A Single Center Study Investigating Clinical Outcomes of Testing for Multiple Myeloma and Immune Deficiency at Low Globulin Levels

Figures & data

Figure 1 Flow chart of analysis of patient samples.

Table 1 Diagnosis of Patients with Globulin Levels ≤ 16 g/L

	n	IgG Range at Globulin Levels ≤ 16 g/L (RR 7–16 g/L)	Age Years (Range)	Female %	Reflex Tested During Jan 2019-Dec 2019%	Numbers Detected by Reflex Testing Compared to Patients with Hematology Malignancies	% Treated with Prophylactic Antibiotics or Immunoglobulin Replacement	% Referred for Specialist Immunology and Hematology	Numbers Referred for Specialist Immunologist/Hematology Opinion Compared with Patients with Hematology Malignancies
Hematology	116	<3–7 g/L; median: 3.95	72 (34–86)	47	36		12.9%	100%
Immunosuppressant treatment	35	<3–7.3; median: 4.9	72 (36–88)	61	89	p <0.001	0%	5.7%	ρ <0.001
Antiepileptic treatment	11	<3–5.0; median: 4.5	60 (33–83)	70	80	ρ <0.001	0%	0%	p <0.001
Combination treatment with antiepileptics and immunosuppressants	4	<3–5.5; median: 5	72 (57–82)	50	75	*
Non-hematology malignancy (breast and renal malignancy)	2	<3–3.1; median: 3.1	82, 87	50	50	*
Light chain myeloma	20	<3–6.7; median: 4.65	70 (48–87)	60	15	ρ <0.001**	5%	100%
CVID	4	<3–-4; median: 3.7	52 (38–61)	75	100	*
Patients with non-related co-morbidities	57	<3–8.5; median: 5.5	67 (33–97)	40	82	ρ <0.001	0%	19.3%	p <0.001

Notes: *Patient numbers <10; **Patients under the care of hematology specialists.

Figure 2 IgG levels at different globulin concentrations. The lower reference range of IgG = 7 g/L is indicated by the horizontal line in the figure. IgG <3 g/L has been converted to 3 g/L in the graph.

Figure 3 Diagnosis of patients with globulin levels ≤ 16 g/L.

Figure 4 Hematology subgroups.

Figure 5 Follow-up details on patients with globulin ≤ 16 g/L, idiopathic hypogammaglobulinemia.

Table 2 Summary of Diagnostic Outcomes

Diagnosis	Globulin Level at Diagnosis	Outcome
Light chain myeloma	14 g/L	Identified during the course of the study, presented with severe back pain on morphine treatment. Died prior to initiation of treatment for myeloma.
Light chain myeloma	<16 g/L	Identified in the previous 9 years by reflex testing. All six patients were reviewed by hematology specialists; four with light chain MGUS were placed under observation, and treatment initiated for two patients with light chain myeloma.
Non-secretory myeloma	14 g/L	Two patients identified by reflex testing during the course of the study, treatment was commenced for non-secretory myeloma by hematology specialists.
Possible Good syndrome	15 g/L	Frail patient assigned to conservative treatment.
CVID	<16 g/L	Three patients identified with globulin < 16 g/L in 2019, were identified in the previous 9 years by reflex testing. Treatment was initiated by immunology specialists following diagnosis of CVID.
“Idiopathic hypogammaglobulinemia”	<16 g/L	This cohort included transient hypogammaglobulinemia and those with co-existing morbidities. In this group 33% were further investigated either by specialists in immunology or hematology, or by antibody response to vaccines. The group were either assigned to monitoring should symptoms develop or advised on vaccination schedules or antibiotic treatment. Patients who had a delayed diagnosis of non-secretory myeloma, possible Good syndrome or possible CVID were allocated to this group prior to further investigation and diagnostic testing.
SID	<16 g/L	The group included patients with immunoparesis secondary to hematological malignancies or immunosuppressant or antiepileptic drug therapy. The latter two groups were more likely to be detected by reflex testing and less prone to be reviewed for SID.