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Clinical Trial
. 2014 Jun 26;123(26):4136-42.
doi: 10.1182/blood-2013-12-546374. Epub 2014 May 15.

Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma

Jesús San-Miguel  1 , Joan Bladé  2 , Ofer Shpilberg  3 , Sebastian Grosicki  4 , Frédéric Maloisel  5 , Chang-Ki Min  6 , Marta Polo Zarzuela  7 , Tadeusz Robak  8 , Sripada V S S Prasad  9 , Yeow Tee Goh  10 , Jacob Laubach  11 , Andrew Spencer  12 , María-Victoria Mateos  13 , Antonio Palumbo  14 , Tom Puchalski  15 , Manjula Reddy  15 , Clarissa Uhlar  15 , Xiang Qin  15 , Helgi van de Velde  16 , Hong Xie  15 , Robert Z Orlowski  17
Affiliations
Clinical Trial

Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma

Jesús San-Miguel et al. Blood. .

Erratum in

  • Blood. 2014 Aug 14;124(7):1201

Abstract

Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P = .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859.

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Figures

Figure 1
Figure 1
Kaplan-Meier plot of PFS in the randomized intention-to-treat population. Numbers on the x-axis represent days.
Figure 2
Figure 2
Median serum concentration for CRP by study visit in the randomized intention-to-treat population. C, cycle; D, day.
See this image and copyright information in PMC

References

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    1. San Miguel JF, Schlag R, Khuageva N, et al. Phase 3 VISTA trial, after 5 years' follow-up, demonstrates a persistent significant overall survival benefit with bortezomib-melphalan-prednisone versus melphalan-prednisone, and no increased risk of second primary malignancies, in patients with previously untreated multiple myeloma. J Clin Oncol. 2013;31(25):448–455. - PubMed
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