Overview of CAR T-cell therapy and bispecific antibodies for relapsed or refractory multiple myeloma with real-world sequencing insights.
Cell Therapy / Resource Centers 07/14/2026

CAR T or Bispecific Antibodies First? Real-World Sequencing Insights in Relapsed/Refractory Multiple Myeloma

A professional headshot of a young businessman in a navy suit and tie, smiling confidently against a neutral gray background. Sawyer Bawek, DO

Key Points

  • In a large European study of patients with relapsed/refractory multiple myeloma (RRMM), initiating treatment with chimeric antigen receptor (CAR) T-cell therapy rather than bispecific antibodies (BsAbs) was associated with improved outcomes.
  • Sequential use of both modalities, either CAR-T followed by BsAb or vice versa, yielded favorable survival trajectories overall.
  • Mortality from early progression was similar regardless of initial modality, highlighting the persistent challenge of disease resistance.
  • The CAR-T benefit was largely driven by ciltacabtagene autoleucel (cilta-cel) and cesnicabtagene autoleucel (cesni-cel), whereas BsAbs performed comparably to idecabtagene vicleucel (ide-cel).
  • Limited access to CAR-T availability in Europe remains a challenge because of systemic and logistical barriers.

The landscape of T-cell engagers (TCEs) in RRMM is rapidly evolving, offering new hope through BCMA-directed CAR-T products and both BCMA- and GPRC5D-targeted BsAbs. However, optimal sequencing and real-world performance remain key questions for clinicians.

A recent study published in Blood Cancer Discovery by Maximilian Merz, MD, of Memorial Sloan Kettering Cancer Center, and colleagues provides real-world insights from 640 patients with RRMM who received these advanced therapies.

Study Design and Methods

This retrospective multicenter analysis examined single-modality and sequential use of the CAR T-cell therapies ide-cel, cilta-cel, and cesni-cel versus BsAbs. Complementary bias-correction methods addressed confounding in this nonrandomized data set.

Clinical Implications and Insights

The real-world findings have several implications for clinical practice:

  • CAR T-cell therapy should be used when feasible: In eligible patients with timely access, initial treatment with CAR T-cell therapy, particularly cilta-cel or cesni-cel, may maximize remission duration and facilitate effective BsAb sequencing at relapse.
  • BsAbs remain essential: BsAbs are highly active after CAR T-cell therapy, and vice versa, making them a critical option for bridging, sequential treatment, or monotherapy in patients who are ineligible for or lack access to CAR T-cell therapy.
  • Treatment resistance continues to be a challenge: Similar mortality from early progression highlights the need for ongoing research into antigen escape, T-cell fitness, and novel targets and combination strategies.
  • Patient selection requires individualized counseling: Treatment selection should account for logistical considerations (eg, apheresis and CAR T-cell manufacturing time vs immediate BsAb availability), toxicity profiles, and patient goals of care. 

This real-world evidence complements pivotal trial data (eg, the KarMMa and CARTITUDE studies and the MajesTEC series) and supports a personalized sequential approach to maximize benefit from both modalities in the RRMM setting. 

However, the study has several limitations, with its retrospective, nonrandomized design introducing selection bias. Additionally, a high proportion of infection-related nonrelapse mortality was observed in the BsAB cohort, which overlapped with the COVID-19 pandemic. 

Although this real-world analysis provides valuable insights, prospective randomized trials on CAR-T versus BsAb sequencing are needed to further define optimal positioning and combinations in RRMM.

Future Directions

As we await prospective randomized data on sequencing and earlier-line integration of TCEs, real-world studies such as this from Merz et al can help refine treatment algorithms. Continued innovation in post-CAR-T bispecifics, dual-targeting approaches, improved manufacturing, and equitable access will be essential to maximize outcomes for patients with RRMM.

Source 

Merz M, Jelinek T, Pabst T, et al. Outcomes of CAR–T cell therapy and bispecific antibodies as single-modality and sequential strategies in relapsed/refractory multiple myeloma. Blood Cancer Discov. Published online June 12, 2026. doi:10.1158/2643-3230.BCD-25-0461