Abstract

In myeloma therapy retreatment after successful therapy is frequently considered. Here we present pooled data from a German and Swiss multicenter, retrospective survey (26866138MMY4014). The survey started in Germany and was later extended to Switzerland. German data have already been published before. Here we report on the entire cohort of patients for the first time.

For inclusion into this analysis, patients with MM had to have had preceding bortezomib treatment, resulting in at least partial remission and a second therapy with Bortezomib on relapse. The intention of this trial was to provide further evidence of the value of a retreatment with bortezomib, description of predisposing factors and comparison of response quality and remission duration in this predefined patient group of bortezomib responders. Data from 36 centers and 94 patients were available for safety analysis. 34 patients had to be excluded from the efficacy analysis due to major deviations from the inclusion criteria, i.e. concomitant antineoplastic treatment, retreatment with bortezomib not being completed, no response during initial bortezomib treatment or missing information about MM-specific interim therapy. Thus 60 patients were left for the per protocol population (PP). Patients had a mean age of 65.5 years (40–89), 56.4% being male. Patients had received a mean of 3.7 prior therapies for multiple myeloma before initial bortezomib therapy, most frequently melphalan-prednisone (44.7%), dexamethasone (38.3%) and/or vincristine-adriamycin-dexamethasone (31.9%). Stem cell transplantation was undertaken in 26.6% of the patients.

Mean cycle numbers for initial bortezomib therapy and retreatment were 5.8 and 4.5, respectively. The majority of patients (85.1% and 78.7%, respectively) received a bortezomib dose of 1.3 mg/m2. Concomitant dexamethasone therapy was administered to 43.6% and 62.8% of the patients, respectively. Between the initial bortezomib therapy and bortezomib retreatment 13.8% of the patients received other MM-specific interim therapy.

The efficacy analysis was based on the PP population and revealed very encouraging responses. Overall response (OR) was defined as complete response (CR), nearly complete response (nCR) and partial response (PR). With a pre-defined OR of 100% for the initial bortezomib therapy, 63% (49.9–75.4%) responded again to retreatment. Best response is summarized in the table below.

Subgroup analyses of the rates of clinical benefit (CR, nCR, PR or SD) were performed by treatment free interval (TFI) after initial bortezomib therapy (<= 6 months versus > 6 months) and by concomitant dexamethasone treatment. In patients with TFI > 6 months a higher rate of clinical benefit (89.7%) could be achieved as compared to TFI <= 6 months (61.9%). Concomitant dexamethasone treatment was associated with a lower rate of clinical benefit (76.5%) than without (84.6%).

For 44 patients (46.8%) a total of 125 adverse drug reactions (ADRs) were documented. 21 serious ADRs were documented in 11 (11.7%) patients. 30 patients had died at the time of analysis. 2 patients died due to adverse events (pneumonia and pulmonary oedema) assessed as at least possibly related to bortezomib. For one fatal outcome (pneumonia) causality assessment has not been provided.

This binational retrospective survey suggests that the safety profile is in line with the current summary of product characteristics of Velcade and that high remission rates and durable TFIs can be achieved by bortezomib retreatment. A TFI > 6 months could be a good clinical marker for a higher rate of clinical benefit. Results of an ongoing prospective trial on bortezomib retreatment are awaited to confirm these results.

 Initial bortezomib therapy (N=60) Bortezomib retreatment (N=60) 
* based on n=47 patients responding to bortezomib retreatment. 
Complete response (CR) 12 (20%) 8 (13.3%) 
Nearly complete response (nCR) 7 (11.7%) 3 (5%) 
Partial response (PR) 41 (68.3%) 27 (45%) 
Stable disease (SD) - (not allowed by selection criteria) 10 (16.7%) 
Progressive disease (PD) - (not allowed by selection criteria) 12 (20%) 
Median time to response 3.1 months 3.3 months* 
Median duration of response 6.9 months 6.1 months* 
Median treatment free interval 8.6 months 5.7 months 
 Initial bortezomib therapy (N=60) Bortezomib retreatment (N=60) 
* based on n=47 patients responding to bortezomib retreatment. 
Complete response (CR) 12 (20%) 8 (13.3%) 
Nearly complete response (nCR) 7 (11.7%) 3 (5%) 
Partial response (PR) 41 (68.3%) 27 (45%) 
Stable disease (SD) - (not allowed by selection criteria) 10 (16.7%) 
Progressive disease (PD) - (not allowed by selection criteria) 12 (20%) 
Median time to response 3.1 months 3.3 months* 
Median duration of response 6.9 months 6.1 months* 
Median treatment free interval 8.6 months 5.7 months 

Disclosures: Voegeli:Janssen-Cilag: Honoraria. Taverna:Janssen-Cilag: Membership on an entity’s Board of Directors or advisory committees. Olie:Janssen-Cilag: Employment. Pliskat:Janssen-Cilag: Employment. Frohn:Janssen-Cilag: Employment.

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