Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody

Figures & data

Table 1 Comparison of Approved T Cell-Redirecting Therapies

Agent	Trial	%EMD	%Triple-Class Refractory	Median LOT	ORR	Median PFS	CRS, Any Grade (Grade ≥3)	ICANS, Any Grade (Grade ≥3)
Teclistamab (Tecvayli)	MajesTEC-1^Citation3	17%	77.6%	5	63.0%	11.3	72.1% (0.6%)	3% (0%)
Ide-cel (ABECMA^®)	KarMMa^Citation36	39.1%	84.4%	6	73.4%	8.8	84% (5%)	18% (3%)
Cilta-cel (CARYVKTI^®)	CARTITUDE-1^Citation37,Citation38	13.4%	87.6%	6	96.9%	34.9	95% (4%)	17% (2%)

Table 2 Agents Utilized for Cytokine Release Syndrome

Agent	Starting Dose	Target/Mechanism	Pros/Cons
Tocilizumab	8 mg/kg	IL-6 receptor	Pros: No direct effect on T cell viability,^Citation54 efficacious with large body of evidence Cons: Poor CNS penetration, high cost
Corticosteroids	Grade 1 CRS – dexamethasone 10 mg PO/IV daily Grade 2/3 CRS - dexamethasone 10–20 mg IV every 6 hours Grade 4 - methylprednisolone 1–2 g IV daily	Varied mechanisms including downregulating inflammatory pathways and inducing lymphocyte apoptosis	Pros: Efficacious with large body of evidence, low cost Cons: Potential to hamper efficacy of T-cell redirection
Anakinra	100–200 mg SC q8h	IL-1 receptor	Pros: Preserves T cell function,^Citation55 crosses blood-brain barrier and may be effective for both CRS and ICANS^Citation56 Cons: Limited data for CRS treatment
Siltuximab	11 mg/kg x1	IL-6	Pros: Comparable efficacy to tocilizumab in small retrospective studies,^Citation57 long half-life (21 days) Cons: Limited data compared to tocilizumab, high cost
Etanercept	25 mg SC BIW	TNF-α	Pros: Efficacious for TNF-α-driven CRS,^Citation51 well-established safety in other settings (RA) Cons: Limited data for CRS treatment
Sarilumab	400 mg IV x1	IL-6 receptor	Pros: Same target as tocilizumab, potential substitute in shortages Cons: Clinical data primarily in COVID-19
Ruxolitinib	5 mg BID	Janus kinase 1 and 2	Pros: Preserves T cell viability^Citation58 Cons: Limited data for CRS treatment
Etoposide	150 mg/m^2 IV BIW	Topoisomerase II	Pros: Preferred for CRS with hemophagocytic lymphohistiocytosis (HLH) Cons: Myelosuppressive, kills activated T cells^Citation59
Emapalumab	1 mg/kg IV BIW	IFNγ	Pros: Preferred for CRS with hemophagocytic lymphohistiocytosis (HLH) Cons: Data in CRS limited to case reports

Table 3 Ongoing Trials of Teclistamab in Myeloma

Agent(s)	Disease Setting	Phase	Clinical Trial ID	Status
Teclistamab	RRMM, ≥3 prior LOT	1/2	NCT04557098	Recruiting
Teclistamab vs Rd	High risk smoldering myeloma	2	NCT05469893	Recruiting
Teclistamab vs PVd or Kd	RRMM, 1–3 prior LOT	3	NCT05572515	Recruiting
Teclistamab or talquetamab with PD-1 inhibitor	RRMM, no further established therapies	1	NCT05338775	Recruiting
Teclistamab with various therapies (multi-armed): daratumumab, lenalidomide, pomalidomide, bortezomib, nirogacestat	NDMM or RRMM	1	NCT04722146	Active, not recruiting
Maintenance teclistamab with lenalidomide and teclistamab alone vs lenalidomide after ASCT	NDMM	3	NCT05243797	Recruiting
Teclistamab with daratumumab with/without pomalidomide and talquetamab with daratumumab	RRMM, ≥3 prior LOT	1	NCT04108195	Active, not recruiting
Teclistamab with daratumumab vs DPd or DVd	RRMM, 1–3 prior LOT	3	NCT05083169	Recruiting
Teclistamab with daratumumab, lenalidomide, dexamethasone with/without bortezomib	NDMM	2	NCT05695508	Recruiting
Teclistamab with daratumumab, lenalidomide vs DRd	NDMM	3	NCT05552222	Recruiting
Teclistamab with talquetamab	RRMM, no further established therapies	1/2	NCT04586426	Recruiting

Abbreviations: Rd, lenalidomide, dexamethasone, PVd, pomalidomide, bortezomib, dexamethasone, Kd, carfilzomib, dexamethasone, DPd, daratumumab, pomalidomide, dexamethasone, DVd, daratumumab, bortezomib, dexamethasone, DRd, daratumumab, lenalidomide, dexamethasone.

Table 4 Clinical Trials of T Cell-Engaging Antibodies (Monotherapy)

Agent	Targets	Configuration	Phase	Clinical Trial ID	Status
Talquetamab	GPRC5DxCD3	1:1	II	NCT04634552	Recruiting
Elranatamab	BCMAxCD3	1:1	II	NCT04649359	Active, not recruiting
Alnuctamab (CC-93269)	BCMAxCD3	2:1	I	NCT03486067	Recruiting
Forimtamig (RG-6234)	GPRC5DxCD3	2:1	I	NCT04557150	Recruiting
Linvoseltamab (REGN5458)	BCMAxCD3	1:1	I/II	NCT03761108	Active, not recruiting
ISB-1342	CD38xCD3	1:1	I	NCT03309111	Recruiting
Cevostamab	FcRH5xCD3	1:1	I	NCT03275103	Recruiting
ABBV-383	BCMAxCD3	2:1	I/II	NCT03933735	Active, not recruiting
Lava-051	CD1dxVδ2-TCR chain	1:1	I/II	NCT04887259	Active, not recruiting
TNB-383B	BCMAxCD3	2:1	I/II	NCT03933735	Active, not recruiting
Y150	CD38xCD3	1:1	I	NCT05011097	Recruiting
EMB-06	BCMAxCD3	2:2	I/II	NCT04735575	Recruiting

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