Salvage auto-HCT outcomes with remobilized stem cells in multiple myeloma

Mobilized peripheral blood stem cells on the bone marrow are important for a successful autologous hematopoietic cell transplantation (auto-HCT). As such, collecting sufficient numbers of CD34⁺ cells is critical for a robust hematopoietic recovery and sustained engraftment.¹ When patients with multiple myeloma (MM) relapse after first-line auto-HCT, some may benefit from a second salvage transplant; however, this may be a challenge in older and heavily pretreated patients, and remobilization of stem cells is required.²

Joanna Drozd-Sokolowska and colleagues conducted a retrospective study (on behalf of the European Society for Blood and Marrow Transplantation [EBMT] Chronic Malignancies Working Party) to investigate the short- and long-term safety and efficacy of salvage auto-HCT performed with cells remobilized after a previous auto-HCT, to increase knowledge of this approach. The study results were presented at the 47th Annual Meeting of the EBMT,² and here, we are happy to summarize the key points.

Study design²

The study included patients with relapsed MM who underwent salvage auto-HCT in 2000–2018, which was performed with cells remobilized following the previous auto-HCT. Time from the previous transplant to remobilization was longer than 6 months.

The primary endpoint was non-relapse mortality. Secondary endpoints included timing of recovery, overall survival (OS), progression-free survival (PFS), relapse incidence, the cumulative incidence of therapy-related myelodysplastic syndromes/acute myeloid leukemia, and the cumulative incidence of other secondary primary malignancies (SPM).

Patients

The number of patients included in the study was 305, and two-thirds of patients were male. Table 1 summarizes patient characteristics.

Table 1. Patient characteristics*

auto-HCT, autologous hematopoietic cell transplantation; IQR, interquartile range. *Data from Drozd-Sokolowska et al.2
Characteristic	N = 305
Median age at salvage auto-HCT, years (IQR)	59 (53–63)
Median time between the last non-salvage auto-HCT and the first progression, months (range)	30.6 (1.2–147.3)
Median interval between the previous auto-HCT and salvage remobilization, months (range)	43.9 (7.1–152)
Number of therapy lines between previous auto-HCT and salvage auto-HCT, n (%)
1               2               ≥3	132 (49) 86 (32) 49 (19)
Patients who received plerixafor in any mobilization regimen, n (%)	52 (17)
Median total collected CD34+ cells, × 106/kg	3.39 (0.24–16)

Patients commenced salvage auto-HCT following a conditioning regimen with melphalan; only one patient did not receive melphalan. Stem cell source was peripheral blood alone in most patients (97%); bone marrow was used in 1% (n = 4), and peripheral blood + bone marrow was used in 2% (n = 6). The median total infused of CD34+ cells was 2.92 × 10⁶/kg (range, 1.07–24.5).

Results²

Median follow-up was 31 months (95% CI, 25.9–36.4). Median OS and PFS were 51 months (95% CI, 42–61) and 17 months (95% CI, 15–21), respectively. Outcomes with salvage auto-HCT are presented in Table 2.

Table 2. Outcomes*

c.i., cumulative incidence; CI, confidence interval; NRM, non-relapse mortality; OS, overall survival; PFS, progression-free survival; RI, relapse incidence; SPM, secondary primary malignancy; t-AML; therapy-related acute myeloid leukemia; t-MDS, therapy-related myelodysplastic syndromes. *Data from Drozd-Sokolowska et al.2
Outcome, % (95% CI)	2-year	4-year
NRM	5 (2–7)	9 (5–12)
RI	56 (50–62)	81 (76–86)
OS	76 (71–81)	52 (45–58)
PFS	39 (33–45)	15 (11–20)
t-MDS/t-AML c.i.	1 (0–3)	3 (1–5)
Other SPM c.i.	1 (0–2)	3 (1–5)

Hematopoietic recovery was similar between first and salvage auto-HCT, except for platelet counts >50 × 10⁹/L (Table 3).

Table 3. Hematopoietic recovery*

ANC, absolute neutrophil count; auto-HCT, autologous hematopoietic cell transplantation; PLT, platelet count. *Adapted from Drozd-Sokolowska et al.2
Parameter	Median time to recovery, days (95% CI)
	First auto-HCT	Salvage auto-HCT	p value
ANC >0.5 × 109/L	12 (11–14)	12 (11–14)	0.30
PLT >20 × 109/L	12 (11–15)	13 (11–16)	0.08
PLT >50 × 109/L	16 (13–21)	20 (14–34)	<0.001

The univariate analysis demonstrated OS and PFS benefit when the time interval between the last non-salvage auto-HCT and the first progression was >30 months. Interestingly, patients who underwent salvage auto-HCT before 2005 appeared to have inferior outcomes, suggesting that the year of salvage auto-HCT impacted survival. These two variables also showed statistical significance in the multivariate analysis.

Conclusion

This study demonstrated that salvage auto-HCT with remobilized stem cells following a previous auto-HCT led to satisfactory rates of non-relapse mortality and an expected cumulative incidence of secondary primary malignancies in patients with MM. Disease progression was considered the main cause of treatment failure, with possible predictors being the time between previous non-salvage auto-HCT and the first relapse (>30 months) and the year of salvage auto-HCT.