Serum beta2-Microglobulin before Transplantation Is an Independent Predictor of Outcome in Patients with Multiple Myeloma Treated Using Autologous HCT; a Single Centre Multivariate Analysis in a Series of 81 Patients.
Authors: Stella-Holowiecka Beata M. , Czerw Tomasz , Holowiecka-Goral Aleksandra M. , Giebel Sebastian , Wojnar Jerzy , Holowiecki Jerzy 
Published: April 2020

High-dose therapy combined with autologous stem cell transplantation-AHCT has been found effective both for up-front therapy and for management of chemotherapy sensitive relapses in multiple myeloma (MM). The results of five randomized trials are controversial; most have confirmed the advantage of AHCT in terms of CR and DFS but a significantly better OS was reported in only one study. It is unclear whether the entirety of MM patients benefit from the higher efficacy of AHCT versus standard chemotherapy or the better results reflect rather a high efficacy in certain subset of patients. It is of crucial importance therefore to define predictive factors characterizing patients who may benefit from therapy including AHCT.

The main objective was to select pre-transplant factors predictive for the efficacy of autoHCT in patient with MM treated using defined standard operating procedures in single center from January 1993 to April 2005.

Material and methods: 81 MM patients, undergoing first autoHSCT in single transplant centre: median age at autoHSCT 51 y (31–70), F/M 38/43, median time from diagnosis to autoHSCT 12 months (6–68), MM subtype: IgG n=51, IgA −13, non-secretory-7, not-defined −10; source of stem cells: PB −79, BM -2, conditioning: melphalan 200 mg /m2 (n=76), other (n=5), disease status: CR −30, PR-51.

Factors submitted for multivariate analysis: serum beta2-microglobulin (b2-mgl), lactate dehydrogenase (LDH), monoclonal protein level (MoP), bone marrow plasma cell percentage (BM-pc), hemoglobin level (Hb), age ≤60 vs. &gt; 60y and the number of transplanted CD34 positive cells ≤ median value equaling 7,18 x 106/kg vs. &gt; this number. Factors were measured within the median time of 7 d before initiation of conditioning regimen.

Results: The transplant related mortality at day 100 was 3,7%; the relapse incidence - RI at 9,2 y equaled 74% for patients with elevated b2m and 32% for those with b2m within normal range, p=0.02. Other factors included in multivariate analysis were: BM - pc ≥ 5% vs. &lt; 5% (100% vs. 55%, p=0.07) and MoP elevated vs. within normal limits (77% vs. 59%, p=0.1).

The progression free survival - PFS was decreased in patients with elevated b2-mgl (29% vs. 68%, p=0.02), in these with BM - pc ≥5% (0% vs. 45%, p=0.03) and with elevated MoP (22% vs. 40%, p=0.1). Coincident observations in our MM patients suggest that elevated b2-mgl is more frequent in patients displaying 13q−.

In multivariate analysis b2-mgl remained the only factor associated with increased risk of relapse (hazard ratio=3.29, p=0.03) and reduced probability of PFS (hazard ratio=3.29, p=0.03)

Conclusion: Serum beta2-microglobulin before first autoHCT is a reliable independent predictor for RI and PFS duration in MM patients, ipso facto it is helpful in appraisal of patients who may benefit from myeloablative therapy followed by autoHCT.