An Observational, Retrospective Analysis of Retreatment with Bortezomib of Mulitple Myeloma (MM) Patients.

BACKGROUND: The efficacy and safety of single agent bortezomib (btz) in relapsed MM is well established. In that setting, typically 8 cycles of therapy (6 months) are given and treatment stops. However, no therapy is curative and upon relapse, patients are more refractory to subsequent therapies. Until recently, there has been little information on the feasibility and benefits of retreatment with btz. This study was designed to assess the safety and efficacy of btz used as retreatment either as a single agent or in combination with other agents in community oncology practices.

METHODS: MM pts who received at least two btz-based therapies between May 2003 and November 2005 and who had a ≥60-day gap between each treatment were identified from 22 sites using the US Oncology electronic claims warehouse. Data were transcribed from the patient records to a prespecified case report form for analysis. Best response was determined using M-protein values when available: partial response (PR), 50–89% decrease; very good PR (VGPR) or better, ≥90% decrease. In some cases, physician assessments were available without laboratory confirmation in the chart.

RESULTS: Ninety-four patients with relapsed MM met the eligibility requirements. Mean age was 65.9 years, 43% were female, median time from diagnosis to initial btz treatment was 3 years, and median number of therapies prior to first btz treatment was three. Patients received a median of 16 btz doses during the first treatment and a median of 12 doses in the second treatment; the median time between first and second btz treatment was 5 months (range 2–17). Notably, two patients in each treatment period received over 60 btz doses. The majority (55%) of patients received single agent btz without intervening therapies between first and second btz treatment. Of patients evaluable for response, a PR or better was achieved in 44 of 78 (56%) patients in response to initial therapy (26% achieved a VGPR or better) and in 17 of 85 (20%) in response to retreatment. Of patients with a ≥PR, 12 of 39 (31%) responded upon retreatment. Nine percent of patients who did not respond initially achieved a PR when retreated. Of those who achieved a VGPR or better on initial treatment, 18% achieved at least a VGPR on retreatment. The number of patients who stopped treatment due to toxicity was lower with retreatment (27%) compared with initial treatment (39%). Neuropathy and thrombocytopenia were the most common toxicities leading to discontinuation; treatment discontinuation due to neuropathy decreased from 17% on initial treatment to 5% on retreatment. Nine patients received ≥2 btz retreatments.

CONCLUSIONS: Data from the US Oncology claims database for 94 patients retreated with btz (more than two retreatments in some) suggest that retreatment is safe and effective and not associated with new or cumulative toxicities. Btz is an option for repeated therapy in relapsed patients.