Original Article

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Blood Res 2013; 48(3):

Published online September 25, 2013

https://doi.org/10.5045/br.2013.48.3.198

© The Korean Society of Hematology

The impact of novel therapeutic agents before and after frontline autologous stem cell transplantation in patients with multiple myeloma

Chang-Ki Min*, Sung-Eun Lee, Seung-Ah Yahng, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, and Chong-Won Park

Hematology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.

Correspondence to : Correspondence to Chang-Ki Min, M.D., Ph.D. Hematology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpodaero, Seocho-gu, Seoul 137-701, Korea. Tel: +82-2-2258-6053, Fax: +82-2-599-3589, ckmin@catholic.ac.kr

Received: February 20, 2013; Revised: April 1, 2013; Accepted: July 12, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Novel agents (NAs) such as thalidomide and bortezomib have been administered in combination with autologous stem-cell transplantation (ASCT) to effectively treat multiple myeloma (MM). However, whether NAs perform better as induction treatments prior to transplantation, or as post-transplant maintenance therapies remains unclear.

Methods

We retrospectively analyzed 106 consecutive patients with MM who underwent ASCT within 1 year of diagnosis as first-line therapy.

Results

Eighty-seven (82.1%) patients received NAs before ASCT, whereas 68 (64.2%) received NAs after ASCT. NAs were administered to each patient as follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT were significantly higher for patients who received NAs as induction treatment compared to those who did not receive pre-transplant NAs. At a median follow-up of 37.9 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and P=0.04, respectively), but not in those with NAs as pre-transplant induction treatment. The PFS of patients with NAs before and after ASCT was higher than that of the patients with NAs as induction therapy alone (P=0.05). Age, serum β2-microglobulin level, complete response after ASCT, and NA use post-ASCT independently predicted survival outcomes.

Conclusion

These findings suggest that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT. Induction therapy using NAs also improves high-quality response rates before and after ASCT.

Keywords Multiple myeloma, Novel agents, Autologous stem cell transplantation, Induction and maintenance treatment

Article

Original Article

Blood Res 2013; 48(3): 198-205

Published online September 25, 2013 https://doi.org/10.5045/br.2013.48.3.198

Copyright © The Korean Society of Hematology.

The impact of novel therapeutic agents before and after frontline autologous stem cell transplantation in patients with multiple myeloma

Chang-Ki Min*, Sung-Eun Lee, Seung-Ah Yahng, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, and Chong-Won Park

Hematology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.

Correspondence to: Correspondence to Chang-Ki Min, M.D., Ph.D. Hematology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpodaero, Seocho-gu, Seoul 137-701, Korea. Tel: +82-2-2258-6053, Fax: +82-2-599-3589, ckmin@catholic.ac.kr

Received: February 20, 2013; Revised: April 1, 2013; Accepted: July 12, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Novel agents (NAs) such as thalidomide and bortezomib have been administered in combination with autologous stem-cell transplantation (ASCT) to effectively treat multiple myeloma (MM). However, whether NAs perform better as induction treatments prior to transplantation, or as post-transplant maintenance therapies remains unclear.

Methods

We retrospectively analyzed 106 consecutive patients with MM who underwent ASCT within 1 year of diagnosis as first-line therapy.

Results

Eighty-seven (82.1%) patients received NAs before ASCT, whereas 68 (64.2%) received NAs after ASCT. NAs were administered to each patient as follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT were significantly higher for patients who received NAs as induction treatment compared to those who did not receive pre-transplant NAs. At a median follow-up of 37.9 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and P=0.04, respectively), but not in those with NAs as pre-transplant induction treatment. The PFS of patients with NAs before and after ASCT was higher than that of the patients with NAs as induction therapy alone (P=0.05). Age, serum β2-microglobulin level, complete response after ASCT, and NA use post-ASCT independently predicted survival outcomes.

Conclusion

These findings suggest that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT. Induction therapy using NAs also improves high-quality response rates before and after ASCT.

Keywords: Multiple myeloma, Novel agents, Autologous stem cell transplantation, Induction and maintenance treatment

Fig 1.

Figure 1.

Patient disposition. Abbreviations: G-CSF, granulocyte colony-stimulating factor; PBPC, peripheral blood progenitor cell; VAD, vincristine, doxorubicin, and dexamethasone.

Blood Research 2013; 48: 198-205https://doi.org/10.5045/br.2013.48.3.198

Fig 2.

Figure 2.

(A) Progression-free survival according to novel agent use. (B) Overall survival according to novel agent use. Abbreviations: ASCT, autologous stem-cell transplantation; NAs, novel agents; PFS, progression-free survival; OS, overall survival.

Blood Research 2013; 48: 198-205https://doi.org/10.5045/br.2013.48.3.198

Fig 3.

Figure 3.

Kaplan-Meier curves for progression-free survival and overall survival according to the treatment time of novel agents. Abbreviations: ASCT, autologous stem-cell transplantation; NAs, novel agents; OS, overall survival; PFS, progression-free survival.

Blood Research 2013; 48: 198-205https://doi.org/10.5045/br.2013.48.3.198

Fig 4.

Figure 4.

Influence of response (≥VGPR vs. <VGPR) obtained after induction therapy on (A) progression-free survival (PFS) and (B) overall survival (OS); Influence of response (≥CR vs. <CR) obtained after transplantation on (C) PFS an (D) OS. Abbreviations: CR, complete response; VGPR, very good partial response.

Blood Research 2013; 48: 198-205https://doi.org/10.5045/br.2013.48.3.198

Table 1 . Patient characteristics according to treatment type..

Abbreviations: ASCT, autologous stem-cell transplantation; NAs, novel agents..


Table 2 . Response rates during pre- (A) and post-transplantation (B)..

Abbreviations: ASCT, autologous stem-cell transplantation; CR, complete response; NAs, novel agents; PR, partial response; VGPR, very good partial response..


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