Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

Table 1 Studies of hepatitis B virus reactivation in patients receiving chimeric antigen receptor-T cell therapy

Ref.	Indication for CAR-T	N	CHB, n	Past resolved HBV infection, n	Antiviral prophylaxis, % patients	Definition of HBV reactivation	Rate of HBV reactivation	HBV-related death
Prospective studies
Liu et al[87], 2020	B-cell lymphoma	17	6	11	100% for CHB, and 45.5% for past infection (entecavir)	Elevation of HBV DNA levels to > 1000 IU/mL and/or HBsAg reverse seroconversion in HBsAg-negative patients	0	0
Yang et al[89], 2020	DLBCL	15	15	0	100% (lamivudine, entecavir, tenofovir, or adefovir dipivoxil)	Positive follow-up HBV-DNA test if the baseline HBV-DNA is undetectable/negative or > 10-fold increase from baseline	20%	0
Li et al[86], 2021	ALL, B-cell lymphoma	30	0	30	No prophylaxis	Elevation of HBV DNA ≥ 100 IU/mL for two consecutive measurements	6.6%	0
Wang et al[88], 2020	ALL, B-cell lymphoma, PCM	70	12	29	100% for CHB (entecavir, tenofovir disoproxil, or lamivudine). Nil for patients with past HBV infection	> 1 log increase in HBV DNA, HBV DNA-positive when previously negative, HBV DNA > 2000 IU/mL if no baseline level was available, or reverse sero-conversion from HBsAg-negative to positive	16.7% with chronic infection and 34.4 % with past infection	0
Retrospective studies
Cao et al[83], 2020	ALL, NHL	89	19	37	100% for chronic infection, and 5.4% for past infection	100-fold increase in HBV DNA when compared with baseline or HBV DNA ≥ 103 IU/mL in a patient with a previously undetectable level or reverse seroconversion from HBsAg negative to HBsAg positive	5.3% for CHB	0
Han et al[85], 2020	Multiple myeloma	9	1	8	100% for CHB, 25% for past infection (lamivudine/entecavir)	HBsAg seroconversion or increase in HBV DNA levels by at least 10-fold or 1 × 109 copies/mL	12.5% for past infection	0
Cui et al[84], 2021	DLBCL, B-ALL	20	5	15	100% for CHB (entecavir or tenofovir), 13.3% for past HBV infection (entecavir)	For CHB: (1) ≥ 2 log increase in HBV DNA compared to the baseline level; (2) HBV DNA ≥ 3 log IU/mL in a patient with previously undetectable level; and (3) HBV DNA ≥ 4 log IU/mL if the baseline level is not available. For resolved HBV infection: HBV DNA is detectable; reverse HBsAg seroconversion	6.2% for past infection	0

AASLD: American Association for the Study of Liver Diseases; ALL: Acute lymphoblastic leukemia; CAR: Chimeric antigen receptor; CHB: Chronic hepatitis B; CLL: Chronic lymphocytic leukemia; DLBCL: Diffuse large B-cell lymphoma; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; NHL: Non-Hodgkin lymphoma; PCM: Plasma cell myeloma.