Low Dose Steroids Can Alleviate Blinatumomab-Associated Toxicities without Negatively Impacting Treatment Efficacy

Relapsed/refractory precursor B cell acute lymphoblastic leukemia (B cell ALL) carries a poor prognosis in adults and remains a challenging therapeutic area. Allogeneic stem cell transplantation is the only potentially therapeutic strategy for this group of patients, but its success depends on the disease status at the time of transplant. Blinatumomab is a recently approved bi-specific CD19-directed CD3 T-cell engager (BiTE) antibody in B-cell ALL patients who have failed induction chemotherapy. Its administration however is commonly complicated by grade III-IV toxicities including high-grade fevers and Cytokine Release Syndrome (CRS) defined as elevations in ferritin levels, pro-inflammatory cytokines such as IL-6, fever, chills and vascular leak. These complications can result in in premature treatment interruptions, failures as well as treatment-related mortality. At this time, it is unknown whether the concomitant use of steroids with Blinatumomab can alleviate these symptoms without negatively impacting the efficacy of treatment.

Here we describe two patients who were treated with standard dosing of Blinatumomab starting at 9 mcg/day on days 1-7 and 28 mcg/day on days 8-28. Both patients developed grade III-IV febrile episodes within the first 24 hours of treatment resulting in initial treatment interruption. These febrile episodes were associated with elevations in ferritin level. After a brief supportive measure, Blinatumomab was restarted but this time concurrently with methyl-prednisolone 5-10mg BID for days 2-5. Neither patient required any further treatment interruption or developed CRS as measured by normal IL-6 levels. In both cases a complete remission was achieved and they were successfully bridged to allogeneic stem cell transplantation.

In conclusion, in relapsed and refractory B-cell ALL, Blinatumomab-associated grade III/IV toxicities may be successfully addressed with low dose steroids without inhibiting anti-leukemic effect of BiTE antibody.