Prognosis of concurrent renal impairment at diagnosis of multiple myeloma: a systematic review

Figures & data

Table 1. Search strategy.

S. No.	Search terms	PubMed	Web of science	Embase	Cochrane	CNKI	Wanfang	VIP
#1	Multiple Myeloma	59,981	104,990	109,286	6,005	14,451	39,498	5,003
#2	Plasma-Cell Myeloma	60,821	20,848	100,410	900	59	162	83,402
#3	Myelomas	73,491	121,203	1,678	150	12	860	5,582
#4	Myeloma, Plasma	14,688	24,638	27,754	1,249	226	7,879	147
#5	(#1) OR (#2) OR (#3) OR (#4)	73,491	121,203	112,456	6,065	34	35,774	88,392
#6	Renal Insufficiency	214,259	91,018	207	12	13,435	57	1,311
#7	Kidney Insufficiency	215,873	74,001	518,753	5,370	12,347	5,940	7
#8	Kidney Failure	260,315	264,986	602,617	22,270	58,554	41,823	44
#9	Renal Failure	290,995	291,929	599,996	23,092	49,651	88,734	8,829
#10	(#6) OR (#7) OR (#8) OR (#9)	308,632	382,987	644,800	32,396	70,376	105,618	10,048
#11	(#5) AND (#10)	2,614	4,314	7,934	303	0	803	227
#12	Progression-Free Survival	84,824	83,472	171,657	30,219	2,819	33,050	305,579
#13	Event-Free Survival	86,300	20,200	34,427	4884	320	7,457	55,645
#14	Survival, Progression-Free	84,826	83,472	171,655	30,219	179	32,223	125
#15	(#12) OR (#13) OR (#14)	100,075	102,399	203,477	34,434	3,115	40,281	337,658
#16	((#5) AND (#10)) AND (#15)	114	295	1006	109	0	28	1

Figure 1. PRISMA study flow chart.

Table 2. Characteristics and quality scores of included studies.

Studies	Country	Peroid	Type of research	Number	Definition of renal insufficiency	Case(male/female), age(min − max)	Control(male/female), age(min − max)	Treatment in the case group	Outcome	NOS Score
Sirohi et.al 2001 [17]	United Kingdom	1985 − 1998	Cohort − study	251	Cr > 140 μmol/L (1.6 mg/dL)	59(43/16) 52(30 − 74)	192(115/77) 53(31 − 73)	Total sequential therapy; Patients with symptoms of hyperviscosity should be considered for plasmapheresis.	Median OS: 2.5 y (95%CI: 1.2 − 4.2y) vs 4.6 y (95%CI: 3.6 − 5.8y) (p = 0.0025). Median EFS: 1.2 y (95%CI: 0.7 − 2.3 y) vs 2.1 y (95%CI: 1.7 − 2.5y) (p = 0.07).	7
Dimopoulos et.al 2010 [19]	Greece	2007 − 2009	Cohort − study	50	Ccr < 50 mL/min	12(4/8) 74.5(50 − 87)	38(22/16) 68(43 − 82)	Ccr > 50 mL⁄min: Lenalidomide 25 mg orally was given. For patients with low Ccr values, adjustments were made on day 1 after dialysis: Ccr ≥ 30 mL⁄min and <50 mL⁄min, Lenalidomide 10 mg⁄day; Lenalidomide 15 mg once every other day for patients with Ccr < 30 mL⁄min and not yet on dialysis; In dialysis patients, lenalidomide was 15 mg 3 times a week after dialysis.	PFS: 9 m (3 − 14 m) vs 8 m (4 − 11 m) (p = 0.77); OS: 14 m (10 − 17 m) vs 16 m (10 − 21 m) (p = 0.91)	6
Scheid et.al 2014 [20]	Germany	unknown	Cohort − study	827	Cr > 2 mg/dL	81(NA) 57(25 − 65)	746(NA) 57(38 − 65)	Patients were randomized 1:1 to Vincristine, adriamycin, and dexamethasone induction therapy, high-dose equifarin and ASCT intensive therapy, and thalidomide 50 mg daily maintenance therapy; Or bortezomib, doxorubicin, and dexamethasone were induced with high-dose equifarin /ASCT followed by maintenance therapy with bortezomib 1.3 mg/m^2 i.v. Twice a week for two years. Patients with Ccr < 40 mL/min were given a high dose of 200 mg/m^2 or 100 mg/m^2 equine.	Follow − up for 41 months, 3-year PFS rate: 30% vs 46%, p < 0.001); 5 − year PFS rate: 20% vs 26%, p < 0.001); 3 − year OS rate: 51% vs 78%, p < 0.001), 5 − year OS rate: 33% vs 61%, p < 0.001).	7
Raab et.al 2006 [18]	Germany	1996 − 2004	Case − control	34	Receive dialysis treatment	17(9/8) 57(39 − 65)	17(12/5) 59(43 − 64)	The preconditioning regimen of the control group was 200 mg/m^2 and that of the dialysis group was 100 mg/m^2	Median follow − up time: 35 m, EFS (23.4 m vs 18.3 m. p = 0.71); OS (35.6 m vs 52.3 m, p = 0.44)	6
Zhu et.al 2015 [21]	China	2010 − 2012	Case − control	897	Cr ≥ 177μmol/L	177(NA) 59 ± 10	720(NA) 59 ± 11	None	Median follow − up time: 24 m(2 − 114m); PFS: 28 m (95%CI 22.4 − 33.0 m) vs 29 m (95%CI 25.6 − 32.4 m), p = 0.46; OS: 44.0 m (95%CI 37.7 − 50.3 m) vs 59.2 m (95%CI 49.7 − 68.7 m) (p = 0.03)	8
Sweiss et.al 2016 [22]	USA	2001 − 2012	Case − control	149	Ccr < 60 mL/min	46(15/31) 61(38 − 77)	103(52/51) 58(34 − 74)	All patients received melphalan 200 mg/m^2 intravenously for 2 days, followed by ASCT 24 h later.	OS: 35 m (2 − 132 m) vs 47 m (1 − 45m) (P = NS). TFS: 37 m vs 17 m (p = 0.0025).	7

Abbreviations: NA: Not available; NS: No significance; OS: Overall survival; PFS: Progression − free survival; EFS: Event − free survival; RFS: Recurrence − free survival; TFS: Treatment free survival; m: months; y: years; i.v: Intravenous injection.

Sirohi B, Powles R, Mehta J, et al. The implication of compromised renal function at presentation in myeloma: similar outcome in patients who receive high-dose therapy: a single-center study of 251 previously untreated patients. Med Oncol. 2001;18(1):39–50. doi:10.1385/mo:18:1:39.

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Dimopoulos MA, Christoulas D, Roussou M, et al. Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment. Eur J Haematol. 2010;85(1):1–5. doi:10.1111/j.1600-0609.2010.01432.x.

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Scheid C, Sonneveld P, Schmidt-Wolf IG, et al. Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/GMMG-HD4 trial. Haematologica. 2014;99(1):148–154. doi:10.3324/haematol.2013.087585.

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Raab MS, Breitkreutz I, Hundemer M, et al. The outcome of autologous stem cell transplantation in patients with plasma cell disorders and dialysis-dependent renal failure. Haematologica. 2006;91(11):1555–1558.

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Zhu W, Lu J, Lu J, et al. [Clinical analysis of newly diagnosed multiple myeloma patients with renal dysfunction]. Zhonghua Yi Xue Za Zhi. 2015;95(10):741–744.

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Sweiss K, Patel S, Culos K, et al. Melphalan 200 mg/m 2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival. Bone Marrow Transplant. 2016;51(10):1337–1341. doi:10.1038/bmt.2016.136.

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Data availability statement

The dataset from which information was collected may be shared by contacting the corresponding author.