EBMT 2019 | The role of renal impairment in patients with multiple myeloma undergoing autologous stem cell transplantation

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 findings¹

• 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 vs female	59% vs 41%	64% vs 36%	60% vs 40%	0.36
ISS stage (I vs II vs III)	45% vs 38% vs 12%	10% vs 37% vs 47%	6% vs 16% vs 71%	<0.001
Karnofsky performance (<90% vs ≥90%)	29% vs 71%	29% vs 71%	40% vs 60%	0.007
≥ VGPR vs other	45% vs 55%	52% vs 48%	50% vs 50%	0.006
CD34+ cells	3.86 x 106 /kg	3.87 x 106 /kg	4.15 x 106 /kg	0.66
GFR ≥50 at transplant	98%	79%	49%	<0.001
Melphalan 200mg/m2 vs other	55% vs 45%	52% vs 48%	37% vs 63%	<0.001
GFR, glomerular filtration rate; ISS, International Staging System; VGPR, very good partial response

Table 2: Renal function at diagnosis versus transplant 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 studies²
• 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: P value	Renal function at transplant: P value
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	P value
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.