to know that using bortezomib again in this setting is also safe and effective, and can improve disease outcomes even in patients who did not respond to their first treatment of Velcade," said Roy Beveridge, MD, of Inova Fairfax Hospital, Falls Church, Virginia.

Dr. Beveridge and lead author Therese M. Conner, PhD, of US Oncology, Houston, presented the results of an observational, retrospective analysis of 94 relapsed multiple myeloma patients who were identified from the US Oncology database (abstract 3531). The patients had received at least two bortezomib-based treatments between May 2003 and November 2005, and there was a gap of at least 60 days between each treatment.

During their first treatment, the patients received a median of 16 doses of bortezomib and in their second treatment, a median of 12 doses. The median time between the first and second bortezomib treatment was 5 months (range, 2 to 17 months). Of note, two patients in each treatment period received more than 60 bortezomib doses. The majority (55%) received single-agent bortezomib without intervening therapies between their first and second bortezomib treatment.

In response to initial therapy, 57% of patients achieved a partial response or better. When these patients were treated again with bortezomib, 32% achieved at least a partial response. Of all patients in the analysis, an overall response rate of 20% was achieved with retreatment, regardless of their initial response.

The most common toxicities were neuropathy and thrombocytopenia. Interestingly, noted the investigators, discontinuation of treatment due to neuropathy decreased from 17% on initial treatment to 5% on retreatment.

Patients From Three Studies

In another retrospective analysis of bortezomib retreatment for patients with relapsed multiple myeloma, Jeffrey Lee Wolf, MD, Alta Bates Comprehensive Cancer Center, Berkeley, California, and colleagues reported similar results suggesting that repeated treatment may prolong disease control, even when patients have failed to respond to initial bortezomib treatment (abstract 3532).

They reviewed the records of 22 patients from the SUMMIT, CREST, and APEX registration studies who received retreatment with bortezomib off protocol. Prior to their initial bortezomib-based treatment, these patients had received a median of 3.5 therapies; initial bortezomib produced an overall response rate of 68%. For retreatment, patients received bortezomib for a median of 3.8 months in 5.5 cycles. Most received bortezomib in combination with one or more other agents or radiation therapy.

Of the 15 patients who responded to initial bortezomib, 9 (60%) responded to retreatment. Of the 7 patients who did not respond to their first bortezomib treatment, 2 (29%) responded to retreatment. This was likely due to either longer treatment or the addition of a second agent, Dr. Wolf reported.

No patients required a dose reduction due to peripheral neuropathy during retreatment, compared with four patients who required a dose reduction during their initial treatment. "If the patient had significant neuropathy on initial bortezomib treatment," he said, "we dose reduced for retreatment and hence had fewer occasions when we had to dose reduce further or stop therapy."

Terminating therapy because of toxicity was similar during initial and retreatment phases. Three patients required hospitalization for toxicity during their initial treatment with bortezomib, but no patients needed to be hospitalized during retreatment.

"Velcade retreatment makes sense because initially, we usually don't treat to drug failure; combinations with Velcade are often synergistic; and with careful attention to dosing and dose adjustment, toxicities can be reduced the second time around," Dr. Wolf said.