Abstract

 

Background

Bispecific antibody initiation in relapsed/refractory MM (RRMM) is commonly associated with hospitalization

because of CRS, ICANS, and step-up dosing logistics. Emerging strategies, including outpatient or hybrid

initiation, condensed step-up schedules, and prophylactic toxicity-mitigation approaches, may reduce inpatient

burden, but evidence remains fragmented.

 

Methods

We systematically searched PubMed/MEDLINE, ClinicalTrials.gov, and major hematology/oncology conference

proceedings, including ASH, ASCO, EHA/HemaSphere, and SOHO, for studies evaluating strategies to reduce

hospitalization during bispecific antibody initiation in RRMM. Core strategy studies included outpatient or

hybrid initiation models, condensed or accelerated inpatient step-up schedules, and prophylactic CRS-mitigation

approaches. Supportive initiation-toxicity studies were reviewed to contextualize early adverse event timing.

Primary outcomes were hospitalization, inpatient transition or readmission, LOS, CRS, and ICANS. Pooled

descriptive estimates were generated for outpatient core cohorts.

 

Results

Among 77 screened records, 16 studies were included, comprising 6 core strategy studies and 10 supportive

studies. Across three outpatient core cohorts, outpatient step-up dosing was highly feasible, with step-up

completion in 99.3% (143/144); hospitalization or inpatient transition occurred in 28.0% (40/143), while any-grade

CRS and ICANS occurred in 36.4% (52/143) and 6.3% (9/143), respectively. These findings suggest that routine

inpatient initiation may not be necessary for carefully selected patients with RRMM. Condensed or accelerated

step-up strategies were associated with shorter LOS, including reductions in median LOS from 9 to 6 days and

in mean LOS from 9.2 to 7.6 days. Prophylactic tocilizumab-based approaches were associated with low CRS-

related readmission burden. Supportive studies consistently showed that CRS clustered during early step-up

dosing, supporting protocolized monitoring and risk-adapted management during initiation.

 

Conclusion

Hospitalization-reduction strategies during bispecific antibody initiation in RRMM appear feasible and clinically

meaningful. Outpatient or hybrid initiation, step-up schedule optimization, and prophylactic CRS-mitigation

approaches may reduce inpatient burden while maintaining acceptable early safety in selected cohorts. These

findings support risk-adapted outpatient implementation at experienced centers and suggest that routine inpatient

initiation may be avoidable for selected patients, although prospective comparative studies are needed.

 

ASCO: American Society of Clinical Oncology, ASH: American Society of Hematology, EHA: European Hematology

Association, CRS: cytokine release syndrome; ICANS: immune effector cell-associated neurotoxicity

syndrome, LOS: length of stay, MM: multiple myeloma, SOHO: Society of Hematologic Oncology

 

Keywords

MM, bispecific antibodies, outpatient initiation, step-up dosing, hospitalization