scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

Combining bortezomib to high dose melphalan as conditioning regimen results in the improvement of the response rate in newly diagnosed young multiple myeloma patients

2020 ◽  
Vol 61 (5) ◽  
pp. 1238-1241
Author(s):  
Benedetta Dalla Palma ◽  
Fabrizio Accardi ◽  
Lucia Prezioso ◽  
Laura Notarfranchi ◽  
Nicola Giuliani
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Conditioning Regimen ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Melphalan

scholarly journals Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-HD4 Trial

2012 ◽  
Vol 30 (24) ◽  
pp. 2946-2955 ◽  
Author(s):  
Pieter Sonneveld ◽  
Ingo G.H. Schmidt-Wolf ◽  
Bronno van der Holt ◽  
Laila el Jarari ◽  
Uta Bertsch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Staging System ◽  
Complete Response ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Primary Analysis ◽  
Risk Patients ◽  
High Dose Melphalan

Purpose We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). Patients and Methods In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m2 (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. Results Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003). Conclusion Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.

Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib

2017 ◽  
Vol 24 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Eda Aypar ◽  
Fikret Vehbi İzzettin ◽  
Şahika Zeynep Akı ◽  
Mesut Sancar ◽  
Zeynep Arzu Yeğin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Standard Of Care ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Duration Of Hospitalization ◽  
High Dose Melphalan

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.

Sequential High-Dose Dexamethasone and Response Adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Open-Labelled, Multicenter Phase 2 Study (KMM-94 Study)-Interim Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2044-2044
Author(s):  
Jin Seok Kim ◽  
Cheolwon Suh ◽  
June-Won Cheong ◽  
Kihyun Kim ◽  
Yang Soo Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Younger Patients ◽  
High Dose Dexamethasone

Abstract Abstract 2044 Background: Induction treatment followed by autologous stem cell transplantation (ASCT) is the standard therapy for the newly diagnosed younger patients with multiple myeloma (MM). Although new drugs such as lenalidomide or bortezomib have been shown the promising results as induction treatment, many different type of induction treatment regimens still have been used. We evaluate the efficacy and safety of the short course of high dose dexamethasone (HD dexa) and the response adapted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy in the newly diagnosed younger patients with MM. Methods: 107 newly diagnosed patients with MM from 21 institutions received 2nd cycles of HD dexa followed by PAD or VAD chemotherapy according to the response to the initial high dose dexamethasone. The primary endpoint was complete response (CR) + near CR rate after ASCT. Among 107 patents enrolled this study from November 2009, 25 patients (23%) have been dropped out. This trial will be continued until total 210 patients will be enrolled. The trial is registered on National Cancer Institute website, number NCT01255514. Results: One hundred seven patients (58 male, 49 female) were enrolled (median age; 56). 26 (24%) light chain disease were included. 31 (29%) patients were D-S stage II and 67 (63%) were stage III. According to the ISS, 23 (22%) patients had stage I, 51 (48%) had stage II and 33 (31%) had stage III. 26 (24%) patients had abnormal cytogenetics. There were 31% del13, 7% del17, 19% t(4;14), 15% t(14;16) and 28% t(11;14) in FISH analysis. Among the 82 evaluable patients, CR + PR rate was 48% (39/82) after 2nd cycles of HD dexa therapy. 39 patients (48%) received subsequent VAD chemotherapy and 43 patients (52%) received PAD chemotherapy. Among the 64 patients finished VAD or PAD chemotherapy, CR + PR rate was 83% (79%, 26/33 in VAD group vs. 87%, 27/31 in PAD group). 56 patients were finished ASCT until now. CR + near CR rate after ASCT were 61% (58% in VAD group vs 63% in PAD group). Mortality rate of this trial was 13% (11/82). The cause of death was disease progression (n=3), bleeding (n=1) and infections (n=7). Among 82 patients in whom VAD or PAD chemotherapy was actually performed, 1 year overall survival (OS) rate was 84.7%. 1 year survival rate was 93.8% versus 77.2% (P=0.049) with VAD versus PAD (median follow-up; 9.1 months). Conclusion: Risk adapted approach using initial steroid response showed good response results after ASCT compared with previous trial (CR + near CR rate of IFM 2005-01trial-Bortezomib+dexa induction & ASCT was 35%, J Clin Oncol. 2010;28:4621–9) The MM patients who had poor response to HD dexa also showed similar good response rate after ASCT compared with the patients who had good response to HD dexa treatment in this trial. PAD re-induction therapy after failure of initial steroid induction treatment might overcome the inferior results in the high risk MM patients. Therefore, initial steroid response adapted strategy might be the more cost-effective approach in the newly diagnosed ASCT eligible MM patients. Disclosures: No relevant conflicts of interest to declare.

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