To the Editor:
Teclistamab (Tec) and talquetamab (Tal), bispecific CD3 T-cell engagers targeting B-cell maturation antigen (BCMA) and G protein-coupled receptor, class C, group 5, member D (GPRC5D), respectively, have transformed our ability to treat heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients (pts). Tec/Tal are associated with notable early toxicities, including cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS), and the Food and Drug Administration (FDA)-approved label recommends step-up dosing (SUD), pre-medication, and monitoring at a healthcare facility during SUD to mitigate these adverse effects (AEs) [ 1 , 2 ]. While a majority of pts experienced CRS in the registrational MajesTEC-1 and MonumenTAL-1 studies (72% and 80%, respectively), CRS was typically low-grade and predictable in onset with nearly all events occurring during SUD [ 3 , 4 ].
Notable late toxicities of Tec/Tal include hypogammaglobulinemia, myelosuppression, and infections [ 3 , 4 ], which can lead to significant, sometimes fatal complications, leading clinicians to consider de-escalating therapy via extended dosing interval (EDI) treatment [ 5 – 7 ]. In their pivotal trials, Tec was dosed weekly and Tal was dosed weekly or biweekly after SUD, until disease progression or unacceptable toxicity. At these dosing intervals, both FDA-approved labels recommend returning to SUD schedule with pre-medication and monitoring after prolonged delays, regardless of disease response or time on therapy [ 1 , 2 ]. The FDA-approved label for Tec was updated in March 2026 to allow for longer delays before repeat SUD after a post-hoc analysis from MajesTEC-1 demonstrated a very low risk of CRS upon resumption of Tec following dose delay up to 62 days [ 8 ].
Herein, we report a case series of 6 pts who received Tec (5 pts) or Tal (1 pt) with an EDI of 8 or 12 weeks. Between October 2022 and December 2025, pts received a total of 23 doses of Tec or Tal at an EDI (> 28 days) without repeating SUD. Two and 4 pts had been de-escalated to an 8-week and 12-week dosing interval, respectively, with a median of 77 days between doses. All were receiving Tec/Tal on a 4-week dosing interval before EDI.
Patient and disease characteristics are described in Table 1 . Patients had received a median of 26 (16–38) treatment doses prior to EDI transition (Table 1 ), and all pts were confirmed to have a ≥ complete response (CR) before EDI. The reason for EDI was to improve tolerability in 4 pts and per provider discretion based on depth of response for 2 pts (Table 1 ).
Table 1
Patient characteristics and CRS/ICANS after initial SUD and after extended interval without SUD
F, female; M, male; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; SUD, step up doses; EDI, extended dosing interval; Hypogamma, hypogammaglobulinemia; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; BCMA, B-cell maturation antigen; TCR, T-cell redirecting therapy; CR, complete response; sCR, stringent complete response; ADC, antibody–drug conjugate; FcRH5 BsAb, Fc receptor homolog 5 bispecific antibody; CAR-T, chimeric antigen receptor T cell; allo, allogeneic; *Patient with confirmed MRSA bacteremia
| Characteristic | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 |
| Age, years | 82 | 58 | 58 | 72 | 75 | 73 |
| Sex | F | F | F | M | M | M |
| Race | White | White | African American | White | African American | African American |
| ECOG performance status | 1 | 1 | 1 | 1 | 1 | 1 |
| ISS stage | I | I | I | III | III | III |
| Cytogenetic risk | Standard | Standard | Standard | High | Unknown | Standard |
| Isotype | IgA kappa | IgG lambda | IgG kappa | Lambda light chain | IgG kappa | IgG kappa |
| Extramedullary disease | No | No | No | No | No | No |
| Prior BCMA-directed therapy | Yes, ADC | Yes, allo CAR-T | No | No | No | No |
| Prior non-BCMA TCR therapy | Yes, FcRH5 BsAb | No | No | No | No | No |
| Prior lines of therapy, no | 5 | 3 | 1 | 4 | 4 | 1 |
| Time from diagnosis to Tec/Talq, years | 7.1 | 5.6 | 2.8 | 7.2 | 11.5 | 10.0 |
| BsAb Therapy | Tec | Tal | Tec | Tec | Tec | Tec |
| Initial SUD location | Inpatient | Inpatient | Hybrid | Inpatient | Outpatient | Hybrid |
| Treatment doses prior to transition to EDI, no | 16 | 19 | 38 | 30 | 28 | 23 |
| Dosing interval | 12 weeks | 12 weeks | 8 weeks | 12 weeks | 12 weeks | 8 weeks |
| EDI doses received, no | 4 | 2 | 4 | 4 | 4 | 5 |
| Reason for EDI | Depth of response | Depth of response | Tolerance: Infections, fatigue | Tolerance: Infections, cytopenias | Tolerance: Neutropenia, weight loss, hypogamma | Tolerance: Fatigue |
| Change in adverse effects leading to de-escalation after implementation of EDI | – | – | Infections improved Fatigue improved | Infections improved Cytopenias stable | Neutropenia improved Weight loss improved Hypogamma improved | Fatigue improved |
| Hypogamma prior to dose delay | Yes | No | Yes | Yes | Yes | Yes |
| IVIG replacement after EDI | Less frequent | – | Less frequent | Less frequent | Less frequent | Less frequent |
| Disease status at the time of EDI | CR | CR | sCR | sCR | CR | sCR |
| Incidence of CRS/ICANS with initial SUD and after extended interval without SUD | ||||||
| CRS with initial SUD | No | Yes | Yes | Yes | Yes | Yes* |
| Highest grade CRS with initial SUD | – | 2 | 1 | 1 | 1 | 2 |
| Time to onset of CRS from prior dose (days) | – | 1 | 2 | 2 | 1 | 2 |
| Setting of CRS management | – | Inpatient | Inpatient | Inpatient | Outpatient | Inpatient |
| ICANS with initial SUD | No | No | No | No | No | Yes* |
| Highest grade ICANS with initial SUD | – | – | – | – | – | 1 |
| Time to onset of ICANS from prior dose (days) | – | – | – | – | – | 2 |
| Setting of ICANS management | – | – | – | – | – | Inpatient |
| CRS after dose delay(s) without SUD | No | No | No | No | No | No |
| ICANS after dose delay(s) without SUD | No | No | No | No | No | No |
While 5 pts (83%) had experienced CRS and 1 (17%) experienced ICANS during their initial SUD period (Table 1 ), no CRS or ICANS events were observed after any of the 23 EDI doses that were given > 28 days from the last dose without repeating SUD. All pts received pre-medications prior to resuming therapy via EDI (Table 2 ).
Table 2
Doses given at extended interval without SUD
SUD, step up doses; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome
| Characteristic | N = 23 doses |
| Dose-delay interval, days, median (range) | 77 (42–119) |
| Time on Tec/Tal therapy prior to dose delay, days, median (range) | 630 (320–1122) |
| Number of treatment doses received prior to dose delay, median (range) | 28 (16–41) |
| Pre-medications prior to delayed dose, n (%) | 23 (100) |
| • Dexamethasone + diphenhydramine + acetaminophen, n (%) | 11 (48) |
| • Dexamethasone + diphenhydramine, n (%) | 3 (13) |
| • Acetaminophen + diphenhydramine, n (%) | 7 (30) |
| • Dexamethasone, n (%) | 2 (9) |
| CRS, n (%) | 0 (0) |
| ICANS, n (%) | 0 (0) |
Our experience at a large academic medical center of EDI with Tec/Tal is only the second real-world data (RWD) report in the literature. No CRS or ICANS was observed among pts who resumed therapy without repeating SUD despite intervals > 28 days since the last dose. This is consistent with two prior published reports describing no CRS or ICANS in 33 pts who received 62 doses of Tec/Tal with prolonged dosing delay at a single center [ 9 ] and low-grade CRS in only 3.3% of 61 pts who received 81 delayed doses without SUD after prolonged delay in a post-hoc analysis of the MajesTEC-1 population [ 8 ]. Notably, our cohort differs in planned de-escalation to EDI, producing a longer median interval between doses (77 vs. 35 days) compared to Tan and colleagues [ 9 ], attributable to our purposeful transition to EDI. At the time of data cut-off, no pts in our cohort had signs of progressive disease and all remain on therapy with improvement in most AEs which prompted EDI (Table 1 ).
Our report adds to the paucity and contributes to the variability of RWD with purposeful EDI dosing, describing its feasibility and safety in Tec/Tal without repeat SUD, even in pts who experienced CRS or ICANS with initial SUD. Notably, all pts had achieved a ≥ CR and were on therapy for a median of 21 months before EDI dosing, limiting generalizability of these findings to patients with different characteristics. We hypothesize that the apparent lack of recurrent CRS/ICANS observed in our cohort is at least partially explained by reduced tumor burden and sufficient prior exposure to achieve sustained serum concentrations of Tec/Tal, immune desensitization, and altered T-cell activation dynamics [ 8 ]. There is increasing experience with dosing Tec/Tal every 4 weeks driven by treatment response or duration on therapy in RRMM [ 7 , 10 – 12 ]. While all pts in our cohort had achieved ≥ CR, clinicians may want to consider de-escalating therapy with EDI in pts who are experiencing unacceptable AEs on Tec/Tal if they have achieved < CR and have been on therapy for prolonged time, citing similar available reports [ 7 – 9 ]. Further studies of such are necessary to inform application of this de-escalation strategy in varied patient populations.
Given that BsAb therapy may be prolonged in RRMM, providers may consider de-escalating therapy via EDI in select pts who have demonstrated deep and durable responses, or to mitigate late toxicities and improve quality of life. While our study is limited in size and may be viewed as hypothesis-generating, the findings are reassuring as they are consistent with two prior reports of this nature and add to the limited literature that supports the use of EDI without repeating SUD in RRMM pts who are suitable candidates. Further studies are needed to identify patient populations who may benefit from SUD after a prolonged dose delay or EDI de-escalation.
Acknowledgements
Not applicable.
Abbreviations
Teclistamab
Talquetamab
Relapsed or refractory multiple myeloma
Cytokine release syndrome
Immune effector cell-associated neurotoxicity syndrome
Step-up dosing
Bispecific antibody
Patients
Extended dosing interval
Complete response
B-cell maturation antigen
G protein—coupled receptor class C group 5 member D
Food and Drug Administration
Adverse effects
Real-world data
Hypogammaglobulinemia
Eastern Cooperative Oncology Group
International Staging System
Stringent complete response
Chimeric antigen receptor
T-cell redirecting
Allogeneic
Author contributions
All authors were directly involved in writing and revising the manuscript. MB conceived the topic, CB and MB produced the tables, which were reviewed by all authors, MB and SP supervised the project, all other authors reviewed the manuscript and contributed thoughtfully.
Funding
This work received no funding.
Data availability
The deidentified data used in the current report are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Sarah Profitt, Muhamed Baljevic have contributed equally to this work.
References
1. Teclistamab-cqyv (Tecvayli) [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; March 2026.
2. Talquetamab-tgvs (Talvey) [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; October 2025.
3. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387(6):495–505.
4. Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D Bispecific Aantibody for Multiple Myeloma. N Engl J Med. 2022;387(24):2232–44.
5. Chunara F, Lugo C, Osinski K, et al. Real-world treatment patterns for teclistamab and talquetamab in multiple myeloma (MM): experience from 609 patients. Blood Cancer J. 2025;15(1):61.
6. Chakraborty R, Cheruvalath H, Patwari A, et al. Sustained remission following finite duration bispecific antibody therapy in patients with relapsed/refractory myeloma. Blood Cancer J. 2024;14(1):137.
7. Chari A, Oriol A, Krishnan A, et al. Efficacy and Safety of Less Frequent/Lower Intensity Dosing of Talquetamab in Patients with Relapsed/Refractory Multiple Myeloma: Results from the Phase 1/2 MonumenTAL-1 Study [abstract]. Blood. 2023;142(Supplement 1):1010–1.
8. Cardé NAQ, Niu J, Guo Y, et al. Revised Rrecommendations for R estarting T eclistamab F ollowing D ose D elays: I insights from the MajesTEC-1 S tudy on C clinical S afety, and from Simulated P harmacokinetics and C ytokine D ynamics. Target Oncol. 2026;21(3):373–83.
9. Tan CR, Wang A, Nemirovsky D, et al. Restarting teclistamab and talquetamab after prolonged dose delay may not require re-step-up dosing. Blood Adv. 2025;9(13):3331–5.
10. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2026;394(8):739–52.
11. Kumar S, Mateos MV, Ye JC, et al. Dual Targeting of Extramedullary M yeloma with T alquetamab and T eclistamab. N Engl J Med. 2026;394(1):51–61.
12. Mina R, Beksac M, Rodríguez-Otero P, et al. Talquetamab-Daratumumab in Relapsed or Refractory Myeloma. N Engl J Med. 2026. . 10.1056/NEJMoa2604657
Associated Data
Data Availability Statement
The deidentified data used in the current report are available from the corresponding author on reasonable request.