Table 4 Adverse effects of CAR-T therapy

Prolonged cytopenia (lasting > 30 days)

28%²⁷

32%²⁶

Observed even in absence of lymphodepletion^37,99

Probably due to CAR-T influence

Resolved up to 6 months²⁶

Hypogammaglobulinemia

15%²⁷

27–46%⁹⁵

B-cell aplasia reported in 98% of PTS⁹⁵ and is not necessary associated with hypogammaglobulinemia

Infections

22.6%^95a

14%^95b

No difference in the rate of infections and their etiology compared to other anti-cancer therapies

Bacterial^a and viral^b etiology predominated

Risk factors—ALL, sCRS, CAR-T dose, number of prior therapy lines

Vector-associated complications: malignancy clonally related to modified cells (genotoxicity) or formation of Replication Competent Retroviruses (RCR)

—

RCPs reported in early studies¹⁰⁰

Genotoxicity reported for other cell therapy^{101,102,103,104} even 15 years after treatment¹⁰⁵

Not reported after CAR-T therapy probably due to (1) the use of vectors with less potent viral promoters (↓genotoxicity) and reduced recombination rate (↓RCR formation), (2) testing of cell product for RCRs, (3) lack of follow-up

Tumor lysis syndrome (TLS): metabolic disorder associated with massive release of tumor cell debris (hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia)¹⁰⁶

4% (all grade 3)¹

14% (2/14 pts)¹⁰⁷

1 death²

1 death¹⁰⁸

Common in any type of anti-cancer therapy

May contribute to other complications (e.g., acute renal failure due to CRS¹⁰⁹)

Risk factors—tumor burden, high proliferation rate, and highly responsive to treatment disease¹¹⁰

Multiple guidelines available^{110,111,112,113}

Anaphylactic shock and anti-transgene immune response

0%¹¹⁴

25%¹¹⁵

scFvs mostly derived from murine antibodies (immunogenic)

Anaphylaxis case (IgE associated)¹¹⁵ observed in 1 of 4 PTS receiving multiple infusions of CAR-Ts. Not reported by another group (n = 47)¹¹⁴

Cases of anti-CAR antibodies¹¹⁶ or anti-CAR cellular response^11,117 leading to decreased persistence and lack of clinical response

Graft-versus-host disease (GVHD) after donor-derived CAR-T infusion in PTS relapsed after allo-HSCT

—

No cases of GVHD^99,118

2 of 9 PTS experienced GVHD grade 3–4¹⁰⁸