Table 4.

Unmet needs and future research for HSRs to rituximab.

Classification	Clear and acceptable classification for the type of reaction
	Well defined criteria for this classification
	Clear clinical and laboratory criteria to differentiate the type of reactions
	Effective biomarkers for clear endotyping underlying reactions
Epidemiology	Lack of data about morbidity and mortality of each type of reactions
RISS*	Clinical trials in such patients with allergist involvement to obtain better evidence for the diagnostic criteria and management
SCARs**	Clearly understanding the mechanism and diagnostic methods
	The differential diagnosis in case of exposure to other concomitant medications that are known to cause SCARs
Skin tests	Non-irritant dose of rituximab
	The high cost of rituximab to use for skin tests
	Lack of skin test reagents containing all the immune epitopes
	Perfect timing for doing skin tests after an HSR
	Role of skin test in the prediction of breakthrough reactions
	The role of patch test in the diagnosis of delayed-type reaction
In vitro tests	Their roles in diagnosis
Desensitization	Optimal premedication protocols
	Candidates for desensitization
Cross-reactivity	Between rituximab, obinutuzumab, ofatumumab, veltuzumab and ocrelizumab
OVERALL	A multidisciplinary team study including allergists, pharmacologists, nurses, oncologists, hematologists, and other specialties to improve the diagnostic approach and management of HSR s to mAbs and to overcome the unmet needs

*Rituximab induced serum sickness, **Severe cutaneous adverse reaction.