Effective response with bortezomib retreatment in relapsed multiple myeloma – a multicentre retrospective survey in Switzerland

Abstract

Previous studies have shown that retreatment of relapsed/refractory multiple myeloma (MM) with a second course of bortezomib therapy could be effective in heavily pre-treated patients. In this study, the results of a multicentre, retrospective survey were reported involving patients in Switzerland with MM who responded to initial bortezomib therapy; 43 patients were enrolled and 42 were evaluated for response. The overall response rate (complete response [CR] + near CR [nCR] + partial response [PR]) to bortezomib retreatment was 64.3%, and the clinical benefit rate (CR + nCR + PR + stable disease) for retreatment was 83%. The response rate to bortezomib retreatment in the subgroup with a first treatment-free interval (TFI) >6 months was higher than that in the subgroup with first TFI ≤6 months (74.1% vs. 46.7%) and lower in patients who received concomitant dexamethasone with bortezomib retreatment (57.1% vs. 78.6%). The median overall survival (OS) from first diagnosis of MM was 9.3 years, and after retreatment with bortezomib the median OS was 1.7 years. In total, 85.7% of patients who achieved CR or nCR with initial bortezomib treatment achieved CR or nCR with retreatment. Bortezomib as retreatment was well tolerated, and the safety profile was consistent with previous studies of bortezomib in relapsed MM. The most common adverse drug reaction attributed to bortezomib was peripheral neuropathy in 5 patients. In conclusion, bortezomib retreatment was a well-tolerated, effective therapeutic option for relapsed MM patients in the Swiss clinical setting who have previously responded to bortezomib, particularly for those who experienced an initial TFI of >6 months.

Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma

“…All primary na€ ıve patient samples analyzed (nD5 /5) showed significantly reduced cell viability in response to bortezomib in vitro, while the majority (nD4 /6) of primary relapsed samples showed no significant reduction in viability. The remaining (nD2 /6) primary relapsed samples showed significantly decreased cell viability in response to bortezomib, in-keeping with the clinical observation that approximately half of patients retreated with bortezomib will respond again 30,31 (Fig. 1D).…”

“…Single agent bortezomib has a response rate of approximately 30% but, when used in combination with chemotherapy and/ or corticosteroids, response rates range from approximately 60% to over 90% depending on the regimen. 16 Despite this relative success, however, clinical relapse following bortezomib therapy presently remains inevitable and resistance to further bortezomib treatment is common, 30,31 not only as a consequence of, but also further driving the selection and emergence of drug-resistant clones. 7,8 An improved understanding of the mechanisms underlying bortezomib-resistance is, therefore, vital for the progressive development of novel pharmacologic strategies to overcome the clinical phenomenon of bortezomib-resistance.…”

Treatment of relapsed and refractory multiple myeloma

“…Trials and retrospective analyses have shown that retreatment with bortezomib is feasible and effective and does not incur cumulative toxicity. [50][51][52] Lenalidomide retreatment is also feasible and may induce responses in up to 44 % of relapsed patients, and is better than retreatment with thalidomide. 51,53 Tolerability is another important consideration, and factors like neuropathy, myelosuppression and thrombosis may influence the choice of therapy.…”

“…54 If an effective alternative treatment is available at relapse, switching drug class is preferable, while previously used agents may then be considered in later lines. 29,50 Patients may even become sensitive to (escalated dosages of) drugs to which they were previously refractory, based on the appearance of different tumor clones during subsequent stages of the disease.…”

Replacement of bortezomib with carfilzomib for multiple myeloma patients progressing from bortezomib combination therapy

“…7 The success achieved following retreatment of patients with bortezomib has occurred in specific clinical settings. Bortezomib retreatment has been successful for some patients that were previously responsive to this PI, [8][9][10] and for relapsed and refractory MM patients treated with it in combination with other anti-MM agents. 11,12 The ability to overcome bortezomib resistance following retreatment with a different PI has been demonstrated in preclinical studies with bortezomib, carfilzomib, oprozomib (ONX 0912), ixazomib (MLN 9708), delanzomib (CEP-18770) and MLN 2238.…”