A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma.

Laubach, Jacob P.; Moslehi, Javid J.; Francis, Sanjeev A.; San Miguel, Jesús F.; Sonneveld, Pieter; Orlowski, Robert Z.; Moreau, Philippe; Rosiñol, Laura; Faber, Edward A.; Voorhees, Peter; Mateos, Maria ‐ Victoria; Marquez, Loreta; Feng, Huaibao; Desai, Avinash; Velde, Helgi; Elliott, Jennifer; Shi, Hongliang; Dow, Edward; Jobanputra, Nishith; Esseltine, Dixie ‐ Lee

This retrospective analysis aimed to establish the overall cardiac safety profile of bortezomib using patient-level data from one phase 2 and seven phase 3 studies in previously untreated and relapsed/refractory multiple myeloma ( MM). Seven clinically relevant primary [congestive heart failure ( CHF), arrhythmias, ischaemic heart disease ( IHD), cardiac death] and secondary (hypertension, dyspnoea, oedema) cardiac endpoints were defined based on Med DRA v16.0 preferred terms. 2509 bortezomib-treated patients and 1445 patients in non-bortezomib-based control arms were included. The incidence of grade ≥3 CHF was 1·3-4·0% in studies in relapsed/refractory MM and 1·2-4·7% in previously untreated MM (2·0-7·6% all grades), with no significant differences between bortezomib- and non-bortezomib-based arms in comparative studies. Incidences of arrhythmias (1·3-5·9% grade ≥2; 0·6-4·1% grade ≥3), IHD (1·2-2·9% all grades; 0·4-2·7% grade ≥3) and cardiac death (0-1·4%) were low, with no differences between bortezomib-based and non-bortezomib-based arms. Higher rates of oedema (mostly grade 1/2) were seen in bortezomib-based versus non-bortezomib-based arms in one study and a pooled transplant study analysis. Logistic regression analyses of comparative studies showed no impact on cardiac risk with bortezomib-based versus non-bortezomib-based treatment. Bortezomib-based treatment was associated with low incidences of cardiac events.

BORTEZOMIB; MULTIPLE myeloma treatment; PROTEASOME inhibitors; RETROSPECTIVE studies; LOGISTIC regression analysis

British Journal of Haematology, 2017, Vol 178, Issue 4, p547

0007-1048

Academic Journal

10.1111/bjh.14708