Bortezomib-Based Induction Treatment for Patients with Multiple Myeloma Ineligible for Autologous Stem Cell Transplantation: A Retrospective Multicenter Study in Czech Republic

Background: Bortezomib- based induction is one of the most effective treatment options in the treatment of newly diagnosed and relapsed or refractory multiple myeloma (MM) patients. The aim of this analysis was to identify the best bortezomib regimen and identify factors associated with better or worse treatment response.

Patients and methods: Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic for 794 MM patients enrolled from June 2005 to January 2017. Median patient age was 70 years (56.0- 81.0), median number of delivered bortezomib cycles was 8 (4.0- 12.0). In total, 82% (651/794) of patients were treated bortezomib-based triplet combinations. Assessment of therapeutic response was possible in 87% (691/794) of treated patients. Evaluation of treatment response was performed according to the IMWG criteria.

Results: After a median follow up of 23 months (range 1.5- 129), overall response (ORR) was observed in 69.2% (478/691) patients, including 9.4% complete response (CR) and 34.7% very good partial response (VGPR). The regimen BMP (bortesomib-melphalan-prednisone) was the most effective among the three-mode regimens compared with the CBD (cyclophosphamide-bortezomib-dexamethasone), BDD (bortezomib-doxorubicin-dexamethasone) and BDD (bortezomib-thalidomide-dexamethasone) regimens. Median overall survival (OS) was (49 vs. 41.7 vs. 37.9 vs. 32.2 months, respectively), median time to progression (TTP) was (20.5 vs. 16 vs. 13.5 vs. 13.8 months, respectively) and median progression- free survival (PFS) was (22.3 vs. 18.5 vs. 13.7 vs. 13.8 months, respectively). The most frequent grade ≥ 3 toxicities were anemia in 17.5% and infections in 18% of patients. Peripheral neuropathy grade ≥ 2 was present in 21.3% of patients with no significant differences between regimens. In univariate analysis, factors significantly associated with worse ORR were as follows: calcium level > 2.9 mmol/l (OR 2.8 [95% CI: 1.6 - 4.9]; p< 0.001), M - protein concentration ≥ 23 g/l (OR 1.7 [1.2-2.4]; p= 0.001), level of lactate dehydrogenase > 2.8 μkat/l (OR 1.6 [1.1-2.3]; p= 0.017), male gender (OR 1.5 [1.1-2.1]; p= 0.012) and intravenous application of bortezomib (OR 1.6 [1.1-2.3]; p= 0.017).

Conclusions: We conclude that regimen VMP of the bortezomib-based triplet regimens was the most effective treatment option for MM patients ineligible for autologous transplantation. A detailed analysis will be the subject of communication.