Autografting

Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT

Abstract

The aims of this study were to investigate the outcomes of second salvage auto-SCT and to identify the impacts of a second auto-SCT compared with systemic chemotherapy alone on disease outcome. Data from 48 patients who underwent second auto-SCT were matched to 144 patients (1:3) who received systemic chemotherapy alone from the Korean Myeloma Registry. Groups were matched for nine potential prognostic factors and compared for treatment outcomes. The median age of matching-pairs at relapse was 55.5 years. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone induction therapy before the first auto-SCT. Thirty-five patients (73%) in the second auto-SCT group received novel agent-based therapies before the second auto-SCT, and similar proportion in both groups received novel therapies after relapse of front-line auto-SCT. With a median follow-up of 55.3 months, patients who underwent a second auto-SCT had significantly better median OS (55.5 vs 25.4 months, P=0.035). In multivariate analysis for OS, <18 months time to progression after first auto-SCT, International Staging System III and salvage chemotherapy alone were independent predictors for worse OS. The outcomes of second auto-SCT appear to be superior to those of systemic chemotherapy alone. A randomized trial comparing both treatment strategies is required.

Introduction

High-dose therapy with auto-SCT has been a standard of care for multiple myeloma in patients <65 years.1, 2 However, nearly all patients who undergo front-line auto-SCT will relapse and require further salvage therapy. Although salvage systemic chemotherapy,3, 4, 5, 6 second auto-SCT7, 8, 9, 10, 11, 12 and allo-SCT13, 14 are potential therapeutic options to address this issue, optimal treatment strategies for patients with multiple myeloma whose disease has relapsed after auto-SCT have not been established.

Several reports that focused on second salvage auto-SCT after relapse of front-line auto-SCT have been published.7, 8, 9, 10, 11, 12, 15, 16 These studies demonstrated that second salvage auto-SCT was feasible and reasonably effective. In particular, several studies suggested that the time to progression (TTP) after first auto-SCT or interval between transplants is an important predictor of the outcome of second auto-SCT.7, 8, 10, 11, 16 However, these studies have been criticized because of their small sample sizes. Furthermore, the lack of a control arm in these studies prevented exploration of the optimal treatment strategies for relapsed multiple myeloma. Recently, the introduction of novel agents such as thalidomide, lenalidomide and bortezomib has significantly changed the clinical outcomes of patients with multiple myeloma. There is emerging evidence suggesting that novel agent-based systemic chemotherapy may be effective for treating relapsed patients.3, 4, 5, 6 Therefore, further studies comparing these different treatment strategies that incorporate novel agents in salvage setting are required. A prospective randomized trial is required to compare different therapies such as second auto-SCT or systemic chemotherapy for relapsed multiple myeloma. However, to date, no prospective studies have been conducted.

Thus, our aims in this study were to investigate the outcomes of second salvage auto-SCT in patients who relapsed after front-line auto-SCT and to identify the impacts of second auto-SCT compared with salvage systemic chemotherapy alone. To minimize the heterogeneity between two treatment groups, we adopted a matched-pair design using a nationwide database.

Materials and methods

Study design and patients population

This study was conducted using the web-based ‘Korean Myeloma Registry (KMR)’ database of the Korean Multiple Myeloma Working Party (www.myeloma.or.kr). By 2010, a total of 4915 patients diagnosed with multiple myeloma between 1998 and 2010, had been registered in the KMR database. We identified 1146 patients who underwent front-line auto-SCT following induction chemotherapy from the KMR database. Of these, 49 patients who underwent second auto-SCT after relapse of front-line auto-SCT were included in the study cohort (Figure 1).

Figure 1
figure1

Study population. auto=autologous; allo=allogeneic.

The goal of this study was to perform a matched-pair analysis, each patient who underwent a second salvage auto-SCT was matched with 3 patients from a cohort of 517 patients treated with systemic chemotherapy alone after relapse of prior auto-SCT using the KMR database. The patients were matched for nine potential prognostic factors: age at relapse (<60 vs 60 years), serum creatinine level at diagnosis (<2 vs 2 mg/dL), the International Staging System (ISS; I vs II vs III), serum lactate dehydrogenase level (normal vs elevated), conventional cytogenetics (standard-risk vs high-risk), induction therapy at first auto-SCT (conventional cytotoxic agents vs novel agents), conditioning regimen at first auto-SCT ( high-dose melphalan 140 mg/m2 (MEL140) vs >MEL140), response to front-line auto-SCT ( very good PR vs < very good PR) and TTP after first auto-SCT (18 vs >18 months). Conventional cytogenetic results at diagnosis were grouped as high-risk and standard-risk groups. The high-risk cytogenetics indicated del(13q) or hypodiploidy, and standard-risk included all other cytogenetic results, including normal karyotype and hyperdiploidy. At least eight of these factors were required to match between the four matched patients. Records of matching controls were carefully reviewed and each institution was requested to provide the data for patients using additional study-specific case report forms. Suitable matching controls for one patient in the study cohort could not be found using these criteria, and this patient was therefore excluded from the analysis. A total of 48 groups of four patients met the matching criteria. Finally, 192 patients were selected for this analysis. Definitions of response were based on the International Myeloma Working Group uniform response criteria.17 This study protocol was reviewed and approved by the institutional review board of each participating institution.

Statistical analysis

The primary end points were PFS and OS. Survival end points were calculated from the first day of second-line therapy after relapse until progression, death or last follow-up, as appropriate. TTP after first auto-SCT was defined from the first day of stem cell infusion during the first auto-SCT to the date of progression. PFS and OS were estimated by the Kaplan–Meier method, and comparisons between groups were made using the log-rank test. Clinical variables were compared using Pearson’s χ2-test or Fisher’s exact test for categorical variables, and the Mann–Whitney test for continuous variables. Multivariate analysis was carried out using the Cox proportional hazards models. Variables with P<0.05 in univariate analyses were included in the multivariate model. The results were reported with a hazard ratio (HR) and 95% confidence interval (CI). P<0.05 was considered to reflect statistical significance. All statistical analyses were performed using SPSS for Windows, version 18.0 (SPSS Inc., Chicago, IL, USA).

Results

Patient characteristics and clinical findings of front-line auto-SCT

Forty eight patients who underwent a second salvage auto-SCT were compared with 144 patients treated with salvage systemic chemotherapy alone using a matched-pair method. Baseline patient and clinical characteristics related to the two groups are summarized in Table 1. The median age of matching-pairs of patients at relapse was 55.5 years (range, 33.4–68.5), and 106 patients (55%) were male. The ISS at diagnosis was III in 54 patients (28%), serum lactate dehydrogenase level was elevated in 133 patients (69%) and serum creatinine level was 2.0 mg/dL or more in 35 patients (18%). Conventional cytogenetic data were available for 156 patients (79%, Table 1). Of these, 18 patients (21%) were classified as high-risk. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone (VAD) induction therapy before the first auto-SCT. Stem cell source was peripheral blood stem cells in all patients. The main conditioning high-dose regimen was 200 mg/m2 of MEL200 in 179 patients (93%). Only 1 of 48 patients treated with second auto-SCT received <140 mg/m2 of MEL. Median interval between diagnosis and first transplantation was 5.9 months (range, 3.3–25.4 months), and this was not significantly different between two groups. After first auto-SCT, maintenance therapy was given to 56 patients (29%), of whom 38 (20%) received thalidomide±dexamethasone for a maximum of 14 months.

Table 1 Baseline patient and clinical characteristics

Information about front-line therapy response status was available in all patients. The response to front-line therapy was 67 CR (35%), 39 very good PR (20%), 68 PR (35%), 13 stable disease (7%) and 5 progressive disease (3%). The overall response rate after front-line auto-SCT was 90%. The median TTP after first auto-SCT was 12.0 months (range, 1.1–83.8 months). Fifty-seven patients (30%) had 18 months or more of TTP after first auto-SCT.

We found that our matching process was successful; the distribution of nine matching variables and unmatched other variables (Eastern Cooperative Oncology Group performance status, hypercalcemia and osteolytic bone lesions) was balanced between the two groups.

Salvage therapy after relapse of the first auto-SCT

The regimens of induction therapy before second auto-SCT and second-line therapy in the systemic chemotherapy-alone group are listed in Table 2. Before second salvage auto-SCT, 20 patients (42%) received induction therapy with bortezomib/dexamethasone (±doxorubicin), 12 (25%) received thalidomide/dexamethasone (±MEL or cyclophosphamide), 3 (6%) received bortezomib/thalidomide/dexamethasone (±cyclophosphamide) and 13 (27%) received non-bortezomib and non-thalidomide-based regimens. Second-line therapy in the systemic chemotherapy-alone group included bortezomib/dexamethasone (±doxorubicin) in 75 patients (52%), thalidomide/dexamethasone (±MEL or cyclophosphamide) in 37 (26%), bortezomib/thalidomide/dexamethasone (±cyclophosphamide) in 5 (3%) and non-bortezomib and non-thalidomide-based regimens in 27 (19%). Regimens given after relapse of front-line auto-SCT were similar between the two groups (P=0.447; Table 2).

Table 2 Regimens given after relapse of front-line auto-SCT and novel agents used in the salvage setting

For second auto-SCT, the majority of patients (45, 94%) received MEL200 as a conditioning therapy, whereas the remaining 3 patients received MEL with BU (2, 4%) or bortezomib (1, 2%). Only one treatment-related death occurred following second auto-SCT. This patient died because of sepsis 25 days after second auto-SCT.

Novel agents used in salvage therapy during the course of the disease were bortezomib in 151 patients (79%), thalidomide in 138 (72%) and lenalidomide in 6 (3%). A similar proportion of patients in both groups received bortezomib and lenalidomide. However, thalidomide was used more frequently in the systemic chemotherapy-alone group than in the second auto-SCT group (80% vs 58%, respectively; P=0.016; Table 2).

Treatment outcomes and analysis of prognostic factors

With a median follow-up of 55.3 months (range, 3.4–140.0 months), the median PFS and OS of the whole cohort were 11.4 months (95% CI, 9.0–13.8) and 35.4 months (95% CI, 24.3–46.5), respectively. In the second auto-SCT group, median PFS and OS were 18.0 months (95% CI, 15.2–20.8) and 55.5 months (95% CI, 46.2–64.8), respectively, and median PFS and OS in the systemic chemotherapy-alone group were 9.1 months (95% CI, 6.7–11.5) and 25.4 months (95% CI, 16.7–34.1), respectively. The PFS and OS of the second auto-SCT group were significantly better than those of the systemic chemotherapy-alone group (PFS, P=0.017; OS, P=0.035; Figures 2a and b, respectively).

Figure 2
figure2

Kaplan–Meier survival curve of (a) PFS and (b) OS according to second-line therapy (black solid line, the second salvage auto-SCT group; gray dashed line, the salvage systemic chemotherapy-alone group).

In univariate analysis for PFS, the ISS (P=0.001), serum β2-microglobulin level (P<0.001), serum creatinine level (P=0.038), response to front-line auto-SCT (P=0.026), TTP after first auto-SCT (P<0.001), conventional cytogenetics (P<0.001) and second-line therapy (P=0.017) were significantly associated with progression (Table 3). However, based on the multivariate analysis, 18 months of TTP after first auto-SCT (HR, 2.40; 95% CI, 1.56–3.69), high-risk cytogenetics (HR, 1.74; 95% CI, 1.14–2.67) and second-line chemotherapy alone (HR, 1.60; 95% CI, 1.04–2.46) were independent prognostic factors for shorter PFS (Table 4).

Table 3 Univariate analysis for PFS and OS
Table 4 Multivariate analysis of prognostic factors for PFS and OS

In univariate analysis for OS, the ISS (P<0.001), serum β2-microglobulin level (P<0.001), serum creatinine level (P=0.011), TTP after first auto-SCT (P<0.001), conditioning therapy at first auto-SCT (P=0.019), conventional cytogenetics (P=0.002) and second-line therapy (P=0.035) were significantly related to death (Table 3). However, in multivariate analysis, 18 months of TTP after first auto-SCT (HR, 2.77; 95% CI, 1.49–5.14), ISS III (HR, 2.04; 95% CI, 1.09–3.82) and second-line chemotherapy alone (HR, 1.88; 95% CI, 1.09–3.22) were independent prognostic factors for reduced OS (Table 4).

Based on the TTP after first auto-SCT and the ISS, patients were divided into two prognostic subgroups: a good prognosis subgroup and poor prognosis subgroup. The good prognosis subgroup was composed of patients who had TTP of >18 months after first auto-SCT and the ISS I or II, whereas the poor prognosis subgroup was composed of patients with a TTP of 18 months or less after first auto-SCT or ISS III. In an analysis of the good prognosis subgroup, OS was not different between the second auto-SCT group and the systemic chemotherapy-alone group (median, 75.3 vs 77.3 months, respectively; P=0.919), whereas in the poor prognosis subgroup, OS was significantly longer in the second auto-SCT group than the systemic chemotherapy-alone group (median, 49.9 vs 17.2 months, respectively; P=0.026; Table 5).

Table 5 Subgroup analysis according to TTP after first auto-SCT and ISS status

Effect of novel induction therapies before the second transplant

Among the 48 patients who underwent second auto-SCT, 35 patients received induction therapy using novel therapies before second auto-SCT. Induction therapies using novel agents before second auto-SCT failed to provide an OS benefit over conventional VAD-like induction therapies (median, 58.8 vs 52.5 months, respectively; P=0.110), although novel induction therapies approached statistical significance for longer PFS compared with conventional therapies (median, 18.6 vs 11.9 months, respectively; P=0.051). However, when the PFS and OS were compared in patients treated only with VAD-like conventional therapies before their first auto-SCT, patients that received novel induction therapies before second auto-SCT had a significantly better PFS than those that received conventional induction therapies (median, 19.3 vs 11.9 months; respectively; P=0.048) and showed a trend for longer OS (median, 58.8 vs 52.5 months, respectively; P=0.088).

Discussion

To address the impact of second auto-SCT in patients with multiple myeloma, we performed a matched-pair analysis at a ratio of 1:3 in a large series of patients. We chose this design to provide the highest level of evidence, because randomized trials comparing second auto-SCT to systemic chemotherapy alone have not been conducted. In this present analysis, we found that PFS and OS in patients who underwent second auto-SCT were superior to those of patients who received systemic chemotherapy alone, although fewer patients in the second auto-SCT group received thalidomide. Furthermore, second salvage auto-SCT was an independent predictor for survival. Approximately 80% of patients treated with systemic chemotherapy alone received bortezomib- or thalidomide-based therapies as second-line therapy. The survival outcomes of the salvage systemic chemotherapy-alone group, control arm in this study, support our findings. The international phase III trial of Assessment of Proteasome Inhibition for Extending Remission (APEX), which was conducted to compare bortezomib and dexamethasone in patients with relapsed multiple myeloma, of whom, 67% received prior auto-SCT, showed that bortezomib demonstrated superior efficacy to high-dose dexamethasone, with a median TTP and OS of 6.22 and 29.8 months, respectively.5, 6 Although direct comparison between these two studies is difficult, survival outcomes in our systemic chemotherapy-alone group were comparable to those in the APEX trial. Consequently, it might be interpreted that our control arm would represent the outcomes of relapsed patients treated with novel biologic agents. Therefore, our results might provide a substantial evidence favoring second auto-SCT in patients with multiple myeloma who have relapsed after front-line auto-SCT.

Although there are no specific guidelines, there is a general consensus that salvage auto-SCT can provide benefits to patients who show evidence of a durable response for at least 18 to 24 months after their first auto-SCT.18 However, an interesting finding in this study is that long-term remission after first auto-SCT is associated with favorable outcomes after relapse, irrespective of any kind of salvage therapy. Besides, our subgroup analysis revealed that survival benefit conferred by second salvage auto-SCT was more marked in patients with poor prognostic characteristics. These findings imply that TTP after first auto-SCT does not affect the choice of salvage therapy, but is simply a surrogate marker that reflects the biologic aggressiveness of the tumor. This idea is further supported by the previous observations of increasing survival after relapse with increasing duration of response to the front-line auto-SCT irrespective of subsequent therapies.19, 20, 21 This is quite different from the previous reports that salvage auto-SCT is of greater benefit in patients with long-term remission. Clearly, caution is required in interpreting our results and comparing them with previous series because of methodological differences. Considering the consistently favorable outcomes in patients with long TTP after first auto-SCT and the current low mortality of salvage auto-SCT, we agree that patients with long TTP after first auto-SCT could benefit from second salvage auto-SCT. However, we found that second salvage auto-SCT in patients with poor prognostic characteristics, that is, a TTP of <18 months after first auto-SCT or ISS III, also provided benefits. This finding can be explained by the characteristics of our study population. Approximately 80% of patients included in this study received conventional VAD-like induction chemotherapy before first auto-SCT and more than two-thirds of patients did not receive any maintenance therapy following first auto-SCT. These data suggest that a substantial proportion of patients included in our analysis underwent front-line auto-SCT without novel therapies. However, for induction therapy before second auto-SCT, >80% of patients received novel therapies, including bortezomib and thalidomide. Thus, these findings imply that the second auto-SCT may have been a more intensive therapy than the first auto-SCT. Potential synergy between novel induction therapies and high-dose therapy in patients with poor prognostic characteristics may account for better outcomes seen in patients who underwent second auto-SCT in our study. Actually, comparison of the outcomes of novel induction therapies and conventional VAD-like therapies before second auto-SCT in patients who received VAD-like conventional therapy for their first auto-SCT revealed that patients treated with novel induction therapies had a better OS than those treated with conventional VAD-like therapies, although the difference was not statistically significant (P=0.088). This concept is also supported by observations that novel induction therapies, especially bortezomib, before auto-SCT could overcome the poor prognosis associated with chromosomal changes.22, 23, 24, 25, 26 Therefore, these data suggest that second auto-SCT following short-course of novel induction therapies might be a reasonable option for overcoming the adverse prognosis or biologic aggressiveness of the tumors after relapse. Unfortunately, interphase FISH data were not available for the majority of cases in our study. Although del(13q) and hypodiploidy identified by conventional cytogenetic techniques were associated with worse PFS and OS, the outcomes of specific chromosomal abnormalities were not fully assessed in this study because of the extremely small number of patients with each abnormality. Therefore, prospective studies in larger populations are needed to validate the relationship between novel induction therapies before second auto-SCT and clinical outcomes and chromosomal changes. Nevertheless, our study suggests that second salvage auto-SCT following novel induction therapies might be effective in patients with multiple myeloma who have relapsed after front-line auto-SCT, especially those who received conventional induction therapies, irrespective of the presence of prognostic characteristics, such as early relapse after first auto-SCT and ISS III.

As with all other observational studies, our study has limitations. The present analysis is virtually based on retrospective data with a small number of patients and the choice of therapy after relapse is often governed by a complex list of unmeasured factors that can potentially affect outcomes. Although we adjusted for potential risk factors by a matched-pair analysis, only a randomized trial comparing second auto-SCT to systemic chemotherapy alone can exclude potential selection bias. In addition, although the median follow-up duration of our study was >4.5 years, late convergence between two groups in the Kaplan–Meier survival curve for OS is needed for further follow-up. Nonetheless, our study is the first to show the benefit of second salvage auto-SCT compared with systemic chemotherapy alone. Hence, further prospective studies are required to validate our observations and optimize treatment strategies to improve outcomes in patients who relapsed after front-line auto-SCT.

In conclusion, the outcomes of second salvage auto-SCT appear superior to those of systemic chemotherapy. In addition, second salvage auto-SCT was an independent predictor of better survival. Considering the low mortality associated with second auto-SCT, our results might provide substantial evidence for performing second auto-SCT after relapse and suggest the value of performing a prospective randomized trial comparing second auto-SCT and systemic chemotherapy alone in patients who relapsed after front-line auto-SCT.

References

  1. 1

    Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.

  2. 2

    Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

  3. 3

    Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357: 2123–2132.

  4. 4

    Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357: 2133–2142.

  5. 5

    Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352: 2487–2498.

  6. 6

    Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007; 110: 3557–3560.

  7. 7

    Jimenez-Zepeda VH, Mikhael J, Winter A, Franke N, Masih-Khan E, Trudel S et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transplant 2011; 18: 773–779.

  8. 8

    Olin RL, Vogl DT, Porter DL, Luger SM, Schuster SJ, Tsai DE et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Transplant 2009; 43: 417–422.

  9. 9

    Elice F, Raimondi R, Tosetto A, D'Emilio A, Di Bona E, Piccin A et al. Prolonged overall survival with second on-demand autologous transplant in multiple myeloma. Am J Hematol 2006; 81: 426–431.

  10. 10

    Fenk R, Liese V, Neubauer F, Bruns I, Kondakci M, Balleisen S et al. Predictive factors for successful salvage high-dose therapy in patients with multiple myeloma relapsing after autologous blood stem cell transplantation. Leuk Lymphoma 2011; 52: 1455–1462.

  11. 11

    Alvares CL, Davies FE, Horton C, Patel G, Powles R, Morgan GJ . The role of second autografts in the management of myeloma at first relapse. Haematologica 2006; 91: 141–142.

  12. 12

    Burzynski JA, Toro JJ, Patel RC, Lee S, Greene RE, Ochoa-Bayona JL et al. Toxicity of a second autologous peripheral blood stem cell transplant in patients with relapsed or recurrent multiple myeloma. Leuk Lymphoma 2009; 50: 1442–1447.

  13. 13

    Patriarca F, Einsele H, Spina F, Bruno B, Isola M, Nozzoli C et al. Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 2011; 8: 617–626.

  14. 14

    Shimoni A, Hardan I, Ayuk F, Schilling G, Atanackovic D, Zeller W et al. Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myeloma: long-term follow-up. Cancer 2010; 116: 3621–3630.

  15. 15

    Mehta J, Tricot G, Jagannath S, Ayers D, Singhal S, Siegel D et al. Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft? Bone Marrow Transplant 1998; 21: 887–892.

  16. 16

    Qazilbash MH, Saliba R, De Lima M, Hosing C, Couriel D, Aleman A et al. Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma. Cancer 2006; 106: 1084–1089.

  17. 17

    Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 2011; 117: 4691–4695.

  18. 18

    Shah N, Lonial S . Evidence-based mini-review: treatment options for patients with relapsed/refractory myeloma previously treated with novel agents and high-dose chemotherapy and autologous stem-cell transplantation. Hematol Am Soc Hematol Educ Program 2010; 2010: 310–313.

  19. 19

    Kumar S, Mahmood ST, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK et al. Impact of early relapse after auto-SCT for multiple myeloma. Bone Marrow Transplant 2008; 42: 413–420.

  20. 20

    Lenhoff S, Hjorth M, Turesson I, Westin J, Gimsing P, Wisloff F et al. Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation. Haematologica 2006; 91: 1228–1233.

  21. 21

    Mehta J, Singhal S . High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years. Bone Marrow Transplant 2007; 40: 1101–1114.

  22. 22

    Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol 2010; 28: 4630–4634.

  23. 23

    Barlogie B, Pineda-Roman M, van Rhee F, Haessler J, Anaissie E, Hollmig K et al. Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood 2008; 112: 3115–3121.

  24. 24

    Pineda-Roman M, Zangari M, Haessler J, Anaissie E, Tricot G, van Rhee F et al. Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Br J Haematol 2008; 140: 625–634.

  25. 25

    Jagannath S, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia 2007; 21: 151–157.

  26. 26

    Sagaster V, Ludwig H, Kaufmann H, Odelga V, Zojer N, Ackermann J et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia 2007; 21: 164–168.

Download references

Acknowledgements

This work was supported by Fund of Biomedical Research Institute, Chonbuk National University Hospital and also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (no. 20 110 029 703). This study was presented in part at the 2011 American Society of Hematology Annual Meeting in San Diego, CA, USA.

Author information

Correspondence to S-S Yoon or J-Y Kwak.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yhim, H., Kim, K., Kim, J. et al. Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT. Bone Marrow Transplant 48, 425–432 (2013). https://doi.org/10.1038/bmt.2012.164

Download citation

Keywords

  • auto-SCT
  • multiple myeloma
  • salvage therapy

Further reading