Allergy to monoclonal antibodies: cutting-edge desensitization methods for cutting-edge therapies

Figures & data

Figure 1. The prevalence of hypersensitivity reactions is reduced with rapid desensitization.

(A) Breakdown of initial presenting reactions for which patients were referred for desensitization. (B) Prevalence of reactions with desensitization.

CUT: Cutaneous; CVR: Cardiovascular; F/C: Fever/chills; GI: Gastrointestinal; N-M: Neurologic/muscular; RESP: Respiratory; THROAT: Throat tightness.

Adapted with permission from [5].

Table 1. Rituximab desensitization protocol: standard three-solution, 12-step protocol.

Step	Solution	Rate (ml/h)	Time (min)	Volume infused per step (ml)	Dose administered with this step (mg)	Cumulative dose (mg)
1	1^†	2.0	15	0.50	0.0221	0.0221
2		5.0	15	1.25	0.0553	0.0774
3		10.0	15	2.50	0.1106	0.1880
4		20.0	15	5.00	0.2212	0.4092
5	2^‡	5.0	15	1.25	0.5530	0.9622
6		10.0	15	2.50	1.1060	2.0682
7		20.0	15	5.00	2.2120	4.2802
8		40.0	15	10.00	4.4240	8.7042
9	3^§	10.0	15	2.50	10.9730	19.6772
10		20.0	15	5.00	21.9459	41.6231
11		40.0	15	10.00	43.8918	85.5149
12		80.0	174.375	232.50	1020.4851	1106.0000

^†Solution 1: 250 ml of 0.044 mg/ml (total per bag: 11.060 mg).

^‡Solution 2: 250 ml of 0.442 mg/ml (total per bag: 110.600 mg).

^§Solution 3: 250 ml of 4.389 mg/ml (total per bag: 1097.296 mg).

Target dose: 1106.0 mg; standard volume per bag: 250 ml; final rate of infusion: 80 ml/h; calculated final concentration: 4.424 mg/ml; standard time of infusion: 187 min; total time: 339.375 min (5.66 h). The total volume and dose dispensed are more than the final dose given to the patient because many of the solutions are not completely infused.

Adapted with permission from [5].

Table 2. Infliximab desensitization protocol for a patient who had recurrent urticaria at step 11 refractory to additional antihistamine^†.

Step	Solution	Rate (ml/h)	Time (min)	Volume infused per step (ml)	Dose administered with this step (mg)	Cumulative dose (mg)
1	1^‡	2.0	15	0.50	0.0118	0.0118
2		5.0	15	1.25	0.0296	0.0414
3		10.0	15	2.50	0.0591	0.1005
4		20.0	15	5.00	0.1182	0.2187
5	2^§	5.0	15	1.25	0.2956	0.5143
6		10.0	15	2.50	0.5912	1.1055
7		20.0	15	5.00	1.1824	2.2879
8		40.0	15	10.00	2.3648	4.6527
9	3^¶	10.0	15	2.50	5.8655	10.5182
10		20.0	15	5.00	11.7309	22.2492
11		40.0	15	10.00	23.4619	45.7111
11a		60.0	15	15.00	35.1928	80.9039
12		80.0	174.375	232.50	545.4889	591.2000

^†A three-solution, 13-step protocol was developed. Note the addition of step 11a.

^‡Solution 1: 250 ml of 0.024 mg/ml (total per bag: 5.912 mg).

^§Solution 2: 250 ml of 0.236 mg/ml (total per bag: 59.120 mg).

^¶Solution 3: 250 ml of 2.346 mg/ml (total per bag: 586.547 mg).

Target dose: 591.2 mg; standard volume per bag: 250 ml; final rate of infusion: 80 ml/h; calculated final concentration: 2.3648 mg/ml; standard time of infusion: 187.5 min; total time: 354.375 min (5.91 h).

Adapted with permission from [5].

Table 3. Etanercept desensitization protocol for a patient with hypersensitivity to both adalimumab and etanercept.

Step	Time interval from previous step (min)	Dose (mg)	Dilution	Volume administered (ml)
Day 1^†
1	0	0.25	1:100	1
2	30	0.5	1:10	0.2
3	60	1	1:10	0.4
4	60	2	1:10	0.8
5	90	4	1:1	0.16
6	120	4.5	1:1	0.18
Day 2^‡
1	0	0.25	1:100	1
2	30	0.5	1:10	0.2
3	60	1	1:10	0.4
4	60	2	1:10	0.8
5	90	4	1:1	0.16
6	120	4.5	1:1	0.18
Day 3^§
1	0	0.25	1:100	1
2	30	0.5	1:10	0.2
3	60	1	1:10	0.4
4	60	2	1:10	0.8
5	90	4	1:1	0.16
6	120	8	1:1	0.32
7	150	8.75	1:1	0.35
Maintenance dosing (twice weekly)
1	NA	25	1:1	1

^†Total dose administered: 12.25 mg.

^‡Total dose administered: 12.25 mg.

^§Total dose administered: 25 mg.

Etranercept desensitization standard dilution: 25 mg/ml.

Data from [23].

Table 4. Cetuximab desensitization protocol: one-solution, five-step protocol.

Step	Solution	Rate (ml/h)	Time (min)	Volume infused per step (ml)	Dose administered with this step (mg)	Cumulative dose (mg)
1	1^†	5.0	30	2.50	5.0658	5.0658
2		10.0	30	5.00	10.1316	15.1974
3		20.0	30	10.00	20.2632	35.4606
4		40.0	30	20.00	40.5264	75.9870
5		80.0	256.87	342.49	694.0011	769.9881

^†Solution 1: 380 ml of 2.026 mg/ml (total per bag: 770.002 mg).

Target dose: 770.0 mg; standard volume per bag: 250 ml; final rate of infusion: 80 ml/h; calculated final concentration: 3.08 mg/ml; standard time of infusion: 187.5 min; total time: 376.87 min (6.28 h).

Table 5. Trastuzumab desensitization protocol: standard three-solution, 12-step protocol.

Step	Solution	Rate (ml/h)	Time (min)	Volume infused per step (ml)	Dose administered with this step (mg)	Cumulative dose (mg)
1	1^†	2.0	15	0.50	0.0115	0.0115
2		5.0	15	1.25	0.0288	0.0403
3		10.0	15	2.50	0.0575	0.0978
4		20.0	15	5.00	0.1150	0.2128
5	2^‡	5.0	15	1.25	0.2875	0.5003
6		10.0	15	2.50	0.5750	1.0753
7		20.0	15	5.00	1.1500	2.2253
8		40.0	15	10.00	2.3000	4.5253
9	3^§	10.0	15	2.50	5.7047	10.2300
10		20.0	15	5.00	11.4095	21.6395
11		40.0	15	10.00	22.8190	44.4585
12		80.0	174.375	232.50	530.5415	575.0000

^†Solution 1: 250 ml of 0.023 mg/ml (total per bag: 5.750 mg).

^‡Solution 2: 250 ml of 0.230 mg/ml (total per bag: 57.500 mg).

^§Solution 3: 250 ml of 2.282 mg/ml (total per bag: 570.475 mg).

Target dose: 575.0 mg; standard volume per bag: 250 ml; final rate of infusion: 80 ml/h; calculated final concentration: 2.3 mg/ml; standard time of infusion: 187.5 min; total time: 339.375 min (5.66 h).

Adapted with permission from [5].

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