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As part of this month’s editorial theme, the Multiple Myeloma Hub is focusing on the clinical outlook of high-risk multiple myeloma (MM), and how patient prognosis can be improved in this setting. Despite significant advances in treatment options for patients with MM in recent decades, certain cytogenic aberrations are still associated with inferior outcomes in MM.
Currently employed standard-of-care regimens for patients with newly diagnosed MM (NDMM) have improved survival outcomes, but patients harboring del(17p) and/or t(4;14) genetic alterations have been identified as particularly high risk, and benefit least from emerging treatments. Among efforts to improve patient outlook, tandem transplantation has been employed in certain settings. However, the benefit of a tandem transplant remains ill-defined and, until now, no studies have reported alternative transplant approaches in distinct cytogenetic groups in the real-world setting.
In an endeavor to provide answers, Nico Gagelmann et al.1 evaluated patients with high-risk NDMM with del(17p) and/or t(4;14) undergoing frontline treatment with single autologous (auto), tandem autologous (auto-auto), or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation (SCT). Data were obtained from the European Society for Blood and Marrow Transplantation (EBMT) registry, and the results were published in Bone Marrow Transplant—below is a summary.
Table 1. Baseline patient characteristics1
Auto, single autologous; auto-allo, tandem autologous/reduced-intensity allogeneic; auto-auto, tandem autologous; CA, cytogenetic aberration |
|
Characteristic |
Total patient population (N = 623) |
Median age, years (range) |
59 (25.6–76.7) |
Male, % |
55.5 |
Transplant, % |
|
Auto (n = 446) |
71.6 |
Auto-auto (n = 105) |
16.9 |
Auto-allo (n = 72) |
11.6 |
ISS, % |
|
I |
20.9 |
II |
57.5 |
III |
21.7 |
Cytogenetics, % |
|
del(17p) |
44.8 |
t(4;14) |
46.5 |
Both |
8.7 |
Number of high-risk CAs, % |
|
1 |
77.0 |
≥ 2 |
23.0 |
Bortezomib-based induction regimen, % |
69.2 |
Months from diagnosis to first transplant, median (range) |
5.6 (2.2–11.7) |
Table 2. Patient outcomes to frontline transplant across the study cohort1
NRM, non-relapse mortality rate; OS, overall survival; PFS, progression-free survival |
|
Outcome, % (range) unless otherwise stated |
Entire cohort (N = 623) |
Median follow-up, months (range) |
58 (53–63) |
5-year OS |
49 (44–54) |
5-year PFS |
20 (16–24) |
5-year relapse rate |
77 (73–81) |
NRM |
3 (2–5) |
Table 3. Patient outcomes to frontline transplant with respect to transplant approach and cytogenetic abnormalities
NRM, non-relapse mortality rate; OS, overall survival; PFS, progression-free survival |
||||
Transplant approach |
||||
Outcome, % (range) unless otherwise stated |
Single auto (N = 446) |
Auto-auto (N = 105) |
Auto-allo (N = 72) |
p |
Median follow-up, months |
56 |
52 |
63 |
— |
5-year OS |
51 (45–58) |
60 (49–72) |
67 (53–80) |
0.187 |
5-year PFS |
17 (12–22) |
33 (22–43) |
34 (21–38) |
0.048 |
5-year relapse rate |
82 (77–87) |
63 (52–74) |
56 (42–70) |
0.001 |
NRM, % |
1 |
4 |
10 |
— |
Cytogenetics |
||||
Outcome, % (range) |
t(4;14) |
del(17p) |
t(4;14) + del(17p) |
p |
5-year OS |
53 (46–60) |
44 (37–51) |
52 (37–67) |
0.463 |
5-year PFS |
20 (15–26) |
20 (14–26) |
16 (5–28) |
0.179 |
5-year relapse rate |
76 (70–82) |
77 (71–83) |
78 (66–91) |
0.311 |
NRM |
3 (1–6) |
3 (1–5) |
6 (0–12) |
0.531 |
When adjusted for patient baseline characteristics, the outcomes of the different transplant strategies depended on the type of cytogenetic aberration present:
PFS rates following tandem auto-allo were superior to single auto (HR, 0.54; 95% CI, 0.23–0.87; p 0.018), but OS was comparable
Nico Gagelmann and colleagues established that frontline treatment with tandem autologous transplant was associated with superior PFS and relapse rates compared with single auto-SCT in patients with NDMM and t(4;14). In addition to the positive results from the EMN02/HO95 trial in patients with del(17p) and the STAMINA study, these data support the benefit of a tandem auto-SCT in patients with high-risk cytogenetics.
On the other hand, the higher NRM rates, together with the limited number of patients, impedes to make a clear recommendation on the use of tandem auto-allo based only on this real-world study.
At the 45th Annual Meeting of the EBMT in 2019, Nico Gagelmann summarized for the Multiple Myeloma Hub the reported outcomes of this study:
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