In newly diagnosed multiple myeloma (NDMM), renal impairment is a well-established risk factor leading to lower overall survival (OS) rates. Renal impairment is a modifiable risk factor and can be overcome with intensive therapy.
Using data from the CALM (Collaboration to collect Autologous transplant outcomes in Lymphoma and Myeloma) study database ( 42206644), Christoph Scheid, University of Cologne, Cologne, DE, and colleagues retrospectively analyzed the impact of renal function at diagnosis and at transplant, in patients with MM undergoing stem cell transplant. The results were presented during the 45th Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Frankfurt, Germany, on Wednesday 27 March 2019. The study was on behalf of the EBMT chronic malignancies working party (CMWP). 1
Study findings 1
- Patients receiving first autologous stem cell transplant (N = 1856)
- Information on renal function obtained at diagnosis and at transplant
- Patient characteristics at diagnosis are shown in
Table 1.
- Of note; a lower glomerular filtration rate (GFR) at diagnosis (<30) was more common in patients with ISS stage III disease and a lower proportion of these patients subsequently had a GFR ≥50 at transplant
- Most categories had comparable patient characteristics
Table 1:Patient characteristics by GFR at diagnosis
|
Factor |
GFR ≥50 |
GFR 30–50 |
GFR <30 |
P |
|---|---|---|---|---|
|
Age |
58 (22–75) |
60 (25–74) |
59 (27–76) |
0.045 |
|
Male vsfemale |
59% vs41% |
64% vs36% |
60% vs40% |
0.36 |
|
ISS stage (I vsII vsIII) |
45% vs38% vs12% |
10% vs37% vs47% |
6% vs16% vs71% |
<0.001 |
|
Karnofsky performance (<90% vs≥90%) |
29% vs71% |
29% vs71% |
40% vs60% |
0.007 |
|
≥ VGPR vsother |
45% vs55% |
52% vs48% |
50% vs50% |
0.006 |
|
CD34 +cells |
3.86 x 10 6/kg |
3.87 x 10 6/kg |
4.15 x 10 6/kg |
0.66 |
|
GFR ≥50 at transplant |
98% |
79% |
49% |
<0.001 |
|
Melphalan 200mg/m 2 vsother |
55% vs45% |
52% vs48% |
37% vs63% |
<0.001 |
| GFR, glomerular filtration rate; ISS, International Staging System; VGPR, very good partial response | ||||
Table 2:Renal function at diagnosis versustransplant by GFR rate
|
At diagnosis |
N |
At transplant |
N |
|---|---|---|---|
|
GFR ≥50 |
1408 |
GFR ≥50 |
1654 |
|
GFR 30–50 |
180 |
GFR 30–50 |
121 |
|
GFR <30 |
268 |
GFR <30 |
81 |
| GFR, glomerular filtration rate | |||
- GFR ≥50 at diagnosis:
- Maintained GFR rate: 1382
- Worsened to GFR 30–50: 22
- Worsened to GFR <30: 4
- GFR 30–50 at diagnosis:
- Maintained GFR rate: 31
- Improved GFR to ≥50: 142
- Worsened to GFR <30: 7
- GFR <30 at diagnosis:
- Maintained GFR rate: 70
- Improved GFR to 30–50: 68
- Improved GFR to ≥50: 130
- These results show that the current treatment options are effective at increasing renal function, especially in patients with a GFR < 30 at diagnosis.
Looking at the relationship between renal function at diagnosis and transplant and OS, progression-free survival (PFS), non-relapse mortality (NRM) and relapse incidence ( Table 3), it is possible to conclude that:
- Impaired renal function at diagnosis is a risk factor, leading to lower OS
- This is in line with findings of previous studies 2
- Renal function at transplant is not a risk factor for OS
- Professor Scheid stated that this was not found to be statistically significant, but noted that in the severely impaired group (GFR <30) there was an improved OS which warrants further investigation
- The overall negative effect of poor renal function on OS is not seen in PFS
- Having a poor renal function at transplant leads to a lower incidence of relapse
- There were no significant associations between renal status and NRM however patients whose renal status worsened after transplant had a higher rate of NRM
- Regarding relapse incidence:
- No effect of renal function at diagnosis
- However, renal function at transplant was highly significant
Patients with a poor renal function at diagnosis had better outcomes (OS and PFS) if they maintained their poor status at transplant, compared with those who improved their renal performance between diagnosis and transplant.
Table 3:Associations between OS, PFS, NRM, relapse incidence and renal function at diagnosis and transplant
|
Factor |
Renal function at diagnosis: Pvalue |
Renal function at transplant: Pvalue |
|---|---|---|
|
OS |
< 0.001 |
0.1 |
|
PFS |
0.8 |
0.003 |
|
NRM |
0.99 |
0.33 |
|
Relapse incidence |
0.74 |
0.0012 |
| NRM, ; PFS, progression free survival; OS, overall survival | ||
In order to explain these findings, a multivariate analysis (Cox model) was conducted ( Table 4). These results are clear, statistically, but difficult to interpret.
Table 4: Multivariate analysis of OS
| GFR, glomerular filtration rate; ISS, international Staging System; PR, partial response | ||
|
Factor |
Hazard ratio |
Pvalue |
|---|---|---|
|
GFR 30–50 at diagnosis |
1.12 |
0.22 |
|
GFR <30 at diagnosis |
2.2 |
< 0.0001 |
|
GFR 30–50 at transplant |
0.48 |
0.00034 |
|
GFR <30 at transplant |
0.25 |
< 0.0001 |
|
ISS stage II |
1.22 |
0.053 |
|
ISS stage III |
1.49 |
0.0028 |
|
Age |
1.01 |
0.10 |
|
Response < PR at transplant |
1.96 |
< 0.0001 |
|
Karnofsky 90–100% |
0.82 |
0.038 |
Conclusion
- This study confirmed previous findings that renal impairment at diagnosis is a negative prognostic factor but, surprisingly, that renal impairment at transplant did not significantly increase NRM.
- As PFS and OS were not negatively impacted by a failure to achieve a renal response between diagnosis and transplant, the authors recommended continuing transplanting these patients.
- Patients with persisting renal impairment (from diagnosis to transplant) had an improved OS and PFS. Hypotheses behind why this may be the case include:
- Renal impairment at transplant changes the bioavailability of melphalan
- There may be a patient selection bias (although the authors did not find a significant bias in patients enrolled in this study).
- Further studies are required to discover the reason for these findings.