With regard to the safety profile and toxicities, our study indicated that the rates of overall AEs and drug-related deaths or discontinuation from follow-up were similar in experimental and control groups. As stated earlier, similar frequencies of overall AEs and grades 3 and 4 PN were observed both in bortezomib-based and non-bortezomib-based groups. Cumulative meta-analysis showed that grades 3 and 4 PN was more frequent in bortezomib-containing consolidation therapy groups (with the duration of bortezomib being less than 6 months); however, no statistical significance was found for differences between the experimental and control groups when the maintenance treatment was added to the meta-analysis. This is in accordance with the result of a Phase III APEX trial in relapsed MM demonstrating that the neuropathy generally occurs in the first five cycles of bortezomib treatment, which is related to the accumulated dose; after the fifth cycle (with an accumulated dose of approximately 30 mg/m2), the incidence of neuropathy reaches a plateau, and increases since then by only 4% until the eighth and final cycle.27 Moreover, administration adjustment of bortezomib, such as dose reduction, once weekly regimen,28 and subcutaneous administration,29,30 might help to reduce the incidence and severity of neuropathy. Therefore, the results in the present study indicated that bortezomib-based post-transplantation treatment, especially maintenance, was well tolerated and the treatment-related risks did not appear to outweigh the benefits of treatment.

In recent years, some clinical trials (including the analyzed three RCTs) showed that the benefits of bortezomib consolidation and maintenance were more evident in patients who had not previously achieved at least VGPR;11 patients who achieved CR/nCR after their induction therapy have a tendency of getting better outcomes in terms of PFS and OS;31–33 cytogenetic abnormalities, such as t(4;14) and del(17p), might more or less influence the response and outcome of bortezomib treatment;34,35 however, due to lack of patient-level data, such associations could not be confirmed in this meta-analysis. In addition, the difference in patient characteristics, induction regimens, and the frequency of transplantation between the two groups could be potential confounding factors interfering with the interpretation of our studies. Therefore, more qualified data or RCTs are required to confirm our analysis.


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In conclusion, post-transplantation therapy (especially maintenance therapy) with bortezomib-based regimen contributes to improved response rate and PFS with a favorable safety profile. However, prolonged follow-up period is required to confirm the beneficial effect of bortezomib-based post-transplantation therapy conferred on OS.

Acknowledgment

This work was supported by the Research Fund from the National Natural Science Foundation of China (No 81272627).

Disclosure

The authors report no conflicts of interest.


Xiaoping Liu,1 Colin K. He,2 Xiangyu Meng,1 Li He,1 Kaili Li,1 Qing Liang,1 Liang Shao,1 Shangqin Liu1

1Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Orient Health Care, NYC, USA 


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