Table 1. FDA-approved CAR T-cell therapies and hypogammaglobulinemia and infections.

Data for each of the FDA-approved CAR T-cell products, including hypogammaglobulinemia (all grades and grades ≥ 3), infections (all grades and grades ≥ 3), infection types, treatments, population and malignancy demographics, and additional notes on each product. Data gathered from applications submitted to the FDA.

		Hypogammaglobulinemia		Infections		Infection Types
Target/Agent/Manufacturer*	Population / Malignancy	All Grades, n (%)	Grade ≥ 3, n (%)	All Grades N (%)	Grade ≥ 3, N (%)	Infection Types	All Grades N (%)	Grade ≥ 3, N (%)	Hypogammaglobulinemia treatment	Notes
CD19 CAR-T, Tisagenlecleucel (Kymriah, Novartis) 45	Ages 3–23 years (safety set) relapsed/refractory B-cell precursor ALL	20 (29%) (Post-CAR-T time period)	3 (4%) (Post-CAR-T time period)	40 (59%)	19 (27%)	Not specified	% not specified	% not specified	Patients maintained on supplemental treatment with intravenous gamma globulin (IVIG) post-tisagenlecleucel. Prolonged hypogammaglobulinemia necessitated the use of routine infusions of IVIG.	Hypogammaglobulinemia reported in 24 of 68 patients in the safety set pre- and post- infusion of tisagenlecleucel
CD19 CAR-T, Axicabtagene ciloleucel (Yescarta, Kite Pharma) 46	108 adult patients with relapsed or refractory aggressive B-cell non-Hodgkin (primary safety population for ZUMA-1)	16 (15%) (unclear if post-CAR-T rate)	0%	41 (38%), serious infections	25 (23%)	Unspecified: Viral Bacterial Lung Fungal	28 (26%) 17 (16%) 14 (13%) 13 (12%) 5 (5%)	17 (16%) 4 (4%) 10 (9%) 11 (10%) 0 (0%)	Patients were maintained on supplemental treatment with intravenous gamma globulin. (6% of patients were started on immunoglobulins following the first dose of KTE-C19 & prior to hospital discharge)	Hypogammaglobulinemia following YESCARTA occurred in 15% of patients and required monitoring and intervention
CD19 CAR-T, Lisocabtagene maraleucel (Breyanzi, Juno Therapeutics) 47	Age > 18 y/o; Adult patients with relapsed or refractory (R/R) large B-cell lymphoma after at least 2 prior therapies	32% (defined as IgG <500 mg/dl)	0%	45% (121/268)	19% (52/268)	Unspecified Bacterial URTI Viral	29% 13% 13% 10%	16% 5% 0.7% 1.5%	Intravenous immune globulin (IVIG) therapy was not mandated in the protocol for a defined IgG cutoff level and was left to clinician discretion. As the vast majority of subjects with hypogammaglobulinemia did not receive IVIG, IVIG replacement can be left to institutional clinical practice and judgment	The analysis of IVIG replacement therapy by the company included all events of hypogammaglobulinemia based on laboratory analyses during the study and was not restricted to the treatment emergent period.
CD19 CAR-T, Brexucabtagene autoleucel (Tecartus, Kite Pharma) 48	Adult patients with relapsed/refractory mantle cell lymphoma. 82 pts received treatment in the safety population (ZUMA-2)	12 (15%)	1 (1%) (Grade 3 or higher)	47 (57%)	26 (32%)	Unspecified Viral Bacterial Pneumonia Fungal	35 (43%) 14 (17%) 13 (16%) 15 (17%) 8 (10%)	23 (28%) 4 (5%) 6 (7%) 10 (12%) 0 (0%)	Hypogammaglobulinemia can persist for months and requires monitoring and intervention	Hypogammaglobulinemia risks managed with appropriate risk mitigation strategies.
BCMA CAR-T, Idecabtagene vicleucel (Abecma, Celgene Corporation) 49	Adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy	41% (52/127) of subjects	0.80%	89 (70%)	29 (23%)	Unspecified Bacterial Viral Pneumonia URTI	(%) 51 15 27 17 34	(%) 15 3.9 9.4 9.4 1.6	Overall, 77/127 (61%) of ABECMA treated subjects received IVIG (intravenous immunoglobulin) therapy for serum IgG level less than 400 mg/dl as needed to maintain an IgG level above 400 mg/dl.	Newly diagnosed hypogammaglobulinemia, based either on laboratory value defined as IgG <500 mg/dl post-ABECMA infusion or an adverse event was reported in 41% (52/127) of subjects

^*The commercial trade name is provided in parentheses with manufacturer