Anti-BCMA CAR-T Cell Therapy in Relapsed or Refractory Multiple Myeloma Patients with Impaired Renal Function

Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.

Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders:phase 1 trial interim results

Chimeric antigen receptor(CAR)T-cell therapy that targets B-cell maturation antigen(BCMA)have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder(NMOSD).To evaluate the safety and efficacy of the CT103A,a self-developed BCMA-targeting CAR construct against BCMA,in patients with AQP4-IgG seropositive NMOSD,an ongoing,investigator-initiated,open-label,single-arm,phase 1 clinical trial is conducted at our center.In total,12 patients were administered with a CAR-BCMA infusion.Ten of the 12 patients dosed were women(83.3%),with a median age of 49.5 years(range,30-67).were The most common events of grade 3 or higher were hematologic toxic effects.Seven patients(58%)developed infections,but no grade 4 infections occurred.Cytokine release syndrome was reported in all patients with only events of grade 1 or 2 observed.During the follow-up of a median 5.5 months,11 patients had no relapse;all patients generally reported improvement in disabilities and quality-of-life outcomes;11 patients’AQP-4 antibodies in serum showed a downward trend by the cutoff date.CAR T-cell expansion was associated with responses,and persisted more than 6 months post-infusion in 17%of the patients.In summary,CAR T-cell therapy shows a manageable safety profile and therapeutic potentials for patients with relapsed/refractory AQP4-IgG seropositive NMOSD.Another expansion phase is currently underway to determine the safety and efficacy of CAR T-BCMA infusion in patients with other neuro-inflammatory diseases.