La recaída temprana del mieloma múltiple después de MajesTEC-3: menos espera, más preparación

José Ricardo Montenegro Chaves
Departamento de Hematología, Clínica Americana, San José, Costa Rica.

Luis Guillermo Herrera Jiménez
Facultad de Farmacia, Universidad de Costa Rica, San José, Costa Rica.

Resumen

MajesTEC-3 marca un punto de inflexión en el tratamiento del mieloma múltiple recaído o refractario en recaída temprana. En pacientes con una a tres líneas previas, sin exposición previa a BCMA y sin refractariedad a anti-CD38, la combinación de teclistamab y daratumumab mostró una superioridad clínicamente contundente frente a tripletes basados en daratumumab elegidos por el investigador. La supervivencia libre de progresión estimada a 36 meses, las tasas de respuesta completa estricta, la negatividad de enfermedad mínima residual y la supervivencia global respaldan un cambio en la secuenciación terapéutica: las terapias biespecíficas ya no deben reservarse automáticamente para fases tardías de la enfermedad. El argumento central no es solo de eficacia, sino también biológico. Cada recaída implica pérdida de pacientes elegibles, toxicidad acumulada y deterioro progresivo de la competencia inmunitaria, factores que pueden limitar el beneficio de las terapias redirigidas a células T cuando se administran demasiado tarde. Sin embargo, adelantar estos tratamientos exige reconocer con seriedad su perfil de seguridad. En MajesTEC-3, el síndrome de liberación de citocinas fue frecuente pero manejable, mientras que las infecciones graves y mortales subrayan la necesidad de profilaxis, reposición de IgG, vigilancia infecciosa y monitorización sistemática. La reducción de infecciones tras la enmienda del protocolo refuerza que la seguridad depende tanto del fármaco como de la infraestructura asistencial. Después de MajesTEC-3, la pregunta ya no es si los biespecíficos pueden adelantarse, sino si los centros están preparados para administrarlos de manera segura, coordinada y responsable.

Palabras claves

Mieloma múltiple recaído o refractario; MajesTEC-3; teclistamab; daratumumab; anticuerpos biespecíficos; BCMA; infecciones.

Abstract

MajesTEC-3 represents a turning point in the management of early relapsed relapsed or refractory multiple myeloma. In patients who had received one to three prior lines of therapy, were BCMA-naive, and were not refractory to anti-CD38 treatment, the combination of teclistamab and daratumumab demonstrated clinically compelling superiority over investigator-selected daratumumab-based triplets. The estimated 36-month progression-free survival, stringent complete response rates, minimal residual disease negativity, and overall survival support a shift in therapeutic sequencing: bispecific antibody therapy should no longer be reflexively reserved for later stages of disease. The rationale is not only clinical but also biological. Each relapse is associated with patient attrition, cumulative toxicity, declining performance status, and progressive immune dysfunction, all of which may reduce the effectiveness of T-cell– redirecting therapies when they are deployed too late. Earlier use, therefore, may preserve the opportunity for deeper and more durable immunologic remissions. This change, however, requires a clear-eyed approach to safety. In MajesTEC-3, cytokine release syndrome was common but manageable, whereas serious and fatal infections highlight the need for structured prophylaxis, IgG replacement, infection surveillance, and systematic monitoring. The reduction in severe infections after protocol amendment reinforces that safety depends not only on the drug, but also on the care infrastructure surrounding it. After MajesTEC-3, the central question is no longer whether bispecific antibodies can move earlier in relapse. The evidence has answered that. The real challenge is whether institutions are prepared to deliver them safely, consistently, and responsibly.

Keywords

Relapsed or refractory multiple myeloma; MajesTEC-3; teclistamab; daratumumab; bispecific antibodies; BCMA; infections.

Referencias

1. Costa LJ, Bahlis NJ, Perrot A, Nooka AK, Lu J, Pawlyn C, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2026 Feb 19;394(8):739–52. doi:10.1056/NEJMoa2514663

2. Zhu L, Nawaz MA, Zuo Y, Zeng P. Next-generation immunotherapy in relapsed/refractory multiple myeloma: Strategies to achieve sustained MRD negativity. Crit Rev Oncol Hematol. 2025 Oct;214:104913. doi:10.1016/j. critrevonc.2025.104913

3. Fonseca R, Usmani SZ, Mehra M, Slavcev M, He J, Cote S, et al. Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. BMC Cancer. 2020 Dec;20(1):1087. doi:10.1186/s12885-020-07503-y

4. Kumar S, Baizer L, Callander NS, Giralt SA, Hillengass J, Freidlin B, et al. Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee. Blood Cancer J. 2022 Jun 29;12(6):98. doi:10.1038/s41408-022-00695-5

5. Mateos MV, Martínez-López J, Rodriguez Otero P, González-Calle V, Gonzalez MS, Oriol A, et al. Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance. J Clin Oncol. 2024 Sep 20;42(27):3247–56. doi:10.1200/ JCO.23.02771

6. Dimopoulos MA, Terpos E, Boccadoro M, Moreau P, Mateos MV, Zweegman S, et al. EHA–EMN Evidence- Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma. Nat Rev Clin Oncol. 2025  Sep;22(9):680–700.  doi:10.1038/s41571-025-01041-x

7. Rodriguez-Otero P, Usmani S, Cohen AD, Van De Donk NWCJ, Leleu X, Gállego Pérez-Larraya J, et al. International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. Lancet Oncol. 2024 May;25(5):e205–16. doi:10.1016/S1470-2045(24)00043-3

8. Raje N, Anderson K, Einsele H, Efebera Y, Gay F, Hammond SP, et al. Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel. Blood Cancer J. 2023 Aug 1;13(1):116. doi:10.1038/s41408-023-00879-7

9. Lancman G, Parsa K, Kotlarz K, Avery L, Lurie A, Lieberman-Cribbin A, et al. IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies. Blood Cancer Discov. 2023 Nov 1;4(6):440–51. doi:10.1158/2643-3230.BCD-23-0049

10. Mohty M, Malard F, Facon T, Harousseau JL. Toward a cure for multiple myeloma within a decade. Blood Cancer J. 2026 Mar 10;16(1):33. doi:10.1038/ s41408-026-01461-7

11. Food and Drug Administration. FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. FDA [Internet]. 2026 May 5 [cited 2026 May 30]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-combination-daratumumab-hyaluronidase-fihj-relapsed-or-refractory-multiple