Prognostic Role of Beta-2 Microglobulin in Patients with Light Chain Amyloidosis Treated with Autologous Stem Cell Transplantation

e20506 Background: Autologous stem cell transplantation (ASCT) prolongs survival in patients with light chain (AL) amyloidosis. Mayo 2012 stage and increased plasma cell percentage (%PC) are known predictors for survival. Increased beta-2 microglobulin (B2M) predicts survival in patients with multiple myeloma. However, its prognostic effect in patients with AL amyloidosis undergoing ASCT is not known. Methods: We retrospectively reviewed patients who had a diagnosis of AL amyloidosis and were treated with ASCT between July-1996 and September-2017. Patients with creatinine > 1.2 mg/dL were excluded, as that affects B2M levels. The receiver operator curve was used to determine the best cutoff for B2M in predicting survival and was 2.5 mcg/mL. Baseline characteristics were compared between patients with B2M > 2.5 and ≤2.5. Progression-free survival (PFS) was defined as time from ASCT to relapse or death, whichever occurred first. Overall survival (OS) was calculated from ASCT to death of any cause. Univariate and multivariate analysis were done for OS. Results: Five-hundred patients were identified and 222 (44%) had a B2M > 2.5. These patients were more likely to be > 65 years old (32% vs. 17%, P = 0.0001), have Mayo 2012 stage III/IV (33% vs. 8%, P < 0.0001), have ≥3 organs involved (25% vs. 14%, P = 0.001), and have ≥10% PCs (56% vs. 40%, P = 0.0002) compared to patients with B2M ≤2.5. The median PFS and OS were shorter in patients with B2M > 2.5 (median PFS: 64 vs. 80 months, P = 0.03); (median OS: 104.9 vs. 175.5 months, P < 0.0001). On univariate analysis, predictors for OS included age > 65 (HR: 1.6, P = 0.001), Mayo 2012 stage III/IV (HR: 3.3, P < 0.0001), ≥3 organs involved (HR: 1.3, P = 0.06), ≥10% PC (HR: 1.5, P = 0.004), melphalan conditioning 200mg/m2 (HR: 0.28, P < 0.0001), and B2M > 2.5 (HR: 1.8, P < 0.0001). In a multivariate analysis, only Mayo 2012 stage III/IV (HR: 1.8, P = 0.006), melphalan conditioning 200mg/m2 (HR: 0.35, P < 0.0001), and B2M > 2.5 (HR: 1.7, P = 0.01) remained independent predictive of OS. Conclusions: Beta-2 microglobulin > 2.5 is an independent predictor for OS in AL amyloidosis patients undergoing ASCT and should be routinely measured.

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Evolving Role of Autologous Stem Cell Transplantation for Light Chain Amyloidosis in the Modern Era

ONCOLOGY ◽

10.46883/onc.2021.3508.0474 ◽

2021 ◽

pp. 474-475

Author(s):

Muhamed Baljevic

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Light Chain ◽

Light Chain Amyloidosis ◽

Modern Era

Muhamed Baljevic, MD, considers the role of autologous stem cell transplantation for light chain amyloidosis in a peer perspective accompanying an article by Iuliana Vaxman, MD, and Angela Dispenzieri, MD.

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A 24‐year experience of autologous stem cell transplantation for light chain amyloidosis patients in the United Kingdom

British Journal of Haematology ◽

10.1111/bjh.16143 ◽

2019 ◽

Vol 187 (5) ◽

pp. 642-652 ◽

Cited By ~ 6

Author(s):

Faye A. Sharpley ◽

Aviva Petrie ◽

Shameem Mahmood ◽

Sajitha Sachchithanantham ◽

Helen J. Lachmann ◽

...

Keyword(s):

United Kingdom ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Light Chain ◽

Light Chain Amyloidosis ◽

The United Kingdom

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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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