Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study

Figures & data

Table 1. Baseline patient, disease and treatment characteristics of sub-groups by infections during IsaPomDex (any grade infections vs. no infections).

Baseline characteristics			Subgroups by infections during IsaPomDex treatment, from total cohort n = 107
			Any grade infections n = 25	No infections n = 82	P value
Patient	Age (years)	(median, range, IQR)	67 (34–87, 60–77.5)	69.5 (33–85, 61–76)	0.66
	Months since Dx	(median, range, IQR)	55 (13–124, 36.5–78)	54 (10–237, 38–86)	0.79
	Sex	Male	20 (80%)	48 (58.5%)	0.06
		Female	5 (20%)	34 (41.5%)
	Performance status*	<2	19 (76%)	67 (81.7%)	0.453
	Co-morbidities (CCI score)	Median (range, IQR)	2 (0–8, 2–4)	3 (0–12, 2–4)	0.77
		CCI <4	12 (48%)	51 (62.2%)	0.843
		CCI ≥4	13 (52%)	31 (37.8%)
	Lymphopenia	Yes	13 (52%)	37 (45.1%)	0.546
	Anaemia	Yes	20 (80%)	62 (75.6%)	0.79
	Hypercalcaemia	Yes	2 (8%)	10 (12.2%)	0.728
	(e-GFR < 60 ml/min)	Yes	6 (24%)	40 (48.8%)	0.028
Disease	MM subtype	Ig (G/A/M/D)	21 (84%)	62 (75.6%)	0.584
		Light chain	4 (16%)	20 (24.4%)
	Elevated LDH*	Yes	6 (24%)	31 (37.8%)	0.402
	ISS staging*	1	4 (16%)	20 (24.4%)	1.0
		2	6 (24%)	27 (32.9%)
		3	5 (20%)	23 (28%)
	Cytogenetic Risk*	High risk (HR)	6 (24%)	9 (11%)	0.21
		Standard risk (SR)	11 (44%)	36 (43.9%)
	EM disease	Yes	6 (24%)	10 (12.2%)	0.147
Prior therapies	Number of therapies	Median (range, IQR)	3 (2–4, 3–3)	3 (2–5, 3–3)	0.887
	Prior transplant	Yes	16 (64%)	49 (59.8%)	0.704
	Prior alkylator	Yes	0 (0%)	16 (19.5%)	1.0
	Prior PI	Yes	25 (100%)	81 (98.8%)	1.0
	Prior IMiD	Yes	25 (100%)	82 (100%)	NA
	Prior anti-CD38	Yes	1 (4%)	4 (4.9%)	1.0
	Prior HDACi	Yes	1 (4%)	3 (3.7%)	1.0
IsaPomDex	Number of cycles	Median (range, IQR)	5 (1–15, 2–11)	4 (1–15, 2–7)	0.268
		<4	10 (40%)	38 (46.3%)	0.133
		≥4	15 (60%)	44 (53.7%)
	Ongoing	Yes	14 (56%)	59 (72%)	0.134
	Pom dose reduction	Yes	10 (40%)	33 (40.2%)	0.983
	Dex dose reduction	Yes	10 (40%)	34 (41.5%)	0.896
	Anti-viral PPx*	Yes	23 (92%)	76 (92.7%)	1.0
	Anti-fungal PPx*	Yes	17 (68%)	70 (85.4%)	0.082
	PCP PPx*	Yes	17 (68%)	39 (47.6%)	0.036

Abbreviations: Isa (isatuximab), Dex (dexamethasone), Pom (pomalidomide), Dx (diagnosis), PS (performance status), NK (not known), CCI (Charlson co-morbidity index), LDH (lactate dehydrogenase) EM: extramedullary, MM (multiple myeloma), ISS (international staging system for MM), EM (extramedullary disease), PI (proteasome inhibitor), IMiD (immunomodulatory drug), HDACi (histone deacetylase inhibitor), IsaPomDex (isatuximab with pomalidomide and dexamethasone), PPx (prophylaxis), PCP (pneumocystis pneumonia). High risk cytogenetics is defined as one or more of the following features: t (4;14), t (14;16), del(17p).

*In the total cohort of 107 patients, the number of patients with NK data was: 1 for PS, 37 for LDH, 22 for ISS, 45 for cytogenetics, 66 for R-ISS, 1 for *antifungal PPx and 1 for PCP PPx.

Table 2. Infection episodes experienced during IsaPomDex treatment.

Nature of infection	Number of infection episodes during IsaPomDex in the total cohort
	Any grade (G2–5)	≥G3 (G3–5)
COVID-19 pneumonia	6	6
Neutropenic sepsis	5	5
E.coli infection	2	2
Urinary tract infection*	4	3
Lung infection (bacterial)’	5	2
Serratia liquifaciens infection	1	1
Pseudomonas sepsis	1	1
Bacteraemia**	1	1
Skin infection*	1	1
Pseudomonas infection	1	0
infection of unknown source*	1	0
GI infection*	1	0
Penile infection*	1	0
Viral infection*	1	0
Total	31	22

*For these infection episodes, data collection either did not include the site of the episode in some cases, or the responsible pathogen in other cases.

**Klebsiella was the responsible pathogen for bacteraemia reported in this cohort.

Table 3. Univariate and multivariate Poisson regression: all grade infections in the total cohort after a median of 4 IsaPomDex cycles.

Outcome	Characteristic	Univariate analysis				Multivariate analysis
		Rate	Incidence Rate Ratio	95% CI	P-value	Rate	Incidence Rate Ratio	95% CI	P-value
All infections from start of IsaPomDex Poisson regression**	Age (≥75 vs. <75 years)	≥75: 0.42 <75:0.25	1.7	0.69–4.23	0.252	–	–	–	–
	CCI categories (≥4 vs. <4)	≥4: 0.39 <4: 0.24	1.58	0.7–3.6	0.274	–	–	–	–
	Lymphopenia at baseline (Y vs. N)	Y: 0.31 N: 0.27	1.15	0.52–2.52	0.73	–	–	–	–
	ISS at baseline* (Ref: ISS 1)	ISS 1: 0.13 ISS 2:0.29 ISS 3: 0.22 UNK: 0.62	ISS 2: 2.2 ISS 3:1.7 UNK:4.68	ISS 2: 0.66–7.37 ISS 3: 0.55–5.29 UNK:1.83–11.98	ISS 2: 0.201 ISS 3: 0.361 UNK: 0.001	–	–	–	–
	e-GFR (≥60 vs <60)	≥60: 0.3 <60: 0.27	1.08	0.39–3.01	0.885	–	–	–	–
	Baseline LDH* (Ref: normal)	Normal: 0.33 High: 0.18 UNK: 0.36	High: 0.53 UNK: 1.08	High: 0.18–1.59 UNK: 0.46–2.55	High: 0.257 UNK: 0.857	–	–	–	–
	Pomalidomide dose attenuation	Y: 0.34 N: 0.25	1.38	0.64–2.99	0.417	–	–	–	–
	Dexamethasone dose attenuation	Y: 0.3 N: 0.28	1.08	0.5–2.37	0.841	–	–	–	–
	Myeloma response (≥PR)**	≥PR: 0.23 <PR: 0.44	0.51	0.22–1.18	0.115	–	–	–	–

Abbreviations: CCI (Charlson Co-morbidity Index), ISS (International Staging System), e-GFR (estimated glomerular filtration rate), LDH (lactate dehydrogenase), PR (partial response), NK (not known), Tx (treatment).

*From the total cohort of 107 patients, the number of patients with NK data was: 37 for LDH and 22 for ISS staging.

**Number of evaluable patients for response factor after a median of 4 treatment cycles, was 105.

Table 4. Univariate and multivariate Poisson regression: ≥G3 infections in the total cohort, after a median of 4 IsaPomDex cycles.

Outcome	Characteristic	Univariate analysis				Multivariate analysis
		Rate	Incidence Rate Ratio	95% CI	P-value	Incidence Rate Ratio	95% CI	P-value
≥G3 infections from Tx start (n = 107)*^ Poisson regression	Age (≥75 vs. <75 years)	≥75: 0.38 <75:0.0.15	2.58	1.04–6.37	0.040	–	–	–
	CCI categories (≥4 vs. <4)	≥4: 0.36 <4: 0.14	2.63	1.13–6.14	0.025	3	1.28–7.02	0.012
	Lymphopenia at baseline (Y vs. N)	Y: 0.19 N: 0.22	0.85	0.36–2.01	0.709	–	–	–
	ISS at baseline* (Ref: ISS 1)	ISS 1: 0.1 ISS 2:0.2 ISS 3: 0.18 NK: 0.41	ISS 2: 2.05 ISS 3: 1.81 NK: 4.16	ISS 2: 0.53–7.97 ISS 3: 0.49–6.7 NK:1.27–13.69	ISS 2: 0.298 ISS 3: 0.374 NK: 0.019	–	–	–
	e-GFR (≥60 vs <60)	≥60: 0.19 <60: 0.24	0.77	0.29–2.08	0.610	–	–	–
	Baseline LDH* (Ref: normal)	Normal: 0.23 High: 0.15 UNK: 0.24	High: 0.64 NK: 1.04	High: 0.2–2.08 UNK: 0.39–2.78	High: 0.457 UNK: 0.935	–	–	–
	Pomalidomide dose attenuation	Y: 0.19 N: 0.22	0.89	0.35–2.28	0.815	–	–	–
	Dexamethasone dose attenuation	Y: 0.17 N: 0.24	0.7	0.28–1.79	0.459	–	–	–
	Myeloma response (≥PR vs. <PR)*	≥PR: 0.15 <PR: 0.34	0.43	0.17–1.08	0.073	0.42	0.18–0.99	0.048

Abbreviations: CCI (Charlson Co-morbidity Index), ISS (International Staging System), e-GFR (estimated glomerular filtration rate), LDH (lactate dehydrogenase), NK (not known), PR (partial response), Tx (treatment).

*From the total cohort of 107 patients, the number of patients with NK data was: 37 for LDH and 22 for ISS staging.

**Number of evaluable patients for response factor after a median of 4 treatment cycles, was 105.

Table 5. Univariate logistic regression analysis: hospital admissions in the total cohort, after a median of 4 cycles of IsaPomDex.

Outcome	Characteristic	Univariate analysis
		Pearson chi square P value	Odds ratio (OR)	95% CI	Logistic P value
Hospital admissions (n = 107)**	Age (≥75 vs. <75)	0.523	1.36	0.53–3.5	0.524
	Co-morbidity CCI (<4 vs. ≥4)	0.255	0.87	0.36–2.13	0.765
	e-GFR (≥60 vs <60)	0.42	1.46	0.58–3.69	0.421
	Anaemia at baseline (Y vs. N)	0.125	2.69	0.73–9.9	0.136
	Lymphopenia at baseline (Y vs. N)	0.546	1.32	0.54–3.23	0.547
	LDH (elevated vs normal)*	0.268	0.54	0.18–1.63	0.271
	Number of chemo cycles (>4 vs ≤4)	0.133	1.99	0.8–4.92	0.137
	Pomalidomide dose (<4 mg vs. 4 mg)	0.363	1.52	0.62–3.75	0.364
	Dexamethasone dose (<100% vs. 100%)	0.425	1.44	0.59–3.55	0.426
	Infections (Y vs. N)	<0.001	138.25	28.7–666.12	<0.001

Abbreviations: CCI (Charlson Co-morbidity Index), ISS (International Staging System), e-GFR (estimated glomerular filtration rate), LDH (lactate dehydrogenase), NK (not known), PR (partial response), Tx (treatment).

*From the total cohort of 107 patients, the number of patients with NK data was: 37 for LDH.

**Number of evaluable patients for response factor after a median of 4 treatment cycles, was 105.

Figure 1. 3-month landmark analysis of overall survival (OS) according to infections in the first 3 months from starting IsaPomDex: (A) any grade infection vs. no infection, (B) ≥G3 infections vs. no infection.

Data availability statement

All available data relating to this report are presented in the manuscript and the accompanying tables.