Abstract
BACKGROUND:
Teclistamab is the first-in-class B cell maturation × cluster of differentiation 3 T cell bispecific antibody approved in the United States for relapsed or refractory multiple myeloma (MM). During the first year following US Food and Drug Administration approval, many institutions initiated teclistamab step-up dosing (SUD) in hospital settings.
OBJECTIVE:
To describe patient characteristics, length of hospital stay (LOS) during SUD, and real-world incidence and management of cytokine release syndrome (CRS) among patients with MM who initiated teclistamab in US hospital settings.
METHODS:
This retrospective observational study used the Premier Healthcare Database and included patients (≥18 years) with confirmed MM who received at least 1 teclistamab administration in a hospital setting between November 1, 2022, and September 21, 2023. We descriptively analyzed characteristics across all patients included as well as SUD patterns, LOS (defined as the time between admission to discharge), and CRS in those who completed SUD. CRS was identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and a symptom- and treatment-based algorithm (the Keating algorithm).
RESULTS:
A total of 413 patients were included. The median age (range) of the patients was 69 (32-89) years, 47.5% of patients were aged at least 70 years, and 69.7% had Medicare insurance. Most patients were male (56.4%), White (63.4%), and non-Hispanic (86.0%); 24.2% were Black. Most patients were treated in urban hospitals (96.4%), with 86.7% in teaching hospitals and 90.8% in hospitals with at least 300 beds. At the index hospital encounter, 47.9% of patients presented with anemia, 40.0% with peripheral neuropathy, and 35.8% with renal impairment/failure. Among 302 patients who completed SUD as of the data cutoff, 91.4% completed SUD in a single inpatient admission with a mean LOS of 8.7 days, after omitting extreme outliers; most patients had a 2-day (36.1%) or 3-day (31.1%) interval between SUD doses. CRS, per ICD-10-CM codes, was observed in 31.8% of patients (24.2% grade 1, 4.6% grade 2, and 1.0% grade 3). Per the Keating algorithm, 28.5% of patients experienced CRS-related symptoms, including fever (15.2%) and hypotension (10.3%); most of the events were classified as mild. Most patients with a complete SUD period had documented dexamethasone (97.0%) and acetaminophen (93.7%), 78.5% received diphenhydramine, and 29.8% received tocilizumab at any time during the SUD period.
CONCLUSIONS:
This large, national, real-world study of patients with MM treated with teclistamab confirmed that early initiators of teclistamab were older adults from diverse racial groups with substantial comorbidities. Despite these factors, most patients were able to safely complete SUD following label-described schedules with manageable CRS events.
Plain language summary
This study evaluated characteristics of real-world patients who received teclistamab in US hospitals to treat multiple myeloma (MM). This study also examined the teclistamab step-up dosing (SUD) process. We observed that early users of teclistamab were older adults from diverse racial groups who had multiple significant medical conditions. Despite these factors, most patients completed teclistamab step-up doses following label-suggested schedules without delay. Cytokine release syndrome was generally manageable and mostly low grade.
Implications for managed care pharmacy
This study confirms that most patients with MM can complete teclistamab SUD following label-described schedules without interruptions or delays and that the adverse event profile during the SUD period is predictable and can be effectively managed with supportive treatment. The findings of this study can help optimize resource allocation, inform the care model evolvement, and improve patient experience related to teclistamab SUD.
Multiple myeloma (MM), a plasma cell malignancy characterized by increased proliferation of monoclonal immuno-globulins, is the second most common hematologic cancer in the United States with an estimated 35,780 new cases in 2024. 1 The survival of patients with MM has markedly improved in the last decade with the introduction of novel targeted therapies including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. 2 – 4 Despite advances in treatment, MM remains incurable, as most patients with MM experience disease relapse or become refractory to available therapies and require additional rounds of treatment. 4 – 6 Novel therapeutic agents are critically needed for patients with relapsed or refractory MM (RRMM) owing to associated poor prognosis and limited treatment options. 7 , 8
Teclistamab was the first-in-class B cell maturation antigen–directed cluster of differentiation 3 T cell–engaging bispecific antibody to gain US regulatory approval in October 2022 for the treatment of adult patients with RRMM who have received at least 4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti–cluster of differentiation 38 monoclonal antibody (defined as triple-class exposed). 9 In the long-term follow-up analysis of the pivotal MajesTEC-1 trial, 10 participants who received teclistamab achieved an overall response rate of 63.0% and a median duration of response of 24.0 months (95% CI = 17.0 to not estimable) at the 30.4-month follow-up. 11 Cytokine release syndrome (CRS) occurred in 72.1% of participants receiving teclistamab in MajesTEC-1, with most events being grade 1 or 2 in severity and 1 event being grade 3 (0.6%); no patients discontinued teclistamab because of CRS. 10 Most of these participants experienced CRS during the step-up dosing (SUD) period, which consists of 2 step-up doses (0.06 mg/kg and 0.3 mg/kg) and the first full dose (1.5 mg/kg). 10
As with many other pivotal clinical trials, MajesTEC-1 had strict inclusion and exclusion criteria. As such, trial participants may not represent all indicated real-world patients with RRMM treated with teclistamab. Before receiving teclistamab, many patients indicated for teclistamab are likely refractory to existing targeted treatment options and/or are unable to receive chimeric antigen receptor T cell therapy for logistic or clinical reasons. Compared with those of MajesTEC-1 participants, the results of real-world analyses suggest that early initiators of teclistamab in the real world tend to be older, have poor Eastern Cooperative Oncology Group performance status, and have more extramedullary disease and substantial comorbidities, such as renal impairment. 12 – 17
Following US Food and Drug Administration (FDA) approval of teclistamab, many institutions initially administered teclistamab step-up doses in hospital settings to ensure patient safety. 18 However, there is a growing interest in shifting teclistamab SUD administration from inpatient to outpatient settings to enhance patient convenience and reduce health care resource utilization. 19 As health care centers gain more experience with teclistamab, both SUD administration and patient care models are evolving, driven by real-world evidence to continually improve teclistamab administration processes and patient outcomes. In a recent systematic literature review evaluating real-world evidence in patients with MM, Derman et al reported that some institutions have begun implementing outpatient SUD models. 20
In this study, we aimed to use a nationally representative, hospital-focused database to describe patient demographic and clinical characteristics, length of hospital stays (LOSs) during the SUD period, and real-world incidence and management of CRS among patients with MM who initiated teclistamab in US hospital settings during the first year after FDA approval of teclistamab. Detailed real-world evidence from this study regarding teclistamab SUD will help improve patient care models.
Methods
STUDY DESIGN AND DATA SOURCE
In this retrospective, observational cohort study, we used the Premier Healthcare Database, an all-payer US hospital administrative database, to identify patients with at least 1 hospital encounter containing teclistamab administration between November 1, 2022, and September 21, 2023. The Premier Healthcare Database contains inpatient and outpatient visits primarily from geographically diverse nonprofit, nongovernmental, community, and teaching (approximately 31%) and nonteaching (approximately 69%) hospitals and health systems. 21 The database contains data from more than 1 billion patient encounters, which equates to approximately 1 in 5 inpatient hospital stays in the United States. The database contains comprehensive patient and provider demographics and claims-level patient information, such as diagnoses, procedures, discharge, and detailed billing information from more than 600 acute care hospitals across all US regions, allowing evaluation of a large, diverse patient population across the country. It includes only de-identified patient data and is fully compliant with the Health Insurance Portability and Accountability Act. This study was reviewed by the New England Institutional Review Board (IRB), was determined not to constitute research involving human subjects, and was, therefore, exempt from IRB approval.
STUDY POPULATION AND COHORT IDENTIFICATION
This study included adult patients (aged ≥18 years) with confirmed MM (≥1 MM diagnosis based on the International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code C90.0x). Eligible patients had hospital encounters (including inpatient admissions and outpatient encounters) containing at least 1 teclistamab administration recorded at a US hospital within the Premier Healthcare Network between November 1, 2022, and September 21, 2023 (data cutoff date). Teclistamab records in the database were identified using the ICD-10 Procedure Coding System (PCS) code XW01348, the Healthcare Common PCS (HCPCS) code C9148, and a search for drug name “teclistamab.” The date of the earliest hospital encounter during which a teclistamab 30-mg/3-mL vial was administered was defined as the index date. Patients enrolled in clinical trials (based on ICD-10-PCS code Z00.6 and HCPCS codes S9988, S9990, S9991, S9992, S9994, or S9996 on or after the index date) were excluded.
Patients were considered as having a complete SUD schedule (defined as having received the 2 step-up doses of 0.06 mg and 0.3 mg per kilogram of body weight and the first full treatment dose of 1.5 mg per kilogram) if they met the following criteria. Teclistamab usage was identified in the database using procedure codes and standard charge description field. We validated the accuracy and completeness of SUDs using an algorithm based on the observed vials administered and the time of administration. The algorithm required an initial vial size of 30 mg/3 mL as the initial step-up dose for the patient, and a subsequent 153-mg/1.7-mL vial was the last dose of the step-up dose period.
STUDY MEASURES AND DATA ANALYSIS
Baseline patient demographic and clinical characteristics including comorbidities were assessed at the index date. LOS (defined as the time between admission to discharge) and CRS incidence and management were assessed between the index date and the end of the SUD period. Medications administered during the SUD period were assessed overall, as well as at least 1 day prior, on the same day, and at least 1 day after teclistamab step-up doses. All variables were analyzed descriptively. Mean (SD) and median (range or quartile 1 [Q1]-Q3) were reported for continuous variables, and numbers and percentages were reported for categorical variables. Characteristics of patients and treating hospitals were analyzed across all patients included in this study to provide a comprehensive overview of real-world patients who received teclistamab, regardless of whether they completed the SUD period or not. Health care resource utilization and CRS-related outcomes during SUD were evaluated only in patients with a complete SUD period. In an attempt to address potential underreporting of CRS in secondary data, we identified CRS using 2 methods: (1) ICD-10-CM codes and (2) an algorithm of CRS-related symptom and treatment codes published by Keating et al (the Keating algorithm). 22 All statistical analyses were conducted using SAS software, version 9.4 (SAS Institute Inc.).
Results
PATIENT CHARACTERISTICS
A total of 413 patients were included in this study (Supplementary Figure 1 (214.6KB, pdf) , available in online article). The median age (range) of the patients was 69 (32-89) years with 47.5% of patients aged at least 70 years (Table 1). More than half (56.4%) of the patients were male. Most patients were non-Hispanic (86.0%) and White (63.4%). Black or African American patients accounted for 24.2% of the total number of patients. Most of the overall patients (69.7%) had a Medicare plan.
TABLE 1.
Characteristics of Real-World Patients With Multiple Myeloma Treated With Teclistamab in a Hospital Setting
| All patients (N = 413) | Patients with complete SUD (n = 302) | |
|---|---|---|
| Patient demographics | ||
| Age, y | ||
| Mean (SD) | 67.4 (10.3) | 67.6 (10.5) |
| Median (range) | 69 (32-89) | 70 (32-89) |
| Age categories, n (%) | ||
| <65 y | 158 (38.3) | 112 (37.1) |
| 65 to <70 y | 59 (14.3) | 37 (12.3) |
| 70 to <75 y | 82 (19.9) | 64 (21.2) |
| ≥75 y | 114 (27.6) | 89 (29.5) |
| Sex, n (%) | ||
| Male | 233 (56.4) | 162 (53.6) |
| Female | 180 (43.6) | 140 (46.4) |
| Race, n (%) | ||
| White | 262 (63.4) | 183 (60.6) |
| Black or African American | 100 (24.2) | 74 (24.5) |
| Asian | 15 (3.6) | 12 (4.0) |
| Other | 33 (8.0) | 30 (9.9) |
| Unknown | 3 (< 1) | 3 (1.0) |
| Ethnicity, n (%) | ||
| Hispanic | 41 (9.9) | 34 (11.3) |
| Non-Hispanic | 355 (86.0) | 258 (85.4) |
| Unknown | 17 (4.1) | 10 (3.3) |
| Marital status, n (%) | ||
| Married | 260 (63.0) | 195 (64.6) |
| Single | 143 (34.6) | 98 (32.5) |
| Other | 6 (1.5) | 5 (1.7) |
| Unknown | 4 (1.0) | 4 (1.3) |
| Payer type, n (%) | ||
| Medicare | 288 (69.7) | 210 (69.5) |
| Medicaid | 36 (8.7) | 32 (10.6) |
| Commercial | 19 (4.6) | 9 (3.0) |
| Managed care | 51 (12.4) | 39 (12.9) |
| Other | 19 (4.6) | 12 (4.0) |
| Patient clinical characteristics | ||
| QCCI score, mean (SD) | 1.3 (1.7) | 1.4 (1.8) |
| QCCI categories, n (%) | ||
| 0 | 191 (46.2) | 123 (40.7) |
| 1 | 74 (17.9) | 62 (20.5) |
| 2 | 73 (17.7) | 56 (18.5) |
| ≥3 | 75 (18.2) | 61 (20.2) |
| Severity of illness a | ||
| Extreme | 60 (14.5) | 46 (15.2) |
| Major | 193 (46.7) | 168 (55.6) |
| Moderate | 83 (20.1) | 71 (23.5) |
| Minor | 4 (1.0) | 2 (<1) |
| Unknown | 73 (17.7) | 15 (5.0) |
| Risk of mortality a | ||
| Extreme | 22 (5.3) | 11 (3.6) |
| Major | 111 (26.9) | 102 (33.8) |
| Moderate | 206 (49.9) | 173 (57.3) |
| Minor | 1 (< 1) | 1 (<1) |
| Unknown | 73 (17.7) | 15 (5.0) |
| Select documented conditions at index hospital encounter, n (%) | ||
| Hypertension | 244 (59.1) | 199 (65.9) |
| Anemia | 198 (47.9) | 161 (53.3) |
| Peripheral neuropathy | 165 (40.0) | 131 (43.4) |
| Renal impairment/failure | 148 (35.8) | 119 (39.4) |
| Osteoporosis | 142 (34.4) | 117 (38.7) |
| Headaches/migraines | 95 (23.0) | 82 (27.2) |
| Congestive heart failure | 69 (16.7) | 58 (19.2) |
| Chronic pulmonary disease | 44 (10.6) | 41 (13.6) |
| Neutropenia | 40 (9.7) | 29 (9.6) |
| Hypogammaglobulinemia | 40 (9.7) | 28 (9.3) |
| Hypercalcemia | 37 (9.0) | 31 (10.3) |
Severity of illness and risk of mortality was evaluated based on the All Patient Refined Diagnosis Related Group classification system.
QCCI = Quan-Charlson comorbidity index; SUD = step-up dosing; y = years.
At the index hospital encounter, 61.2% of patients had a major or extreme illness and 32.2% had a major or extreme risk of mortality based on the All Patient Refined Diagnosis Related Group (DRG) classification system, 23 which expands the basic DRG structure by including 4 subclasses to each DRG and is a variable unique to the Premier Healthcare database. A total of 47.9% presented with anemia, 40.0% with peripheral neuropathy, 35.8% with renal impairment/failure, 9.7% with neutropenia, 9.7% with hypogammaglobulinemia, and 9.0% with hypercalcemia (Table 1).
TECLISTAMAB SUD SETTING AND SCHEDULE
Most patients (96.4%) received teclistamab in urban hospitals (Table 2), with 86.7% in teaching hospitals and 90.8% in hospitals with at least 300 beds. More hospitals in the South (40.4%) were represented in this study compared with hospitals in the Northeast (23.7%), Midwest (23.5%), and West (12.4%). This distribution is consistent with that of the Premier Healthcare Database.
TABLE 2.
Characteristics of Hospital Encounters Containing At Least 1 Teclistamab Administration
| All patients (N = 413), n (%) | Patients with complete SUD (n = 302), n (%) | |
|---|---|---|
| Hospital status | ||
| Teaching | 358 (86.7) | 276 (91.4) |
| Nonteaching | 55 (13.3) | 26 (8.6) |
| Urbanicity | ||
| Urban | 398 (96.4) | 295 (97.7) |
| Rural | 15 (3.6) | 7 (2.3) |
| Hospital region | ||
| Northeast | 98 (23.7) | 87 (28.8) |
| Midwest | 97 (23.5) | 77 (25.5) |
| South | 167 (40.4) | 111 (36.8) |
| West | 51 (12.4) | 27 (8.9) |
| Size (number of beds) | ||
| 0-99 | 11 (2.7) | 4 (1.3) |
| 100-199 | 22 (5.3) | 11 (3.6) |
| 200-299 | 5 (1.2) | 3 (<1) |
| ≥300 | 375 (90.8) | 284 (94.0) |
SUD = step-up dosing.
Among 302 patients with a complete SUD period at data cutoff, 276 (91.4%) received the entire SUD in a single inpatient admission, 14 (4.6%) in outpatient settings, and 3 (<1%) in a combination of inpatient and outpatient settings (Table 3). The median (Q1-Q3) LOS among all patients with a complete SUD period was 8 (7-10) days, with a mean (SD) of 8.7 (3.3) days when excluding 95th percentile outliers. Of the 276 patients who completed teclistamab SUD in 1 inpatient admission, 243 (88.0%) received teclistamab on the first day of their hospital admission, whereas 44 (15.9%) received teclistamab on the second day or later of their hospital admission. The median (Q1-Q3) LOS for patients who started teclistamab on the first day of inpatient admission was shorter than for patients who started teclistamab on the second day or later (8 [6-9] days vs 17 [12-28] days).
TABLE 3.
Real-World SUD Pattern Among Patients Who Completed SUD (n = 302)
| SUD patterns | |
|---|---|
| SUD completion pattern, n (%) | 302 (100.0) |
| 1 inpatient admission | 276 (91.4) |
| Multiple inpatient admissions | 9 (3.0) |
| Inpatient and outpatient admissions | 3 (<1.0) |
| Multiple outpatient admissions | 14 (4.6) |
| Patients starting teclistamab on day 1 of admission, n (%) | 243 (80.5) |
| Length of stay, mean (SD), days | 8.3 (3.4) |
| Length of stay, median (Q1-Q3), days | 8 (6-9) |
| Patients starting teclistamab on day ≥2 of admission, n (%) | 44 (14.6) |
| Length of stay, mean (SD), days | 20.6 (11.2) |
| Length of stay, median (Q1-Q3), days | 17 (12-28) |
| Length of stay of all patients with a complete SUD period | |
| Mean (SD), days | 10.0 (6.8) |
| Median (Q1-Q3), days | 8 (7-10) |
| Length of stay (excluding the 95th percentile outliers) | |
| Mean (SD), days | 8.7 (3.3) |
| Median (Q1-Q3), days | 8 (6-9) |
| SUD schedule pattern, n (%) | |
| 3-day interval | 94 (31.1) |
| 2-day interval | 109 (36.1) |
| Other | 99 (32.8) |
Q = quartile; SUD = step-up dosing.
REAL-WORLD INCIDENCE AND SEVERITY OF CRS
Of the 302 patients with a complete SUD period by data cutoff, 96 (31.8%) experienced CRS per ICD-10-CM diagnostic codes (CRS: D89.831-D89.839, grade 1: D89.831, grade 2: D89.832, grade 3: D89.833. grade 4: D89.834, grade 5: D89.835, and grade unspecified: D89.839). A total of 73 patients (24.2%) had grade 1 events, 14 patients (4.6%) had grade 2 events, and 3 patients (1.0%) had grade 3 events; no patient had grade 4 or above CRS events (Table 4). Per the symptom-based Keating classification (Supplementary Table 1 (214.6KB, pdf) ), 86 patients (28.5%) experienced CRS-related symptoms, including fever (15.2%), hypotension (10.3%), fatigue (3.6%), hypoxia (2.3%), and headaches (2.0%); most of these events (80 of 86) were mild (Table 4).
TABLE 4.
Incidence and Severity of CRS During Teclistamab Step-Up Dosing Among Patients Who Completed Step-Up Dosing (n = 302)
| Incidence and severity | |
|---|---|
| Patients with ≥1 CRS events per ICD-10-CM codes, n (%) | 96 (31.8) |
| Grade 1 | 73 (24.2) |
| Grade 2 | 14 (4.6) |
| Grade 3 | 3 (1.0) |
| Grade 4 or 5 | 0 |
| Grade unknown or unspecified | 6 (2.0) |
| Patients with ≥1 CRS events per symptom-based Keating algorithm, n (%) | |
| Fever | 46 (15.2) |
| Hypotension | 31 (10.3) |
| Fatigue | 11 (3.6) |
| Hypoxia | 7 (2.3) |
| Headaches | 6 (2.0) |
| Patients with CRS events per Keating classifications, n (%) | |
| Any grade CRS (loose definition) | 86 (28.5) |
| Mild | 80 (26.5) |
| Severe | 6 (2.0) |
| None | 216 (71.5) |
CRS = cytokine release syndrome; ICD-10-CM = International Classification of Diseases, Tenth Revision, Clinical Modification.
ADVERSE EVENT MANAGEMENT DURING SUD
Most patients who completed the SUD period had documented receipt of dexamethasone (97.0%) and acetaminophen (93.7%), 78.5% received diphenhydramine, and 29.8% received tocilizumab at any time during the SUD period. Of the 90 patients treated with tocilizumab during the SUD period, 58 (64.4%) also had an ICD-10-CM code for a CRS event, including 44 (48.9%) grade 1, 10 (11.1%) grade 2, and 4 (4.4%) unknown or unspecified grade events (Supplementary Table 2 (214.6KB, pdf) ). A total of 21 patients (7.0%) also received positive pressure support, including supplemental oxygen (5.3%), bilevel positive airway pressure or continuous positive airway pressure (3.0%), invasive mechanical ventilation (1.7%), intubation (1.7%), and other unspecified hypoxia-related management (5.3%). Forty-five patients (14.9%) underwent a chest X-ray, 8 patients (2.7%) had a chest or abdominal computed tomography scan, and 3 patients (1.0%) received a brain magnetic resonance imaging scan. Although most patients received dexamethasone, acetaminophen, and diphenhydramine on the same day as their teclistamab step-up doses, tocilizumab was given primarily at least 1 day after (Figure 1).
FIGURE 1.
Medication Use for Adverse Event Management During Step-Up Dosing
Step-up dose 1 = 0.06 mg/kg of body weight, step-up dose 2 = 0.3 mg/kg of body weight, and full treatment dose = 1.5 mg/kg of body weight.
Discussion
To our knowledge, this is the largest real-world study evaluating patients with MM who received commercial teclistamab in multiple hospital settings across the United States within the first year of market availability. This study assessed the patient profile, SUD process, and early safety outcomes of teclistamab. Consistent with real-world evidence generated from other data sources, 17 , 24 , 25 this study found that real-world patients treated with teclistamab were older adults with substantial comorbidities, including some (eg, renal disease and neutropenia) that may have been deemed ineligible for the MajesTEC-1 clinical trial. Additionally, compared with participants in MajesTEC-1, the median age of the real-world patients was numerically higher (69 vs 64 years), and a higher proportion of the real-world patients were Black (24.2% vs 12.7%). Despite the advanced age and a more diverse population in the real world, most patients in this study completed SUD without delay, following a 2- or 3-day dosing interval. This finding is consistent with results of other real-world analyses using the All-payer Real-world MM Research-ready Data registry and Acentrus MM electronic medical records, respectively, which showed that most real-world patients were able to complete SUD as planned and that the duration of the SUD period decreased over time. 25 , 26
In this study, we also found that most patients received teclistamab step-up doses in large (≥300 beds) teaching hospitals in urban areas. This pattern may partly reflect the characteristics of the Premier Healthcare Database, which includes data primarily from urban hospitals. However, the proportions of urban (96.4%), large (90.8%), and teaching (86.7%) hospitals in this study are notably higher than the overall composition of hospitals in the database (approximately 70% urban, 30% with ≥300 beds, and 31% teaching). 27 These findings suggest that the early adoption of innovative therapies, such as teclistamab, is more prevalent in large, academic, research centers, which generally have more resources and prior clinical trial experience than smaller, nonacademic institutions.
As expected of early initiators of teclistamab, most patients in this study completed SUD in a single inpatient admission, with most initiating teclistamab on the first day of their hospital admission. We observed that patients who started teclistamab on the second day or later had longer median LOS compared with those who started teclistamab on the first day and that some patients who initiated teclistamab late in their hospital stay were initially admitted for reasons unrelated to teclistamab administration. This suggests that some patients may have already been quite ill before starting teclistamab, which may have caused delays in initiating treatment.
Given that this study used a hospital-focused database, it is likely that most patients included in this study were those who initiated teclistamab SUD in inpatient settings. Nonetheless, it is worth noting that 14 patients in this study completed their SUD entirely in a hospital-based outpatient setting as of the September 21, 2023, data cutoff date. This finding is consistent with real-world studies demonstrating that teclistamab SUD can be safely initiated and completed in outpatient settings. 24 , 28 , 29 In a recent study of real-world safety outcomes of teclistamab under an outpatient model for SUD administration, Sandahl et al reported teclistamab outpatient administration as a safe and feasible option for select patients. 24 In the TecPIONEER study by Derman et al, which involved a group of hematologists who were early adopters of teclistamab, 26% reported administering teclistamab SUD in an outpatient or hybrid setting, and all expressed interest in developing the necessary infrastructure to administer teclistamab SUD in the outpatient setting within their institutions. 19 As health care centers and community-based hospitals across the country gain more experience with teclistamab administration, we anticipate that more patients will initiate teclistamab directly in outpatient settings.
Consistent with the MajesTEC-1 trial and other real-world studies of teclistamab, 10 , 12 , 14 , 15 , 20 most of the CRS events identified in this study were low grade in severity. Numerically, the real-world CRS rates observed in this study were substantially lower than what was observed in the MajesTEC-1 trial (31.8% by ICD-10-CM codes and 28.5% by the Keating algorithm vs 72.1%) despite the real-world patients being older and having substantial comorbidities. The CRS rates in our study are consistent with other real-world studies evaluating safety outcomes of teclistamab using secondary data but lower than retro-spective chart review studies. 12 – 16 , 25 , 26 Given that the CRS events in this study were captured based on either the ICD-10-CM diagnosis codes or the Keating algorithm, which is based on symptoms captured by health care providers, it is likely that the CRS events were underreported in secondary data. It is also possible that the lower CRS rates captured in this study and other real-world studies are associated with differences in CRS event monitoring and reporting criteria relative to those used in the MajesTEC-1 trial. As highlighted in the systematic review by Derman et al, real-world studies have reported varying but consistently lower CRS rates, ranging from 18% to 65%, compared with the MajesTEC-1 trial. 10 , 12 , 16 , 20 , 25
This study also revealed that most real-world patients received corticosteroids, diphenhydramine, and acetaminophen on the same day as their teclistamab step-up doses. It is likely that these medications were given based on the recommendations in the teclistamab label. Conversely, tocilizumab was given primarily at least 1 day after the teclistamab step-up doses rather than on the same day, suggesting that it was likely used as treatment or secondary prophylaxis.
LIMITATIONS
This study has limitations inherent to observational studies with data from claims databases. Most importantly, it relied on hospital administrative discharge data. As a result, it is subject to secondary database limitations, including coding errors, misclassification, incomplete patient information, and an inability to accurately determine patients’ comorbidities, MM-related conditions and clinical characteristics, and full treatment history. Addi-tionally, the database does not contain continuous enrollment information, and when discharged patients visit an out-of-network hospital or ambulatory centers, their information might not be fully captured. Consequently, comorbidities are likely underreported. Lastly, most patients in this study received teclistamab at large teaching hospitals that are part of the Premier Healthcare Network; therefore, the results of this study may not be generalizable to patients with MM who received teclistamab elsewhere. We also note that the teclistamab administration model and adverse event management may change in the future as treatment guidelines evolve. Despite these limitations, in this, the only real-world analysis known to date that uses US national hospital chargemaster data to assess patients with MM who received commercial teclistamab, we found that real-world patients were able to safely complete SUD as planned, with relatively low CRS rates and a manageable CRS profile.
Conclusions
This is the largest real-world study of patients with MM treated with teclistamab using a nationally representative all-payer US hospital-based database. Real-world early initiators of teclistamab were older adults from diverse racial groups who had substantial comorbidities. Despite these factors, most patients were able to complete SUD as scheduled without delay. The real-world CRS rate during SUD observed in this study was lower than the MajesTEC-1 trial, with most of the events being of low-grade severity. Future studies will examine the evolving patient profiles and teclistamab care models, long-term treatment patterns, and effectiveness and safety outcomes of teclistamab in patients with MM.
DISCLOSURES
This study was funded by Janssen Scientific Affairs, LLC, located in Horsham, PA. The contents of this publication are solely the responsibility of the authors.
ACKNOWLEDGMENTS
The authors would like to acknowledge Lee A. Zarzabal of Simulstat Inc. for providing programming support and Dr Yanni Wang and Dr Hongping Tian of Cobbs Creek Healthcare LLC for medical writing and editing assistance.
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