Outpatient Management of Bispecific Related Toxicities: An Observational Study of Safety Outcomes and Resource Utilization

Cytokine release syndrome (CRS) commonly occurs during initiation of bispecific T-cell engaging therapy (BsAbs) for multiple myeloma (MM) (NEJM 2022;387:495, NEJM 2022;387:2232, Nat Med 2023;29:2259). Pre-medications, step-up dosing (SUD), and monitoring minimize high-grade toxicity risk, while protocolized outpatient (OP) management of BsAbs and toxicities could reduce resource utilization and improve patient satisfaction. At Mayo Clinic, SUD, clinical assessment and grade 1 CRS management occurs primarily as an OP for patients with MM receiving BsAbs.

This study aims to assess the current OP management practices of BsAbs and related toxicities including patient outcomes, admission rates, and resource utilization. Patients with MM who received SUD from August 23, 2023, to March 29, 2024, were included. Baseline demographics, patient outcomes, and CRS management details are summarized. Resource utilization outcomes included level of care, length of hospital stay (LOS), and high-cost drug administration.

38 patients received MM BsAbs during the study timeframe. 34 patients initiated OP SUD (teclistamab n=17 and talquetamab n= 17). The median age was 71 years, 59% were male, 82% were white, and 88% had Medicare coverage. Median number of prior lines of therapy was 6.

There were 317 OP encounters with a median of 10 encounters per patient. Of these, 72% were planned in-person assessments, 5% were unplanned clinic visits for potential toxicity-related symptom assessment, and 20% were phone visits that obviated in-person assessment. 66 of 68 doses of talquetamab (total of 1,628 mg) and 48 of 50 doses of teclistamab (total of 2,048 mg) were administered and billed in the OP setting.

24 patients (71%) that initiated OP SUD developed CRS (grade 1 n=16, grade 2 n=7). Management of the initial CRS event included steroids and acetaminophen, with or without tocilizumab. 2,600 mg of tocilizumab administered in the OP setting. Recurrent CRS was seen in 5 patients and also treated entirely OP. 4 patients developed ICANS (grade 1 n=3, grade 3 n=1).

Hospitalization following OP SUD initiation occurred in 18 (53%) patients at some point during treatment. Indications included grade 2 CRS (n=6), ICANS (grade 1 n=3), refractory CRS (n=7), infection (n=1), GI bleed (n=1), planned observation for comorbidities or prior CRS (n=2), loss of caregiver (n=1), atrial fibrillation (n=1), heart failure (n=1), and pain crisis (n=1). Median LOS was 2 days. Recurrent admission occurred in 41% and median LOS was also 2 days for subsequent admissions. Two patients were admitted to the intensive care unit for hypotension or arrhythmia. 1 patient required dialysis.

In total for SUD during the study time frame, 51 mg of teclistamab, 176 mg of talquetamab, and 8,240 mg of tocilizumab were billed under an IP encounter, which likely was due to inpatient administration or hospital admission within 72 hours of receiving the OP SUD.

This descriptive study of our OP BsAb management practice demonstrated that 47% of patients remained OP, even with a CRS event. The CRS rate did not surpass those in landmark clinical trials and aligns with real-world data previously reported (Blood Cancer J 2024;14:35.). Availability and use of patient monitoring capabilities along with lack of sentinel outcomes emphasizes the safety of an OP BsAb practice. Drivers of financial burdens and savings include location and reimbursement of high-cost drugs and admission rates. Median LOS was less than half of what's anticipated with inpatient SUD. Inpatient administration of high-cost drugs can be more costly compared to OP due to associated medical costs and insufficient reimbursement in a population primarily insured by Medicare which reimburses inpatient mediations based on the Diagnostic Related Group (DRG) unless the medication has New Technology Add on Payment (NTAP). Using expected Medicare reimbursement rates and wholesale acquisition costs while excluding variable DRG reimbursement and NTAP impacts for teclistamab, the total net revenue improvement for shifting use of all teclistamab, talquetamab, and tocilizumab OP is $115,004 for the period analyzed (CMS.gov 2024).

In conclusion, OP management of patients undergoing SUD for MM BsAbs is safe and has substantial reductions in resource utilization and costs.

Sandahl:Johnson & Johnson: Consultancy; BioLineRx: Consultancy; Pfizer Inc: Consultancy. Jensen:Aptiitude Health Cases: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy. Kapoor:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Loxo Pharmaceuticals: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; Ichnos: Research Funding; Bristol Myers Squibb: Research Funding; Regeneron: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy; Keosys: Consultancy. Dingli:Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; K36 Therapeutics: Research Funding; Apellis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Sorrento: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Kumar:MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Other: Independent review committee participation; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Sanofi: Research Funding. Kourelis:Pfizer: Research Funding; Novartis: Research Funding. Cook:Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Lin:Janssen: Consultancy, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Legend: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Consultancy; NexImmune: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Celgene: Consultancy, Research Funding.