Utility of Bortezomib Retreatment for Patients with Relapsed Multiple Myeloma.
Authors: Wolf Jeffrey Lee , Richardson Paul , Schuster Michael , LeBlanc Annette , Battleman David , Walters Ian 
Published: October 2019

Abstract
Bortezomib (VELCADE®; Vc) has become the standard of care for patients with relapsed multiple myeloma (MM). Generally, therapies to treat MM are used sequentially, and are not typically repeated. Unlike most other therapies, which treat until progression, treatment with Vc follows a specified time-course (~8 cycles). Thus, bortezomib may be an ideal candidate for repeat therapy, although its utility in this setting has not yet been determined. This retrospective case series was designed to clarify the utility of Vc as a repeat therapy. We reviewed the records of patients from the phase 2 (SUMMIT and CREST) and 3 (APEX) registration studies who were subsequently retreated off protocol. Medical records review at 3 major cancer centers yielded 22 patients who completed Vc retreatment following at least a 60 day treatment free interval. This sample had the following demographics: median age of 60, isotypes IgG 68%, IgA 13.6%, IgD 4.5%, and light chain 9.0%; 55% were female. Patients had had a median of 3.5 therapies prior to their initial Vc treatment. Retreatment occurred as a median 6th line of therapy. Patients were determined to have responded to treatment if the greatest mean reduction in serum/urine M-protein or bone marrow plasma cells was >50%. During initial Vc therapy, patients received a median of 4.9 months (7.5 cycles) of Vc treatment and the response rate was 68% (15/22) to Vc alone or Vc plus dexamethasone. The median treatment-free interval was 12.6 months between the end of the first Vc treatment and the next MM treatment (range 2 weeks to 45 months). For 55% of these patients (12/22), treatment following relapse after the first Vc treatment was with a different agent or combination of agents. Retreatment with Vc was typically part of combination therapy and lasted a median of 3.8 months (5.5 cycles); 59% (13/22) added one or more of the following: dexamethasone, doxil, thalidomide, melphalan, decadron, and/or radiation therapy. Of the 15 patients who responded to the first Vc treatment, 9 (60%) responded to retreatment. Of the 7 patients who did not respond to the first Vc treatment, 2 (29%) responded to re-treatment. This was likely due to either longer treatment or the addition of a second agent. Overall, the Vc retreatment response rate was 50% (11/22). During retreatment, no patients experienced a dose reduction due to peripheral neuropathy, compared to 4 patients (2 with grade 2 and 2 with grade 3) during initial treatment. Termination of therapy due to any unmanageable toxicity was similar during both initial and retreatment. Finally, no patients were hospitalized for Vc-related adverse events during retreatment, while 3 patients had been hospitalized during initial treatment. On the basis of these data, Vc retreatment appears to be safe and effective, yielding high clinical response rates and low rates of toxicity and/or hospitalization. Although the numbers of patients in this study are small, the observed patterns are instructive; the data reported here suggest that repeated treatment with Vc may result in prolonged disease control, even if the patient had failed to respond to the first treatment with Vc. Additional prospective trials are ongoing.