CD19 x CD3 BiTEs for Acute Lymphoblastic Leukemia — An Interview with Dr Bijal Shah

·1 hr 3 min·5 clips

Dr. Shah reveals how blinatumomab achieved complete remissions in patients where historic therapies had failed entirely.

Dr. Neil Love hosts Dr. Bijal Shah from Moffitt Cancer Center to discuss CD19-directed bispecific T-cell engagers for acute lymphoblastic leukemia. The episode begins with the history of blinatumomab, approved in 2014, which transformed outcomes for relapsed/refractory ALL, shifting survival from 3-5% to achieving complete remissions. Dr. Shah explains how blinatumomab moved into minimal residual disease settings, improving cure rates to around 50%, and then into frontline therapy via the ECOG-1910 study, now recommended for all CD19-positive B-ALL patients. A technical segment clarifies that blinatumomab is a BiTE (bispecific T-cell engager) stripped of its Fc portion, unlike newer bispecific antibodies like mosunetuzumab which retain it. The discussion turns to extramedullary disease and central nervous system involvement, noting that conventional IV blinatumomab doesn't work in the CNS, but early data suggest newer antibodies like glofitamab may cross. Dr. Shah details two new agents: suravatamig, a human bispecific antibody with a silenced Fc and low-affinity CD3 binder, showing 70-80% response rates and deep MRD negativity in trials; and MK1045, another bispecific with similar structure and low toxicity rates. Three patient cases are presented. The first is a 59-year-old bed-bound woman with spastic quadriplegia and Philadelphia-positive ALL who achieved sustained remission after one cycle of blinatumomab and ponatinib. The second is a 50-year-old woman with TP53-mutated, hypodiploid ALL and extramedullary disease who relapsed after blinatumomab despite initial response, surviving 50 months. The third is a 52-year-old man with Pax5-rearranged ALL who failed multiple therapies but responded to suravatamig after CAR-T relapse. The episode concludes with comparisons of CAR-T products like brexucabtagene autoleucel and axicabtagene ciloleucel, and the importance of genomic risk stratification in ALL.

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