Table 1. Severe side effects in selected CD19‐CAR T cell trials
Identifier (Synonym)NCT02535364 (ROCKET)NCT02348216 (ZUMA‐1)NCT02435849 (ELIANA)NCT01865617NCT01864889
SponsorJuno TherapeuticsaKite PharmaNovartisFHCRCCPLA
IMPJCAR015KTE‐C19CTL019N.A.N.A.
CAR typeCD19/CD28/CD3zCD19/CD28/CD3zCD19/4‐1BB/CD3zCD19/4‐1BB/CD3zCD19/4‐1BB/CD3z
IndicationALLNHLALLALLALL, NHL
Included patientsN.A.5150299
Clinical outcomeN.A.47% CR82% CR90% CR55% CR
Dose (%CAR+ cells)N.A.2 × 106/kg (N.A.)2.9 × 106/kg (N.A.)2 × 106/kg (82%)≥ 3.0 × 106/kg (N.A.)
PersistenceN.A.Up to 12 months≥ 6 months> 8 monthsUp to 3 months
Conditioningcy + flu or cy aloneb

low‐dose

cy + flu

cy + flucy + fluOptional
Reported death cases

Three fatal cases of cerebral edema (cy + flu),

two fatal cases of cerebral edema (cy alone)

Two fatal cases due to CRSOne fatal case of intracranial hemorrhage prior to disease assessmentOne fatal case of irreversible neurologic toxicity 122 days after CAR T cell infusionOne fatal case of tumor lysis syndrome and one fatal case of GVHD
Neurological toxicities (grade ≥ 3)N.A.29% of treated patients15% of treated patients34% of treated patientsNot observed
References

DeFrancesco (2017),

press release

Neelapu et al (2016), Locke et al (2017)Grupp et al (2016)Turtle et al (2016)Dai et al (2015)
  • IMP, investigational medicinal product; ALL, acute lymphoid leukemia; NHL, non‐Hodgkin lymphoma; N.A., not available; CRS, cytokine‐release syndrome; cy, cyclophosphamide; flu, fludarabine; GVHD, graft‐versus‐host disease; SAEs, severe adverse events; CPLA, Chinese PLA General Hospital; FHCRC, Fred Hutchinson Cancer Research Center.

  • a Juno is using cyclophosphamide plus fludarabine pre‐conditioning treatment in other CAR T cell trials with the same or another IMP so far without reported cases of irreversible neurologic toxicities (NCT01044069, NCT01840566, NCT02028455, NCT02631044, NCT01865617). Notably, this trial has been discontinued due to neurologic toxicities.

  • b The conditioning regime was changed from cyclophosphamide plus fludarabine to cyclophosphamide alone upon the first death cases (DeFrancesco, 2016).