Reducing Infection Risks of Anti-BCMA Bispecific Antibodies in Multiple Myeloma: In-Hospital Vs. Hospital-at-Home Treatment
Authors: Winer Romain , Vignon Marguerite , Collier Mathis , Fouquet Guillemette , Hermine Olivier , Cazelles Clarisse , Frenzel Laurent , Choquet Sylvain , Garderet Laurent , Belhadj Merzoug Karim , Braun Thorsten , Bouscary Didier , Brandely-Piat Marie-Laure , Leclaire Clement , Gutierrez Maya , Moufle Frederique , Chauvin Cecile , Soulignac Arnaud , Zogo Arsene , Moreau Philippe , Zerbit Jeremie 
Published: December 2024

Introduction: Novel anti- B cell maturation antigen (BCMA) bispecific antibodies (BsAbs) have shown durable responses in multiple myeloma (MM) patients, but infections are common. Hospital at Home (HaH) is increasingly recognized in MM management. This study compares the outcomes of anti-BCMA BsAbs treatment in a real-world HaH setting versus inpatient care.

Materials and Methods: This study included all triple-class and penta-refractory MM patients treated with teclistamab or elranatamab at ten Greater Paris University Hospitals (AP-HP) from July 2022 to January 2024. Data were sourced from the AP-HP Clinical Data Warehouse. Patients treated in AP-HP HaH were compared with inpatients, using a 180-day landmark post BsAbs initiation. Patients were selected for HaH or inpatient care based on clinical criteria, including health status, stability, and patient preference. The primary endpoints were grade ≥ 3 infections and cytopenias. Secondary endpoints included survival and time to treatment failure.

HaH Settings: HaH patients received the first BsAb cycle in the hospital before transitioning to HaH. Before each home administration, HaH physicians and pharmacists reviewed biological results and clinical data. At-home monitoring included vital signs checks post-administration and clinical and biological assessments at 24 and 48 hours. Referring hematologists were alerted for issues according to an algorithm.

Patient Characteristics: The median follow-up was 13 months (IQR 9-16). The analysis included 176 inpatients (129 teclistamab, 47 elranatamab) and 25 HaH patients (19 teclistamab, 6 elranatamab). The median ages were similar (73 years for HaH, 72 years for inpatients), with more patients over 75 in the HaH group (36% vs. 25.6%). ISS stages I, II, and III were 28.0%, 24.0%, and 48.0% in HaH patients and 35.8%, 25.0%, and 39.2% in inpatients. Poor performance status (WHO 2-4) was reported in 32.0% of HaH patients and 46.6% of inpatients. Among HaH patients, 68% were penta-drug refractory versus 72.7% in inpatients. Bone lesions were present in 70% of HaH patients versus 79.5% of inpatients. High-risk cytogenetics were found in 12% of HaH patients and 24.4% of inpatients.

Adverse Events: Grade ≥ 3 infections occurred in 3 HaH patients (12%, all bacterial) versus 36 inpatients (20.5%; p&lt;0.05; 25 bacterial, 11 viral). Demographic factors, prior MM treatment, and clinical biomarkers did not influence infection occurrence. Amoxicillin prophylaxis was more common in the HaH cohort than in the inpatient cohort (58% vs. 28%; p&lt;0.05). TMP-SMX and antiviral prophylaxis rates were similar between cohorts (p=not significant [NS]). Immunoglobulin supplementation was also comparable (60% in HaH and 55.7% in inpatients). There was no significant difference in grade ≥ 3 cytopenias between the cohorts. Baseline neutropenia (HR 2.84; 95% CI, 1.59-5.09), monoclonal protein level (HR 1.76; 95% CI, 1.13-2.74), and hypoalbuminemia (HR 1.59; 95% CI, 1.01-2.20) were associated with higher cytopenia risk, while age over 75 years was associated with a reduced cytopenia risk (HR 0.35; 95% CI, 0.21-0.57). Overall, there was no significant difference in grade ≥ 3 adverse events between the cohorts.

Efficacy and Prognostic Factors: Overall survival (OS), progression-free survival (PFS), and time to treatment failure (TTF) were similar between HaH and inpatient cohorts (p=NS). Median PFS, OS, and TTF were not reached, with all HaH patients still alive. HaH did not significantly impact PFS (HR 1.76; 95% CI, 0.47-5.89). Performance status 2-4 (HR 2.86; 95% CI, 1.75-4.70) significantly increased progression risk, while age over 75 (HR 0.53; 95% CI, 0.3-0.93) was associated with a lower progression risk. HaH did not significantly affect TTF (HR 1.37; 95% CI, 0.39-4.85), whereas performance status 2-4 (HR 3.87; 95% CI, 2.39-6.27), renal insufficiency (HR 2.20; 95% CI, 1.27-3.83), increased LDH (HR 2.09; 95% CI, 1.25-3.48), monoclonal protein level (HR 2.08; 95% CI, 1.28-3.40), and hypoalbuminemia (HR 2.08; 95% CI, 1.28-3.40) were linked to shorter TTF. The HaH cohort had higher complete response rates (56% vs. 31.2%) and very good partial response rates (28% vs. 11.4%) compared to inpatients, with similar partial response rates (16% vs. 16.5%).

Conclusion: This study demonstrates that BsAb treatment in HaH is a safe and effective alternative for MM patients, associated with a lower risk of grade ≥ 3 infections.