A Comprehensive Clinical and Pharmacological Review of Teclistamab (Tecvayli): A First-in-Class BCMAxCD3 Bispecific Antibody for Relapsed/Refractory Multiple Myeloma

Section 1: Introduction and Drug Profile

1.1. Overview

Teclistamab, marketed under the brand name Tecvayli, represents a significant milestone in the treatment of multiple myeloma, a hematologic malignancy characterized by the proliferation of cancerous plasma cells.[1] It is a first-in-class, off-the-shelf bispecific T-cell engager (BiTE) antibody developed by Janssen Pharmaceuticals.[2] The therapy is specifically designed to address the profound unmet medical need for patients with relapsed and refractory multiple myeloma (RRMM) who have exhausted multiple prior lines of standard therapy, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies.[1]

The development and approval of Teclistamab herald a new era of immunotherapy for this incurable disease. Its novel mechanism of action, which leverages the patient's own immune system to target and eliminate malignant cells, has demonstrated impressive rates of deep and durable responses in a heavily pretreated population with a historically poor prognosis.[1] In recognition of its potential to substantially improve upon available therapies, Teclistamab received accelerated and conditional marketing authorizations from major global regulatory bodies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).[2] This report provides an exhaustive clinical and pharmacological review of Teclistamab, detailing its mechanism, the pivotal clinical evidence supporting its use, its comprehensive safety profile, and its strategic position within the evolving therapeutic landscape of multiple myeloma.

1.2. Identification and Physicochemical Properties

Teclistamab is a complex biotechnology product with specific identifiers and properties that are crucial for its precise characterization. It is a humanized monoclonal antibody of the Immunoglobulin G4 (IgG4) subclass, engineered using recombinant DNA technology and produced in mammalian Chinese Hamster Ovary (CHO) cells.[2] In the United States, its nonproprietary name is teclistamab-cqyv; the "-cqyv" suffix is a four-letter, non-meaningful designation applied to distinguish it from other related biological products, as per FDA naming conventions.[2] Its fundamental properties are summarized in Table 1.

Table 1: Drug Identification and Key Properties

Property	Value	Source(s)
Generic Name	Teclistamab	2
Brand Name	Tecvayli (teclistamab-cqyv)	2
DrugBank ID	DB16655	2
Type	Biotech; Bispecific Monoclonal Antibody	2
CAS Number	2119595-80-9	2
Other Names/Codes	JNJ-64007957, teclistamabum	2
Chemical Formula	C6383​H9847​N1695​O2003​S40​	2
Molar Mass	Approx. 143,662.25 g·mol⁻¹ (146 kDa)	2
Source	Humanized, produced in CHO cells	2
Drug Class	Antineoplastic Agent; T-cell Engager	2
ATC Code	L01FX24	2

Section 2: Mechanism of Action and Clinical Pharmacology

2.1. Dual Targeting of BCMA and CD3: The Bispecific Bridge

The therapeutic activity of Teclistamab is rooted in its sophisticated bispecific design, which enables it to function as a potent T-cell engager.[2] The molecule is engineered with two distinct antigen-binding arms. One arm possesses high affinity for the B-cell maturation antigen (BCMA), also known as Tumor Necrosis Factor Receptor Superfamily Member 17 (TNFRSF17).[2] BCMA is a cell surface protein that is minimally expressed on normal cells but is highly and preferentially expressed on mature B-lineage cells, including the malignant plasma cells that characterize multiple myeloma.[13] In myeloma cells, BCMA signaling is crucial for promoting cell survival, proliferation, and maturation, making it an ideal therapeutic target.[13]

The second arm of the Teclistamab antibody is designed to bind specifically to the CD3 epsilon (CD3ϵ) chain, a key component of the T-cell receptor (TCR) complex found on the surface of all T-cells.[2] By simultaneously engaging both BCMA on a myeloma cell and CD3 on a T-cell, Teclistamab acts as a molecular bridge, physically linking the cytotoxic immune effector cell to the cancerous target cell.[4] This forced proximity creates a transient but highly effective immunological synapse, initiating a targeted cytotoxic response that circumvents the natural mechanisms of tumor immune evasion. The antibody's structure is based on a human IgG4-PAA (proline, alanine, alanine) format, which includes modifications to the hinge region to prevent Fc-mediated effector functions and improve stability, with two interchain disulfide bonds connecting the anti-BCMA and anti-CD3 components.[5]

2.2. T-Cell Activation and Induced Cytotoxicity

The formation of the Teclistamab-mediated immunological synapse is the critical initiating event for its antitumor activity. The binding and cross-linking of the CD3 receptor on the T-cell surface triggers a powerful activation signal, independent of the T-cell's natural antigen specificity.[5] This leads to the robust activation, proliferation, and differentiation of the engaged T-cells into cytotoxic T-lymphocytes (CTLs).[5]

Once activated, these CTLs unleash their cytotoxic payload directly onto the tethered myeloma cell. This process involves the release of proinflammatory cytokines, such as interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-gamma (IFN-γ), which further amplify the immune response.[13] Concurrently, the CTLs release cytolytic granules containing perforin and various granzymes. Perforin creates pores in the target cell's membrane, allowing granzymes to enter and initiate the caspase cascade, ultimately leading to apoptosis, or programmed cell death, of the BCMA-expressing myeloma cell.[13] This mechanism effectively redirects the patient's endogenous T-cell population to recognize and eliminate malignant plasma cells throughout the body.[5]

The dual-targeting mechanism is fundamental to understanding both the drug's efficacy and its primary toxicities. The very same process of potent, widespread T-cell activation that leads to the destruction of myeloma cells is also responsible for the systemic inflammatory response that manifests as Cytokine Release Syndrome (CRS) and the subsequent potential for neurologic toxicity. These adverse events are not off-target side effects in the traditional sense, but rather an on-target, mechanism-based consequence of the drug's intended pharmacological action. This direct linkage explains why the risk of these toxicities cannot be entirely eliminated but must be carefully managed through specific mitigation strategies, such as the mandatory step-up dosing schedule and the Risk Evaluation and Mitigation Strategy (REMS) program.

2.3. Pharmacokinetics (Absorption, Distribution, Metabolism, Elimination - ADME)

The pharmacokinetic profile of Teclistamab has been characterized in clinical studies, defining its movement and persistence within the body following administration.

• Absorption: Teclistamab is administered via subcutaneous (SC) injection. Following SC administration, it is absorbed into systemic circulation with a mean absolute bioavailability estimated to be between 69% and 72%.[13] The absorption is slow, with the median time to reach maximum serum concentration ( Tmax​) occurring at 139 hours (approximately 5.8 days) after the first treatment dose.[1]
• Distribution: After reaching systemic circulation, Teclistamab distributes throughout the body. Following the 13th weekly dose of 1.5 mg/kg, the mean distribution half-life (t1/2α​) was determined to be 5.7 days, with a standard deviation of 2.4 days.[1] A critical unanswered question regarding its distribution is its ability to penetrate the central nervous system; its capacity to cross the blood-brain barrier is currently unknown.[20] This knowledge gap is particularly relevant given the observed neurologic toxicities, including ICANS.
• Metabolism: As a large protein-based therapeutic, Teclistamab is not metabolized by the hepatic cytochrome P450 (CYP450) enzyme system, which is the primary pathway for small-molecule drugs.[1] Instead, it is expected to undergo catabolism through general, non-specific protein degradation pathways, where it is broken down into smaller peptides and individual amino acids that are then recycled by the body.[20]
• Elimination: The clearance of Teclistamab is complex, involving both time-independent (linear) and time-dependent (nonlinear) pathways.[13] The time-dependent clearance is likely related to target-mediated drug disposition, where binding to BCMA on myeloma cells contributes to its elimination. At steady state, achieved after approximately 12 weekly doses, the linear pathway is predominant. The geometric mean clearance ( CL) at the 13th weekly dose was 0.472 L/day.[13] Teclistamab exhibits a long terminal elimination half-life ( t1/2β​). After the 13th weekly dose of 1.5 mg/kg, the mean elimination half-life was 27.2 days, with a standard deviation of 8.2 days.[1] This long half-life supports the weekly and subsequent biweekly maintenance dosing schedules. Due to this long half-life, a 4- to 5-fold accumulation in drug exposure is observed between the first and 13th weekly doses.[1]

The pharmacokinetic properties of Teclistamab, particularly its long half-life and "off-the-shelf" availability, present a distinct profile compared to autologous CAR T-cell therapies. While CAR-T cells are a "living drug" with cellular persistence but no circulating pharmacological agent, Teclistamab provides predictable pharmacokinetics and immediate availability. This is a significant logistical advantage, avoiding the multi-week manufacturing delays associated with CAR-T.[16] However, the long half-life also means that in the event of severe or prolonged toxicity, the instigating drug cannot be rapidly cleared from the patient's system. This poses a distinct clinical management challenge, as clinicians must treat the symptoms while the drug is slowly eliminated over several weeks, a contrast to managing CAR-T toxicities where the focus is on controlling the cellular response itself.

2.4. Pharmacodynamics and Drug Interactions

The pharmacodynamic effects of Teclistamab are a direct reflection of its mechanism of action and are critical biomarkers of its activity.

• Pharmacodynamic Effects: Upon administration, Teclistamab induces a cascade of measurable biological changes. These include the intended T-cell activation and redistribution, a marked reduction in circulating B-cells, and a transient but significant increase in serum concentrations of proinflammatory cytokines, including IL-6, IL-10, and the soluble IL-2 receptor (sIL-2R).[13] A key pharmacodynamic marker of antitumor activity is the level of soluble BCMA (sBCMA) in the serum. sBCMA is shed from the surface of myeloma cells and its levels often correlate with tumor burden and poor prognosis. Treatment with Teclistamab leads to a rapid and substantial reduction in sBCMA levels in the majority of patients, typically observed within the first month of therapy, providing an early indicator of target engagement and clinical activity.[13]
• Drug-Drug Interactions: Teclistamab has no direct pharmacokinetic interactions mediated by the CYP450 system. However, a clinically significant indirect interaction exists. The release of cytokines (particularly IL-6) induced by Teclistamab can transiently suppress the activity of various CYP450 enzymes.[22] This can lead to decreased metabolism and consequently increased plasma concentrations of co-administered drugs that are substrates for these enzymes. This is particularly concerning for drugs with a narrow therapeutic index, such as certain anticonvulsants (e.g., carbamazepine), immunosuppressants (e.g., cyclosporine), and opioids (e.g., alfentanil).[22] Therefore, patients receiving Teclistamab concurrently with sensitive CYP substrates require careful monitoring for signs of increased exposure or toxicity, and dose adjustments of the concomitant medication may be necessary, especially during the initial step-up dosing phase when cytokine release is most pronounced.

Section 3: Pivotal Clinical Evidence: The MajesTEC-1 Trial

3.1. Study Design and Patient Population

The regulatory approvals for Teclistamab were primarily based on the compelling results from the MajesTEC-1 study (registered under ClinicalTrials.gov identifiers NCT03145181 and NCT04557098).[3] This was a Phase 1/2, single-arm, open-label, multicohort, multicenter study designed to evaluate the safety, tolerability, and efficacy of Teclistamab in patients with RRMM.

• Study Design: The trial was structured in multiple parts. The initial Phase 1 portion (dose escalation and expansion) was designed to determine the safety profile and identify the recommended Phase 2 dose (RP2D).[23] The RP2D was established as a weekly subcutaneous injection of 1.5 mg/kg, following two smaller, weight-based step-up doses (0.06 mg/kg and 0.3 mg/kg) designed to mitigate the risk of CRS.[7] The subsequent Phase 2 portion of the study was designed to evaluate the efficacy of Teclistamab at this RP2D, with the primary endpoint being the overall response rate (ORR).[7]
• Patient Population: The study enrolled an exceptionally challenging patient population, reflective of the real-world unmet need in advanced multiple myeloma. Key eligibility criteria required adult patients to have a documented diagnosis of RRMM and to have received at least three prior lines of therapy, including mandatory exposure to a PI, an IMiD, and an anti-CD38 monoclonal antibody.[7] This defined the population as "triple-class exposed." Patients with prior exposure to a BCMA-targeted therapy were excluded from the main efficacy cohorts (A and B) but could be enrolled in a separate exploratory cohort (Cohort C) to assess activity in this emerging setting.[27]

The baseline characteristics of the 165 patients who received the RP2D and formed the pivotal efficacy and safety population underscore the advanced nature of their disease. These patients were heavily pretreated and had highly refractory myeloma, a context that is essential for interpreting the subsequent efficacy results. A summary of the trial design and key baseline patient characteristics is provided in Table 2.

Table 2: Summary of MajesTEC-1 Trial Design and Baseline Patient Characteristics (N=165)

Characteristic	Value	Source(s)
Trial Phase	Phase 1/2, Open-Label, Single-Arm	7
Primary Endpoint	Overall Response Rate (ORR)	7
Key Eligibility	Adults with RRMM; ≥3 prior lines of therapy (incl. PI, IMiD, anti-CD38 mAb)	7
Median Age (range)	64 years (33-84)	23
Sex (Male)	58.2%	23
Race (White)	81.2%	23
ISS Stage at Baseline	I: 52.5%, II: 35.2%, III: 12.3%	23
High-Risk Cytogenetics	25.9%	23
Extramedullary Plasmacytomas	17.0%	23
Median Prior Lines of Therapy (range)	5 (2-14)	7
Triple-Class Refractory	77.6%	7
Penta-Drug Refractory	30.3%	23

3.2. Efficacy and Clinical Response

In the context of this heavily pretreated and highly refractory patient population, Teclistamab demonstrated unprecedented efficacy, achieving high rates of deep and durable responses. The results from the MajesTEC-1 trial represent a significant improvement over historical outcomes for this patient group, where response rates to subsequent therapies are typically in the 25-30% range with short durations of disease control.[21]

• Overall Response Rate (ORR): In the primary efficacy analysis of 165 patients, with a median follow-up of 14.1 months, the Independent Review Committee-assessed ORR was 63.0% (95% Confidence Interval [CI], 55.2%-70.4%).[7] This high response rate was achieved rapidly, with the median time to first response being only 1.2 months (range, 0.2-5.5 months).[23]
• Depth of Response: The responses induced by Teclistamab were not only frequent but also remarkably deep. Of the 165 patients, 97 (58.8%) achieved a very good partial response (VGPR) or better, and 65 (39.4%) achieved a complete response (CR) or better.[7] With longer-term follow-up of 30.4 months, the responses continued to deepen, with the CR or better rate increasing to 46%.[25]
• Duration of Response (DOR): Crucially, these deep responses were also durable. The median DOR was 18.4 months (95% CI, 14.9 to not estimable), indicating sustained disease control for a clinically meaningful period.[7] For the cohort of patients who achieved a CR or better, the median DOR was not yet reached at the time of longer-term analysis, suggesting the potential for very long-lasting remissions in the best responders.[25]
• Progression-Free and Overall Survival (PFS/OS): The survival outcomes also reflected a substantial clinical benefit. The median PFS, the time patients lived without their cancer progressing, was 11.3 months (95% CI, 8.8 to 17.1 months).[7] The median OS was 18.3 months (95% CI, 15.1 to not estimable).[7]

The profound clinical benefit demonstrated in MajesTEC-1 provides the necessary justification for the drug's approval via expedited pathways. The greater than two-fold improvement in response rates and the significant extension in disease control and survival, when compared to the dismal outcomes historically seen in this patient population, create a highly favorable benefit-risk assessment. This assessment supports the use of the drug despite its significant toxicity profile, which is managed through the stringent REMS program and hospitalization requirements. The key efficacy results are summarized in Table 3.

Table 3: Key Efficacy Outcomes from MajesTEC-1 (RP2D Cohort, N=165)

Efficacy Endpoint	Result (Median Follow-up: 14.1 months)	Source(s)
Overall Response Rate (ORR)	63.0% (95% CI: 55.2–70.4)	7
Very Good Partial Response (VGPR) or Better	58.8%	7
Complete Response (CR) or Better	39.4%	7
Stringent Complete Response (sCR)	21.3%	23
Median Time to First Response	1.2 months (range: 0.2–5.5)	23
Median Duration of Response (DOR)	18.4 months (95% CI: 14.9–NE)	7
Median Progression-Free Survival (PFS)	11.3 months (95% CI: 8.8–17.1)	7
Median Overall Survival (OS)	18.3 months (95% CI: 15.1–NE)	7
NE = Not Estimable

3.3. Minimal Residual Disease (MRD) Negativity

Minimal residual disease (MRD) negativity is a measure of very deep response at the molecular level and is increasingly recognized as a powerful prognostic indicator in multiple myeloma. Teclistamab demonstrated the ability to induce high rates of MRD negativity. In the overall population of 165 patients, 44 (26.7%) achieved MRD negativity, as assessed by next-generation sequencing with a sensitivity threshold of one cancer cell per 100,000 cells (10−5).[7] This deep molecular clearance was particularly pronounced among the best responders; among the 65 patients who achieved a CR or better, the MRD negativity rate was 46%.[7] This finding further substantiates the profound depth of response achievable with Teclistamab therapy.

3.4. Subgroup Analysis: High-Risk and Post-BCMA Populations

The efficacy of Teclistamab was further explored in key patient subgroups to understand its activity in different clinical scenarios.

• High-Risk Patients: The drug maintained consistent activity in patients with traditionally poor-prognosis features. The ORR was similar to the overall population in subgroups with high-risk cytogenetics and in those who were penta-drug refractory.[23] However, response rates were observed to be lower in patients with a high burden of disease, such as those with extramedullary disease (EMD) or those with International Staging System (ISS) Stage III disease at baseline.[23]
• Prior BCMA Exposure (Cohort C): The activity of Teclistamab in patients who had already been treated with other BCMA-directed therapies is of critical clinical and strategic importance. In Cohort C of the MajesTEC-1 study, which enrolled 40 patients with prior exposure to BCMA-targeted agents (including antibody-drug conjugates and/or CAR T-cell therapies), Teclistamab still demonstrated substantial clinical benefit. The ORR in this highly refractory cohort was 52.5%.[27] This finding is supported by emerging real-world evidence, which has shown response rates of approximately 40% in patients treated with Teclistamab following progression on a BCMA-targeted ADC or CAR-T therapy.[32]

The demonstration of efficacy in patients who have already progressed on a BCMA-targeted therapy is a pivotal finding for the long-term strategic positioning of Teclistamab. As the therapeutic landscape becomes populated with multiple BCMA-directed agents, the question of how to sequence these therapies is paramount. This evidence suggests that resistance to one BCMA-targeting modality does not necessarily confer cross-resistance to all others. The mechanism of relapse after a prior BCMA therapy may be related to factors other than a complete loss of the BCMA target, such as T-cell fitness, changes in the tumor microenvironment, or differences in the specific BCMA epitope targeted by the different drugs. This positions Teclistamab not merely as a last-line option for BCMA-naïve patients, but as a viable and important sequencing option within the evolving paradigm of BCMA-directed immunotherapy, a crucial consideration for long-term treatment planning.

Section 4: Safety Profile and Management of Adverse Events

4.1. Overview of Adverse Reactions

The significant efficacy of Teclistamab is balanced by a notable and complex safety profile. The adverse events are largely predictable and directly related to the drug's mechanism of action. In the pivotal safety population of 165 patients from MajesTEC-1, serious adverse reactions occurred in 54% of patients, and fatal adverse reactions were reported in 5%.[8] The most common adverse reactions (occurring in ≥20% of patients) were pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea.[2] The most frequently observed Grade 3 to 4 laboratory abnormalities were hematologic, underscoring the drug's impact on bone marrow function.[2]

Table 4: Incidence of Common Adverse Reactions (≥20% Any Grade) in MajesTEC-1 (N=165)

Adverse Reaction	Any Grade (%)	Grade 3-4 (%)	Source(s)
Cytokine Release Syndrome (CRS)	72.1	0.6	7
Neutropenia	70.9	64.2	7
Anemia	52.1	37.0	7
Thrombocytopenia	40.0	21.2	7
Infections	76.4	44.8	7
Pyrexia (Fever)	38.8	2.4	2
Musculoskeletal Pain	33.3	3.0	2
Fatigue	27.9	3.0	2
Injection Site Reaction	26.1	0	2
Upper Respiratory Tract Infection	24.8	1.8	2
Nausea	22.4	0.6	2
Headache	21.2	0.6	2
Diarrhea	20.6	1.2	2
Pneumonia	20.0	15.2	2

4.2. Boxed Warning: Cytokine Release Syndrome (CRS)

CRS is the most common and one of the most serious risks associated with Teclistamab, warranting a Boxed Warning in the U.S. prescribing information.[3] It is a systemic inflammatory response triggered by the massive release of cytokines from activated T-cells and other immune cells.

• Incidence and Severity: In the MajesTEC-1 trial, CRS occurred in 72% of patients receiving the recommended dose.[2] The vast majority of these events were low-grade and manageable: 50% were Grade 1, 21% were Grade 2, and only one patient (0.6%) experienced a transient Grade 3 event. No Grade 4 or fatal CRS events were reported.[7] Recurrent CRS, meaning a new CRS event after resolution of a prior one, was observed in 33% of patients.[35]
• Timing and Duration: The onset of CRS is highly predictable, which is a key aspect of its management. Most events (97%) are confined to the step-up dosing phase and the first full treatment dose.[23] Specifically, 42% of patients experienced their first CRS event after the first step-up dose, 35% after the second step-up dose, and 24% after the first 1.5 mg/kg treatment dose.[35] The median time to onset was 2 days (range: 1 to 6 days) after the most recent dose, and the median duration of the event was 2 days (range: 1 to 9 days).[33]
• Clinical Presentation: The signs and symptoms of CRS are characteristic of a systemic inflammatory state and include fever (≥38°C or 100.4°F), hypoxia (low oxygen levels), chills, hypotension (low blood pressure), sinus tachycardia (fast heart rate), headache, and elevated liver enzymes.[33]
• Management: Management of CRS is proactive and grade-dependent, guided by established protocols such as those from the American Society for Transplantation and Cellular Therapy (ASTCT). Key strategies include the mandatory step-up dosing schedule and premedications to blunt the initial cytokine peak. At the first sign of CRS, patients require immediate evaluation and supportive care, which may include intravenous fluids, oxygen supplementation, and vasopressors for hypotension.[34] For moderate to severe CRS, specific immunomodulatory therapies are used. Tocilizumab, a monoclonal antibody that blocks the IL-6 receptor, is the primary intervention for Grade 2 or higher CRS. Corticosteroids, such as dexamethasone, are also used, particularly for more severe or refractory cases.[38] Dosing of Teclistamab is withheld until the CRS event resolves and is permanently discontinued for severe (Grade 4) events.[41] A detailed grading and management summary is provided in Table 5.

Table 5: Detailed Grading and Management of Cytokine Release Syndrome (CRS)

CRS Grade	Clinical Definition	Recommended Management Action
Grade 1	Temperature ≥38°C.	• Withhold Teclistamab until CRS resolves. • Provide supportive care (antipyretics, IV fluids). • Monitor closely.
Grade 2	Temperature ≥38°C with either: • Hypotension responsive to fluids (no vasopressors needed), OR • Oxygen requirement of low-flow nasal cannula.	• Withhold Teclistamab until CRS resolves. • Administer Tocilizumab 8 mg/kg IV. • Administer Dexamethasone 10 mg IV/PO (if no improvement). • Provide supportive care.
Grade 3	Temperature ≥38°C with either: • Hypotension requiring one vasopressor, OR • Oxygen requirement of high-flow nasal cannula or face mask.	• Withhold Teclistamab until CRS resolves. • Administer Tocilizumab 8 mg/kg IV. • Administer Dexamethasone 10 mg IV q6h. • Provide supportive care, may require ICU admission.
Grade 4	Temperature ≥38°C with either: • Hypotension requiring multiple vasopressors, OR • Oxygen requirement of positive pressure ventilation (e.g., BiPAP, intubation).	• Permanently discontinue Teclistamab. • Administer Tocilizumab and high-dose corticosteroids. • Provide intensive supportive care in an ICU setting.

Sources: [38]

4.3. Boxed Warning: Neurologic Toxicity and ICANS

The second component of the Boxed Warning is for neurologic toxicity, including the specific and potentially life-threatening syndrome known as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).[3]

• Incidence and Severity: Some form of neurologic toxicity occurred in 57% of patients treated with Teclistamab.[2] The most frequent events were generally mild to moderate and included headache (25%), motor dysfunction (e.g., tremor, dysgraphia; 16%), sensory neuropathy (e.g., numbness, tingling; 15%), and encephalopathy (13%).[33] Severe (Grade 3 or 4) neurologic toxicity was much less common, occurring in 2.4% of patients.[2] With longer follow-up, rare but very serious events, including a case of Grade 4 seizure and a fatal case of Guillain-Barré syndrome, were reported.[34] ICANS specifically was reported in 6% of patients, with the majority of cases being Grade 1 or 2. Recurrent ICANS occurred in 1.8% of patients.[2]
• Timing and Duration: Similar to CRS, the onset of ICANS is typically early in the treatment course. Most cases occurred following one of the three step-up doses.[35] The median time to onset of ICANS was 4 days (range: 2 to 8 days) after the most recent dose, with a median duration of 3 days (range: 1 to 20 days).[35] ICANS can occur concurrently with, following, or in the absence of CRS.[20]
• Clinical Presentation: The symptoms of ICANS can be varied and are assessed using standardized tools like the Immune Effector Cell-Associated Encephalopathy (ICE) score. Clinical manifestations include confusion, disorientation, aphasia (difficulty with speech), dysgraphia (changes in handwriting), depressed level of consciousness, seizures, and motor weakness.[11]
• Management: Management of neurotoxicity is also grade-dependent. At the first sign of any neurologic symptoms, Teclistamab should be withheld, and a neurologic evaluation should be considered to rule out other causes.[22] For ICANS, management is guided by the severity grade. Grade 1 typically involves withholding the drug and close monitoring. For Grade 2 or higher ICANS, corticosteroids (e.g., dexamethasone 10 mg IV every 6 hours) are the mainstay of treatment, along with supportive care, which may include intensive care and anti-seizure medication prophylaxis.[22] Teclistamab is permanently discontinued for severe or recurrent neurotoxic events.[22] Due to the risk of depressed consciousness, patients are strictly advised to refrain from driving or operating heavy or potentially dangerous machinery during the entire step-up dosing schedule and for 48 hours after its completion, and at any time if new neurologic symptoms develop.[36] A summary of management is in Table 6.

Table 6: Detailed Grading and Management of Neurologic Toxicity, including ICANS

Grade	Clinical Definition (based on ICE Score / Symptoms)	Recommended Management Action
Grade 1	ICE Score 7-9, or mild symptoms (e.g., mild confusion, tremor).	• Withhold Teclistamab until symptoms resolve to Grade ≤1 or stabilize. • Monitor neurologic symptoms closely. • Consider neurology consultation.
Grade 2	ICE Score 3-6, or moderate symptoms (e.g., aphasia, significant lethargy).	• Withhold Teclistamab until symptoms improve to Grade ≤1. • Administer Dexamethasone 10 mg IV q6h; taper upon resolution. • Provide supportive therapy; consider anti-seizure prophylaxis.
Grade 3	ICE Score 0-2, or severe symptoms (e.g., seizures, depressed consciousness awakening only to tactile stimulus).	• Withhold Teclistamab until symptoms improve to Grade ≤1. • Administer Dexamethasone 10 mg IV q6h; taper upon resolution. • Provide intensive supportive care, likely in an ICU setting.
Grade 4	ICE Score 0, or life-threatening symptoms (e.g., stupor, coma, life-threatening seizures). OR Recurrent Grade 3	• Permanently discontinue Teclistamab. • Administer Dexamethasone and provide intensive supportive care.

Sources: [22]

4.4. Other Clinically Significant Toxicities

While CRS and neurotoxicity are the focus of the Boxed Warning, other serious toxicities contribute significantly to the overall risk profile of Teclistamab.

• Infections: Infections represent a major cause of morbidity and mortality. In MajesTEC-1, infections of any grade occurred in 76.4% of patients, with a high rate of severe (Grade 3-4) infections at 44.8%.[7] Serious infections, including pneumonia and sepsis, were reported in 30% of patients, and fatal infections occurred in 4.2%.[33] The high risk of infection is multifactorial, driven by the underlying disease, prior treatments, and direct effects of Teclistamab, including profound and prolonged neutropenia and hypogammaglobulinemia (low antibody levels). Hypogammaglobulinemia was reported in over 70% of patients.[2] Management strategies are crucial and include monitoring immunoglobulin levels with consideration for intravenous immunoglobulin (IVIG) replacement therapy, monitoring for signs of infection, and the use of prophylactic antimicrobials (e.g., antiviral prophylaxis for herpes zoster) per institutional guidelines.[20]
• Hematologic Toxicities: Severe, Grade 3-4 cytopenias were extremely common, reflecting the drug's potent impact on the bone marrow microenvironment. Grade 3-4 neutropenia was observed in 64.2% of patients, anemia in 37.0%, and thrombocytopenia in 21.2%.[7] Management involves regular monitoring of complete blood counts and providing supportive care as needed, such as granulocyte-colony stimulating factor (G-CSF) for neutropenia and blood or platelet transfusions.[22]
• Hepatotoxicity: Teclistamab can cause liver injury. Elevations in liver enzymes (AST/ALT) were reported in approximately 30-34% of patients, with severe (Grade 3-4) elevations in 1.2%.[14] Importantly, there has been one fatal case of hepatic failure attributed to the therapy.[34] Consequently, monitoring of liver function tests at baseline and periodically during treatment is required.[14]

The overall safety data reveals an important distinction between the acute and long-term risks of Teclistamab. The acute, on-target toxicities of CRS and ICANS are dramatic and drive the need for the REMS program and initial hospitalization. However, they are generally predictable in timing, mostly low-grade, and have well-defined management protocols. In contrast, the risk of severe and life-threatening infection is a more insidious and persistent threat that continues throughout the course of therapy. This risk, driven by the profound immunosuppression from neutropenia and hypogammaglobulinemia, may ultimately be a greater contributor to overall morbidity and mortality. This suggests that while institutional readiness for CRS/ICANS is paramount for initiating therapy, the long-term clinical management burden will be heavily focused on infection prophylaxis, surveillance, and rapid intervention.

Furthermore, emerging real-world data indicating potentially lower rates of CRS in patients who have received prior T-cell redirecting therapies carries significant implications.[43] The 72% CRS rate observed in MajesTEC-1 was in a T-cell therapy-naïve population. If subsequent studies confirm that prior exposure blunts the initial cytokine release, it could open the door to investigating modified, less intensive monitoring protocols (e.g., outpatient step-up dosing) for this specific subgroup. Such a change would dramatically reduce the logistical and cost burden of treatment, thereby improving the drug's accessibility and convenience.

Section 5: Dosing, Administration, and Risk Mitigation

5.1. Recommended Dosing Regimen

The dosing and administration of Teclistamab are highly structured and standardized to maximize safety, particularly to mitigate the risk of severe CRS. Adherence to this regimen is mandatory.

• Route of Administration: Teclistamab is for subcutaneous (SC) injection only and should be administered by a qualified healthcare professional.[2]
• Step-up Dosing Schedule: Treatment must be initiated with a weight-based, three-step ramp-up schedule over the course of approximately one week.[3] This approach allows for gradual T-cell engagement, which has been shown to reduce the incidence and severity of CRS. The schedule is as follows:
• Day 1 (Step-up dose 1): 0.06 mg/kg
• Day 4 (Step-up dose 2): 0.3 mg/kg. This dose may be given between 2 and 7 days after the first dose to allow for resolution of any adverse reactions.
• Day 7 (First treatment dose): 1.5 mg/kg. This is the first full therapeutic dose and may be given between 2 and 7 days after the second step-up dose.
• Maintenance Dosing: Following the completion of the step-up schedule, the maintenance dose is 1.5 mg/kg administered subcutaneously once weekly.[3] Treatment is continued until disease progression or unacceptable toxicity.
• Biweekly Dosing Option: A significant development in the administration of Teclistamab is the option for a less frequent dosing interval for patients with a deep and sustained response. For patients who achieve a complete response (CR) or better and maintain that response for a minimum of 6 months, the dosing frequency may be decreased to 1.5 mg/kg every two weeks (biweekly).[22] This option can reduce the treatment burden for long-term responders.

The precise, multi-step dosing schedule is a critical safety feature of the drug. A clear summary is provided in Table 7 to facilitate correct administration.

Table 7: Teclistamab Dosing and Administration Schedule

Phase	Day of Treatment	Dose (based on actual body weight)	Key Administration Notes
Step-up Dosing	Day 1	0.06 mg/kg SC	First step-up dose.
	Day 4 (approx.)	0.3 mg/kg SC	Second step-up dose. May be given 2-7 days after Dose 1.
	Day 7 (approx.)	1.5 mg/kg SC	First full treatment dose. May be given 2-7 days after Dose 2.
Weekly Maintenance	Weekly, starting 1 week after first treatment dose	1.5 mg/kg SC	Standard weekly maintenance dosing.
Biweekly Maintenance Option	Every 2 weeks	1.5 mg/kg SC	Option for patients with ≥CR maintained for ≥6 months.

Sources: [41]

5.2. Premedication and Patient Monitoring

To further mitigate risks, a strict protocol of premedication and patient monitoring is required.

• Required Premedications: All patients must receive a combination of premedications administered 1 to 3 hours prior to each of the three doses in the step-up schedule (Day 1, Day 4, and Day 7). The standard premedication regimen includes [14]:
• A corticosteroid: Dexamethasone 16 mg (oral or intravenous)
• An H1-receptor antagonist: Diphenhydramine 50 mg or equivalent (oral or intravenous)
• An antipyretic: Acetaminophen 650 mg to 1000 mg (oral or intravenous) Premedication may also be required for subsequent doses if a patient experienced CRS with their previous dose or if they are restarting the step-up schedule after a significant dose delay.41
• Mandatory Hospitalization: Due to the high risk of CRS and neurologic toxicity during the initial phase of treatment, patients must be hospitalized for a minimum of 48 hours after the administration of all doses within the step-up dosing schedule.[22] This allows for intensive monitoring and rapid medical intervention if severe toxicities arise.
• Prophylaxis: Given the high rate of infections and the risk of viral reactivation in immunosuppressed patients, clinicians should consider initiating antiviral prophylaxis (e.g., for herpes zoster virus) prior to starting Teclistamab, in accordance with local institutional guidelines.[36]

5.3. The TECVAYLI and TALVEY™ REMS Program

In the United States, the FDA has mandated that Teclistamab be available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS).[3] This program, named the TECVAYLI and TALVEY REMS (as it also covers the bispecific antibody talquetamab), is designed to ensure that the benefits of the drug outweigh the significant risks of CRS and neurologic toxicity. Key elements of the REMS program include:

• Prescriber and Facility Certification: Healthcare providers who prescribe Teclistamab and the facilities where it is administered must be specially certified in the REMS program. This involves training on the risks and proper management of CRS and ICANS.
• Patient Counseling: Prescribers must counsel patients on the risks of CRS and neurologic toxicity, the symptoms to watch for, and the requirement for hospitalization during the step-up phase.
• Pharmacy Certification: Pharmacies that dispense Teclistamab must also be certified and can only dispense the drug to certified healthcare facilities.

Section 6: Regulatory and Development History

6.1. Path to Approval in the United States (FDA)

The regulatory journey of Teclistamab in the U.S. was expedited due to its potential to address a critical unmet need in RRMM.

• Timeline and Designation: Recognizing its promising early data, the FDA granted Teclistamab Breakthrough Therapy Designation in May 2021.[8] This designation is intended to expedite the development and review of drugs for serious conditions where preliminary evidence indicates a substantial improvement over available therapies. Janssen submitted the Biologics License Application (BLA) to the FDA in December 2021.[47]
• Approval: On October 25, 2022, the FDA granted Accelerated Approval to teclistamab-cqyv.[2] The accelerated approval pathway allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint—in this case, the overall response rate and duration of response from the single-arm MajesTEC-1 trial.
• Indication and Contingency: The approved indication is for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.[3] A critical condition of the accelerated approval is that continued approval for this indication may be contingent upon the verification and description of clinical benefit in confirmatory clinical trials.[3]

6.2. Path to Approval in Europe (EMA)

Teclistamab's path to market in Europe ran parallel to its U.S. review, also utilizing expedited regulatory mechanisms.

• Timeline and Designation: The European Medicines Agency (EMA) supported the drug's development through its PRIority MEdicines (PRIME) scheme, which provides enhanced scientific and regulatory support to promising medicines for unmet needs.[48] The Committee for Medicinal Products for Human Use (CHMP) reviewed the application under an accelerated assessment and adopted a positive opinion recommending approval in July 2022.[2]
• Approval: On August 23, 2022, the European Commission granted a Conditional Marketing Authorisation (CMA) for Tecvayli, which marked the drug's first approval worldwide.[2] The CMA is analogous to the FDA's accelerated approval, granted on the basis of less comprehensive data than normally required when the benefit of a medicine's immediate availability outweighs the risk of having incomplete data.
• Indication and Contingency: The European indication is slightly broader, for the treatment of adult patients with RRMM who have received at least three prior therapies (including a PI, IMiD, and anti-CD38 mAb) and have demonstrated disease progression on the last therapy.[6] As a condition of the CMA, the marketing authorization holder (Janssen) is required to provide comprehensive clinical data from ongoing confirmatory trials to confirm the drug's benefit-risk profile.[6]

The parallel use of these expedited pathways by two major, independent regulatory agencies highlights a global consensus on two critical points. First, it underscores the severity of the unmet medical need in the triple-class exposed RRMM population, for whom effective options were extremely limited. Second, it signals a strong agreement on the compelling nature of the efficacy and durability data from the single-arm MajesTEC-1 trial, which was deemed sufficient to justify market entry despite the lack of randomized, controlled Phase 3 data at the time of approval.

6.3. Global Regulatory Status and Market Access Issues

Beyond the U.S. and EU, Teclistamab has gained acceptance in other regions, such as its approval for use in Scotland by the Scottish Medicines Consortium (SMC) in September 2024.[51] However, the drug's journey has also highlighted challenges that extend beyond regulatory approval.

A notable case study in market access has emerged in Germany. Despite receiving EMA approval, which makes it legally marketable throughout the European Union, the manufacturer Janssen announced a decision to postpone the launch of Tecvayli in the German market.[52] The company cited challenges with Germany's health technology assessment (HTA) and reimbursement system, the AMNOG (Arzneimittelmarktneuordnungsgesetz). Janssen stated that the system, which determines the level of reimbursement based on a drug's demonstrated added benefit over a specified comparator, does not adequately recognize the clinical value of innovative medicines approved on the basis of single-arm Phase 1/2 evidence.[52]

This situation reveals a critical and growing disconnect between the processes of regulatory approval and reimbursement. While regulators like the FDA and EMA may approve a drug based on a favorable benefit-risk assessment in a population with unmet needs, national HTA bodies often have different and more rigid evidentiary requirements, frequently demanding direct comparative data from randomized controlled trials to justify pricing and reimbursement. The MajesTEC-1 trial's single-arm design, while sufficient for expedited regulatory approval, presented a challenge for the formal HTA process in Germany. This case illustrates that for drug developers, securing regulatory approval is only the first major hurdle; navigating the complex and varied landscape of national pricing and reimbursement systems is a second, and potentially more challenging, step that can ultimately determine whether a safe and effective drug reaches patients in a given country.

Section 7: Strategic Analysis: Place in Therapy and Comparative Landscape

7.1. Comparison with BCMA-Directed CAR T-Cell Therapies

The approval of Teclistamab places it in a dynamic therapeutic landscape alongside two autologous BCMA-directed CAR T-cell therapies: idecabtagene vicleucel (ide-cel, brand name Abecma) and ciltacabtagene autoleucel (cilta-cel, brand name Carvykti). A comparison of these modalities reveals distinct trade-offs in efficacy, safety, and logistics.

• Efficacy: In their respective pivotal trials, the CAR T-cell therapies demonstrated higher overall response rates than Teclistamab. The ORRs for ide-cel and cilta-cel were approximately 73% and 98%, respectively, compared to 63% for Teclistamab.[16] Cilta-cel, in particular, has shown a remarkably long median progression-free survival in its pivotal trial.[16] This suggests that for a patient who is a suitable candidate and has access, CAR T-cell therapy may offer a higher probability of a deep and potentially more durable response.
• Safety: While all three therapies share the mechanism-based toxicities of CRS and ICANS, the incidence and severity of these events appear to be higher with CAR T-cell therapies. In their pivotal trials, CRS rates were 84% for ide-cel and 95% for cilta-cel, with higher rates of Grade ≥3 events (5% and 4%, respectively) compared to Teclistamab (0.6%).[16] Similarly, ICANS rates were higher with ide-cel (18%) and cilta-cel (17%) than with Teclistamab (6%).[16] CAR T-cell therapy also carries a risk of prolonged, multi-lineage cytopenias (termed immune effector cell-associated hematotoxicity, or ICAHT) that can persist for months after infusion, a toxicity that is less pronounced with bispecific antibodies.[54]
• Logistics and Accessibility: This is the domain where Teclistamab holds a decisive advantage. As an "off-the-shelf" product, it is a standardized, readily available pharmaceutical that can be administered promptly after a treatment decision is made.[16] In contrast, CAR T-cell therapy is a highly personalized and complex process. It requires harvesting the patient's own T-cells via leukapheresis, shipping them to a centralized manufacturing facility for genetic engineering and expansion, and then shipping them back for infusion into the patient. This entire process can take four to six weeks or longer, during which the patient's disease may progress, often necessitating "bridging" chemotherapy.[16] Furthermore, there is a risk of manufacturing failure, and access to the therapy is restricted to a limited number of specialized, certified treatment centers.[21]

This comparison indicates that Teclistamab's primary competitive advantage is not superior efficacy, but rather superior logistics, accessibility, and a potentially more manageable short-term toxicity profile. It fills a critical clinical gap for patients who are not ideal candidates for CAR T-cell therapy, those who cannot afford the wait time associated with manufacturing, or those with rapidly progressing disease that demands immediate therapeutic intervention. In essence, Teclistamab democratizes access to potent T-cell redirecting immunotherapy for a broader population of RRMM patients.

7.2. Comparison with Other BCMA-Directed Therapies

Teclistamab also competes with other non-CAR-T therapies targeting BCMA and other antigens.

• Belantamab Mafodotin (ADC): This antibody-drug conjugate, which targets BCMA to deliver a cytotoxic payload, was voluntarily withdrawn from the U.S. market after its confirmatory trial failed to meet its primary endpoint, but it remains available in other regions. Indirect comparisons suggest that Teclistamab offers higher and deeper response rates.[16] The unique toxicity of belantamab is ocular, specifically keratopathy, which is not associated with Teclistamab.
• Elranatamab (Bispecific): Elranatamab is another subcutaneously administered BCMAxCD3 bispecific antibody with a very similar mechanism of action, efficacy profile, and safety profile to Teclistamab.[55] It represents a direct, "me-too" competitor in the same therapeutic class.
• Talquetamab (Bispecific): Talquetamab is a bispecific T-cell engager that targets a different antigen on myeloma cells: G protein-coupled receptor, class C group 5 member D (GPRC5D).[4] This makes it a critically important therapeutic option, as it provides a non-BCMA-directed T-cell redirecting therapy. It is a key agent for patients who have relapsed after receiving a BCMA-targeted therapy, allowing for a switch in antigen target to overcome potential BCMA-related resistance mechanisms.

A comparative overview of these key agents is presented in Table 8.

Table 8: Comparative Overview of Key Immunotherapies for RRMM

Therapy (Brand Name)	Target	Modality	ORR (%)	≥CR Rate (%)	Key Toxicities	Administration Logistics
Teclistamab (Tecvayli)	BCMA x CD3	Bispecific Ab	63	39	CRS (72%), ICANS (6%), Infections	Off-the-shelf, SC injection, step-up hospitalization
Idecabtagene vicleucel (Abecma)	BCMA	CAR T-cell	73	33	CRS (84%), ICANS (18%), Prolonged Cytopenias	Autologous manufacturing (weeks), IV infusion, specialized centers
Ciltacabtagene autoleucel (Carvykti)	BCMA	CAR T-cell	98	83	CRS (95%), ICANS (17%), Prolonged Cytopenias	Autologous manufacturing (weeks), IV infusion, specialized centers
Elranatamab (Elrexfio)	BCMA x CD3	Bispecific Ab	61	37	CRS (61%), ICANS (6%), Infections	Off-the-shelf, SC injection, step-up hospitalization
Talquetamab (Talvey)	GPRC5D x CD3	Bispecific Ab	72	32	CRS (72%), Skin/Nail toxicity, Dysgeusia	Off-the-shelf, SC injection, step-up hospitalization

Sources:.[7] Data are from respective pivotal trials and are not from head-to-head comparisons.

7.3. Sequencing and Clinical Considerations

The proliferation of highly effective T-cell redirecting therapies has transformed the management of RRMM, but it has also introduced the complex clinical challenge of treatment sequencing. Since these therapies produce deep but ultimately finite responses in most patients, relapse is expected, and a long-term strategy is required.

The current clinical thinking, though still evolving and not yet supported by randomized trial data, suggests a potential sequencing pathway. For a young, fit patient with good organ function and access to a specialized center, initiating treatment with a high-efficacy CAR T-cell therapy like cilta-cel may be preferred to maximize the potential for a deep, long-lasting, treatment-free remission.[56] Upon relapse, the optimal next step might be to switch to a bispecific antibody that targets a different antigen, such as the GPRC5D-directed talquetamab, to circumvent any BCMA-related resistance mechanisms.[56] Following progression on that agent, one could then consider returning to the BCMA target with a bispecific antibody like Teclistamab. The data from MajesTEC-1 Cohort C and other real-world studies showing activity of Teclistamab after prior BCMA therapy supports its use in this later-line setting.[27]

The approval of Teclistamab and its counterparts is not an endpoint but rather the beginning of a new, more complex era in myeloma therapy. The focus of the field must now expand beyond the development of single agents to understanding the mechanisms of resistance that lead to relapse. Future progress will depend on biomarker research—analyzing factors like T-cell fitness, levels of target antigen expression, and the tumor microenvironment—to guide these sequencing decisions rationally and to develop effective combination strategies that can prevent or overcome resistance, with the ultimate goal of turning deep responses into cures.

Section 8: Conclusion and Future Directions

8.1. Summary of Clinical Value

Teclistamab (Tecvayli) is a transformative therapeutic agent for patients with heavily pretreated relapsed and refractory multiple myeloma. As the first-in-class approved BCMAxCD3 bispecific T-cell engager, it offers a high probability of achieving a deep and durable clinical response in a patient population that has exhausted standard therapies and faces a dismal prognosis. The pivotal MajesTEC-1 trial demonstrated an overall response rate of 63%, with a median duration of response exceeding 18 months, representing a paradigm shift in outcomes for this setting.

This profound efficacy is balanced by a significant and complex safety profile. The therapy carries Boxed Warnings for Cytokine Release Syndrome and neurologic toxicity, including ICANS. These on-target, mechanism-based toxicities are predictable, occur primarily during the initial dosing phase, and are manageable with a strict protocol of step-up dosing, premedication, and mandatory hospitalization. The long-term risk of serious and fatal infections, driven by drug-induced immunosuppression, remains a major clinical challenge requiring vigilant monitoring and prophylaxis. The entire treatment paradigm is governed by a restricted REMS program to ensure the benefits outweigh the risks.

Strategically, Teclistamab's most crucial advantage is its "off-the-shelf" nature. This provides a powerful, effective, and immediately accessible T-cell redirecting therapy, positioning it as a vital alternative for patients for whom autologous CAR T-cell therapy is not a feasible or timely option.

8.2. Ongoing Research and Future Outlook

The journey of Teclistamab is far from over. Its current accelerated and conditional approvals are contingent upon the results of ongoing Phase 3 confirmatory trials. Studies like MajesTEC-3 (NCT05083169) are evaluating Teclistamab against standard-of-care regimens in earlier lines of therapy, with the goal of moving this potent agent into less heavily pretreated patient populations.[55]

The future of Teclistamab will also be defined by its use in combination regimens. Numerous clinical trials are currently underway exploring Teclistamab combined with other established myeloma agents, such as the anti-CD38 antibody daratumumab (in the TRIMM-2 and MajesTEC-2 trials) and immunomodulatory drugs like lenalidomide.[16] The goal of these combinations is to leverage synergistic mechanisms to deepen initial responses, overcome intrinsic or acquired resistance, and prolong disease control.

Finally, research continues to optimize the administration and safety of Teclistamab itself. Studies investigating the prophylactic use of tocilizumab to further reduce the incidence of CRS, and the potential for safe outpatient administration of the step-up doses in select patient populations, could substantially reduce the treatment burden, cost, and logistical complexity associated with the therapy.[25] As the treatment landscape for multiple myeloma continues to evolve, Teclistamab is poised to remain a cornerstone of therapy, integrated into rational, biomarker-driven combination and sequencing strategies with the aim of progressively improving outcomes for all patients with this challenging disease.

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