Early Relapse After Autologous Stem Cell Transplantation in Multiple Myeloma is Still Prognostic in The Era of Novel Agents

Significant improvements in the prognosis of Multiple Myeloma(MM) have recently observed in the era of novel agents. Induction treatment, including new agents followed by conditioning regimen and upfront autologous stem cell transplantation(ASCT), has been accepted as the standard treatment approach for newly diagnosed eligible MM patients. Despite novel agents, upfront ASCT is still superior to conventional chemotherapy alone. Previous studies revealed that the duration between ASCT and relapse had predicted overall survival(OS), and meantime, it was widely used to determine the potential benefit from a second ASCT. However, the majority of the data collected reflects the treatment modalities before novel agents. In this study, we aimed to investigate the impact of post-transplantation early relapse(ER) on survival in the era of novel agents. The results of 155 MM patients that underwent ASCT at our center between January 2010 and May 2018 were analyzed retrospectively. The median follow-up duration was 20 months in the ER group, 27 months in the non-ER group, and 24 months in all patients. 33.3% of patients in the ER group and 71.4% of patients in the non-ER group were alive at the time of analysis. Median OS was 20.77±3.66 months in the ER group and 40.89±4.21 months in the non-ER group. We found a statistically significant relationship between the ER and the poor OS (p:<0.001). Our study reveals that in the era of novel agents, ER still related to poor survival. Therefore, comprehensive studies needed to develop new strategies for early relapsed patients.

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Re-invigorating rather than re-inventing the wheel: augmenting the impact of salvage autologous stem cell transplantation for multiple myeloma in the era of novel agents

Bone Marrow Transplantation ◽

10.1038/bmt.2015.175 ◽

2015 ◽

Vol 50 (10) ◽

pp. 1269-1270 ◽

Cited By ~ 2

Author(s):

G Cook

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Novel Agents ◽

The Impact

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Strategies to upgrade safety for at-home autologous stem cell transplantation in multiple myeloma patients.

10.21203/rs.3.rs-30978/v1 ◽

2020 ◽

Author(s):

Luis Gerardo Rodríguez-Lobato ◽

Alexandra Martínez-Roca ◽

Sandra Castaño-Díez ◽

Alicia Palomino-Mosquera ◽

Gonzalo Gutiérrez-García ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Hospital Readmissions ◽

Primary Prophylaxis ◽

Outpatient Setting ◽

The Impact ◽

At Home

Abstract Background. Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT.Methods. Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning + 1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT.Results. The incidence of NF among the groups was reduced (64%, 44%, and 24%; P < 0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI > 2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P < 0.001); and for hospital readmission: age ≥ 60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05).Conclusions. G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT.

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The Impact of Proliferating Polyclonal Plasma Cells on Outcome after Autologous Stem Cell Transplantation in Multiple Myeloma

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2019.12.485 ◽

2020 ◽

Vol 26 (3) ◽

pp. S239

Author(s):

Kevin C. Miller ◽

Michael Timm ◽

Dragan Jevremovic ◽

Morie Gertz ◽

Francis Buadi ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Plasma Cells ◽

The Impact

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

Blood Research ◽

10.5045/br.2013.48.3.198 ◽

2013 ◽

Vol 48 (3) ◽

pp. 198 ◽

Cited By ~ 2

Author(s):

Chang-Ki Min ◽

Sung-Eun Lee ◽

Seung-Ah Yahng ◽

Byung-Sik Cho ◽

Ki-Seong Eom ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Therapeutic Agents ◽

Before And After ◽

The Impact ◽

Novel Therapeutic

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Predictive impact of circulating microRNA‐193a‐5p on early relapse after autologous stem cell transplantation in patients with multiple myeloma

British Journal of Haematology ◽

10.1111/bjh.16413 ◽

2020 ◽

Vol 189 (3) ◽

pp. 518-523

Author(s):

Sung‐Soo Park ◽

Ji‐Young Lim ◽

Tae Woo Kim ◽

Yoon Ho Ko ◽

Wan‐Jin Jeon ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Circulating Microrna ◽

Early Relapse

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Thalidomide + Dexamethasone as Maintenance after Single Autologous Stem Cell Transplantation Improves Progression-Free Survival (PFS) in Advanced Multiple Myeloma. A Prospective Brazilian Randomized Trial

Blood ◽

10.1182/blood.v112.11.3703.3703 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3703-3703 ◽

Cited By ~ 4

Author(s):

Angelo Maiolino ◽

Vania T. Hungria ◽

G. Oliveira-Duarte ◽

LC Oliveira ◽

DR Mercante ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Disease Progression ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Chromosome 13 ◽

Beta 2 ◽

Beta 2 Microglobulin ◽

The Impact

Abstract Introduction: Autologous stem cell transplantation (ASCT) remains the mainstay of treatment of multiple myeloma (MM) in patients <65 years old. However, most patients relapse after ASCT suggesting that additional treatment is needed. The Brazilian Multiple Myeloma Group designed a study to evaluate the impact of thalidomide maintenance after ASCT. Methods: From October 2003 to July 2008, 212 untreated patients <70 years old were enrolled in a prospective randomized multicenter study. All patients signed an informed consent and the protocol was approved by the Ethical Committees of each center. The treatment consisted of 3 phases: induction with 3–5 cycles of VAD; high-dose cyclophosphamide (4g/m2) plus G-CSF for stem cell mobilization; (3) melphalan 200 mg/m2 and ASCT. On day +60 post ASCT patients were randomized to receive dexamethasone (40 mg/d × 4 days every 28 days) with (arm A) or without (arm B) thalidomide (200 mg daily) for 12 months or until disease progression. Results: The median age was 55 years (27–70), 52% were male, the median serum beta-2 microglobulin was 3.66 mg/dl, 33% were ISS stage 3, 36% were ISS stage 2 and 24% had deletion of chromosome 13. In July of 2008, 93 patients (44%) were randomized: 54 in arm A and 39 in arm B. Reasons for non-randomization were: treatment related deaths during phases 1–3 (n= 39), disease progression (n= 22), ineligible or refused ASCT (n= 7), SMD after ASCT (n= 1), protocol violation (n= 3), abandoned (n= 19), and still in phases 1–3 (n= 28). Clinical characteristics of each group were similar. The median follow-up from diagnosis was 15 months. PFS in arms A and B were 42% (95% confidence interval [CI] 22–62) and 25% (95% CI 5–45), p= 0.07. A multivariate analysis that included baseline serum beta-2-microglobulin and deletion of chromosome 13 showed that maintenance with thalidomide was significantly associated with better PFS (hazard ratio 2.43, 95% CI 1.10–5.35, p=0.03). Overall survival was 65% in arm A (95% CI 35–95) and 74% in arm B (95% CI 44–100), p= NS. Conclusions: A high proportion of MM in Brazil has advanced disease at diagnosis, and this explains the high number of patients who did not reach the maintenance phase. This study shows that the addition of thalidomide to dexamethasone improves PFS after a single ASCT.

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Second Autologous Stem Cell Transplantation Is Effective Salvage Therapy for Relapsed Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.1229.1229 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1229-1229 ◽

Cited By ~ 1

Author(s):

Aristeidis Chaidos ◽

Chrissy Giles ◽

Holger W Auner ◽

Marco Bua ◽

Jiri Pavlu ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Salvage Treatment ◽

Treatment Modalities ◽

Significant Prognostic Factor ◽

Group 4 ◽

Group 3

Abstract Abstract 1229 Poster Board I-251 Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is standard treatment for the non-elderly multiple myeloma (MM) patients. Relapses invariably occur and therefore reinduction therapy followed by ASCT is often considered. We retrospectively analysed the results of second ASCT after relapse and re-induction and assessed the effect of bortezomib therapy prior to second ASCT. We included 177 MM patients who relapsed after the initial melphalan 140-200mg/m2 ASCT and treated in a single institution from July 1994 to April 2009. Patients who received melphalan/TBI conditioning, planned upfront tandem transplants, allogeneic SCT, palliation only or who suffered early death or death in remission were excluded from our analysis. The patients were divided into 4 groups based on the type of salvage treatment. Group 1 included 96 patients with median age 59.6 years (range 31.16 – 73.5) at the time of progression who were salvaged with treatment modalities other than a second ASCT or bortezomib. Group 2 received bortezomib based salvage but not a second ASCT and included 31 patients aged 61.7 years (49.3 – 72.9), group 3 included 28 patients aged 58.6 years (31.1 – 70.6) who were treated with a second ASCT and no bortezomib, and finally group 4 included 22 patients aged 59.1 years (32.6 – 70.6) who were treated with bortezomib and second ASCT. For the transplanted patients, the conditioning consisted of melphalan 140-200mg/m2. Bortezomib was given at standard doses (1.3mg/m2 at days 1,4,8, and 11) plus dexamethasone 20mg same and next day of bortezomib injection for 3 to 4 21-day cycles. Survival was estimated from the time of progression after the initial transplant. Univariate analysis showed longer survival for the transplanted patients (median 41.2 and 60.9 months for groups 3 and 4, 15.2 and 29.8 months for groups 1 and 2 respectively, Log Rank p=0.003). In multivariate Cox analysis the type of salvage treatment retained significance (p=0.013, OR 2.75, 95%CI 1.23 – 6.16). When patients treated with a second ASCT (groups 3 and 4) were analysed separately, the difference in survival between groups did not reach significance (p=0.32). Multivariate analysis showed longer survival if complete remission (CR) or near CR (nCR) had been achieved with the first ASCT (p=0.05, OR 6.4 95%CI 1.7 – 23.19) and if disease progression had occurred at least 12 months after the initial ASCT (p<0.001, OR 13 95%CI 3.74 – 45.15). The latter was also the only parameter to predict longer progression free survival (PFS) after the second ASCT (p=0.004, OR 5.2 95%CI 1.7 – 15.8). On the contrary, PFS was 19.1 months for group 3 and 10.1 months for group 4 (p=0.52). Similarly, age >65 years, reduced melphalan dose (<200mg/m2) and the immunoglobulin subtype of MM did not appear to affect the PFS or survival after a second ASCT. In conclusion, a second ASCT is an effective approach compared to other salvage treatments. A progression-free period of >12 months following the initial ASCT is the most significant prognostic factor of PFS and survival after the second ASCT. Bortezomib based induction is suggested to improve CR and nCR rates after the first ASCT, however its use prior to second ASCT does not appear to produce longer PFS or survival. Disclosures No relevant conflicts of interest to declare.

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