Siltuximab for the Prevention of CAR T Cell Related Cytokine Release Syndrome in Patients With CD19 Positive Non-Hodgkin Lymphoma

Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information

Age \>= 18 years at the time of consent

Diagnosis of non-Hodgkin lymphoma

Eligible for standard of care CD19.CAR-T cell therapy including axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel and lisocabtagene maraleucel)

Subjects with hepatitis B virus (HBV) can be included if on suppressive antiviral therapy and have no detectable viral load

Subjects with hepatitis C virus (HCV) can be included if HCV ribonucleic acid (RNA) viral load is undetected

Measurable disease of \> 1.5 cm in diameter and/or bone marrow involvement

White blood cell count \>= 1.0 x 10\^9/L (obtained within 14 days prior to initiating study treatment)

* Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

Hemoglobin \>= 8.0 x 10\^9/L (obtained within 14 days prior to initiating study treatment)

* Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

Platelets \>= 50 x 10\^9/L (obtained within 14 days prior to initiating study treatment)

* Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

Creatinine =\< 2.0 x upper limit of normal (ULN) (obtained within 14 days prior to initiating study treatment)

* Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

Bilirubin =\< 2.0 × upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \> 2.0 mg/dL if their conjugated bilirubin is =\< 2.0 × ULN) (obtained within 14 days prior to initiating study treatment)

Aspartate aminotransferase (AST) =\< 3.0 × ULN (obtained within 14 days prior to initiating study treatment)

* Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

Alanine aminotransferase (ALT) =\< 3.0 × ULN (obtained within 14 days prior to initiating study treatment)

* Note: Hematology and other lab parameters that are =\< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy

Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration

* NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided

Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 12 months after treatment the last dose of siltuximab. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets \< 1% failure rate for protection from pregnancy in the product label

Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 12 months after the last dose of siltuximab

Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the experimental regimen are eligible for the trial

Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee

FOR SILTUXIMAB TREATMENT OF CRS/ICANS: Any subject with grade 1 ICANS lasting \> 12 hours

FOR SILTUXIMAB TREATMENT OF CRS/ICANS: Any subject with grade \>= 2 CRS after CD19.CAR-T cell therapy

FOR SILTUXIMAB TREATMENT OF CRS/ICANS: Any subject with grade \>= 2 CRS after CD19.CAR-T cell therapy with concurrent ICANS

SECOND SILTUXIMAB TREATMENT DOSE FOR CRS/ICANS: Subjects meeting criteria for a treatment dose who have received a treatment dose and have no change in the CRS or ICANS grade after 12 hours

What this study is about