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Multiple Myeloma EHA 2026 Commentary
Personalizing Bispecific Antibody Therapy in Multiple Myeloma

Released: July 28, 2026

Ja Min Byun
Ja Min Byun, MD, PhD
Jens Hillengass
Jens Hillengass, MD, PhD
Philippe Moreau
Philippe Moreau, MD
Katja C. Weisel
Katja C. Weisel, MD
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Key Takeaways
  • Bispecific antibodies are expanding beyond triple-refractory disease into settings of earlier relapse, frontline therapy, maintenance, and high-risk smoldering myeloma settings.
  • Personalized treatment decisions, including target selection, sequencing with CAR T-cell therapy, and management of unique toxicity profiles, will increasingly shape optimal patient outcomes.
  • Supportive care, including early CRS management, infection prophylaxis, and IVIG replacement, is essential for maximizing the safety and effectiveness of these therapies.

Bispecific Antibodies in the Multiple Myeloma Treatment Landscape 

Jens Hillengass, MD, PhD
Over the past several years, bispecific antibodies (BsAbs) have generated significant advances in the treatment of relapsed or refractory (R/R) multiple myeloma (MM). Although the current role in treatment is focused on those with heavily pretreated disease, ongoing strategies look to expand their use into earlier lines of therapy, maintenance strategies, and even earlier disease settings such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM. In a recent symposium at the 2026 European Hematology Association congress, we discussed the ongoing and future role of BsAbs in MM and how these therapies are no longer simply an alternative when other options have been exhausted.

With rapid innovation comes new challenges. Determining the optimal sequence of therapies, selecting the right target and partner for combination strategies, minimizing and managing toxicities, and deciding on treatment duration are now among the most important clinical questions we face.

Choosing the Right Target and the Right Patient

Katja C. Weisel, MD
Several BsAbs have demonstrated value in patients with triple-class exposed and triple-class refractory disease, where outcomes have historically been poor. Trials such as MajesTEC-1 (teclistamab), MagnetismMM-3 (elranatamab), and LINKER-MM1 (linvoseltamab) established BCMA-directed agents as highly effective off-the-shelf immunotherapies capable of producing meaningful and durable responses in heavily pretreated patient populations. These studies demonstrated overall response rates (ORRs) ranging from 61% to 71%.

Although BCMA has become the most established target, it is no longer the only option. GPRC5D-directed therapy with talquetamab has expanded our therapeutic toolbox and offers an important alternative, particularly after prior BCMA-directed treatment. Talquetamab demonstrated similar efficacy in the monumenTAL-1 trial, with an ORR of 74% with the weekly dosing schedule and 70% with the every-2-week dosing schedule. Emerging agents targeting FcRH5, including cevostamab, and newer BCMA constructs such as etentamig further illustrate how rapidly this field continues to evolve.

Rather than asking which BsAb is "best," I increasingly find myself asking which target is most appropriate for a given patient. Prior therapies, antigen expression, disease biology, extramedullary disease, anticipated toxicities, and access all influence treatment selection. Patients progressing after BCMA-directed CAR T-cell therapy may still benefit from another BCMA-directed approach if target expression is maintained, whereas others may be better served by switching to GPRC5D-directed therapy. These decisions require thoughtful clinical judgment.

Jens Hillengass, MD, PhD
Equally important, these agents provide an accessible alternative for patients who may not be candidates for CAR T-cell therapy because of manufacturing delays, logistical barriers, or medical comorbidities. Having effective immunotherapy available immediately can make a tremendous difference for patients with rapidly progressive disease.

During the symposium, I led an in-depth case discussion of a patient with aggressive extramedullary disease that highlighted just how individualized these treatment decisions have become. Although no single sequencing strategy has emerged as definitive, my perspective, which I shared with my colleagues during the program, was straightforward: when effective therapies are available, our goal should generally be to use the best option when the patient needs it rather than reserving promising treatments for an uncertain future. If you would like to listen to that discussion, it is linked here.

Expanding Beyond Triple-Class Refractory Disease

Philippe Moreau, MD
What excites me even more, however, is that the story no longer ends in relapsed disease. Clinical development has moved rapidly into earlier relapses, newly diagnosed disease, and even precursor conditions, signaling a fundamental shift in how we may eventually treat MM. In the earlier-line setting, several pivotal phase III trials are already redefining expectations. MajesTEC-3 (NCT05083169) demonstrated impressive outcomes with teclistamab plus daratumumab, achieving a 36-month progression-free survival (PFS) rate of 83.4% compared with 29.7% for standard-of-care daratumumab-based regimens. Similarly, MajesTEC-9 (NCT05572515), which evaluated teclistamab monotherapy in patients previously exposed to both lenalidomide and an anti-CD38 antibody, a population that closely mirrors many of the patients we now see in routine practice, reported an 18-month PFS rate of 69.8% compared with 26.9% for standard therapies.

Similarly, MonumenTAL-3 (NCT05455320) is evaluating talquetamab plus daratumumab with or without pomalidomide, further exploring how BsAbs can be integrated earlier in the treatment continuum and combined with potentially synergistic therapies. At the interim analysis, PFS was significantly longer with talquetamab plus daratumumab and pomalidomide and with talquetamab plus daratumumab than with daratumumab, pomalidomide, and dexamethasone, with estimated 24-month PFS rates of 81.3% and 77.6% vs 51.2%, respectively. MagnetisMM-5 (NCT05020236) is similarly investigating elranatamab alone or in combination with daratumumab, further expanding our understanding of how BsAbs may be incorporated into earlier lines of therapy.

The momentum continues in newly diagnosed disease where studies are challenging long-standing treatment fundamentals. LINKER-MM4 (NCT05828511) is evaluating linvoseltamab as frontline therapy in both transplant-eligible and transplant-ineligible patients, and the TecLille (NCT05572229) study has generated considerable enthusiasm by demonstrating remarkable response rates with a chemotherapy-free combination of teclistamab plus daratumumab in transplant-ineligible patients. MagnetisMM-6 (NCT05623020) is also exploring this evolving treatment landscape by comparing elranatamab plus daratumumab and lenalidomide with the current standard regimen of daratumumab, lenalidomide, and dexamethasone in transplant-ineligible patients with newly diagnosed MM. These early experiences raise important questions about whether highly active immunotherapy combinations may eventually simplify treatment while maintaining exceptional efficacy.

Perhaps even more provocative is the movement into precursor disease. Trials such as Immuno-PRISM (NCT05469893) evaluating fixed-duration teclistamab, LINKER-SMM (NCT05955508) investigating linvoseltamab, and ERASMM (EMN34; NCT06183489) investigating elranatamab are exploring whether intervention in patients with high-risk smoldering MM can achieve deep responses before symptomatic disease develops. Although longer follow-up is clearly needed, these studies reflect an ambitious goal: not simply delaying progression but potentially altering the natural history of the disease.

Sequencing Will Continue to Evolve

Jens Hillengass, MD, PhD
One of the most engaging discussions centered on where BsAbs fit alongside CAR T-cell therapy. Rather than viewing these approaches as competitors, we increasingly see them as complementary. BsAbs can provide valuable bridging therapy (e.g., with the use of talquetamab after lymphapheresis) before CAR T-cell infusion, particularly for patients with aggressive disease. Conversely, CAR T-cell therapy remains an attractive option because of its potential for prolonged treatment-free intervals along with demonstrating curative signals in relapsed disease.  

Katja C. Weisel, MD
As BsAbs move into earlier lines of therapy, sequencing questions become even more important. Ongoing studies evaluating fixed-duration treatment may help preserve future immunotherapeutic options while reducing cumulative toxicity. Likewise, combination strategies, such as the promising results from RedirecTT-1 with teclistamab plus talquetamab for extramedullary disease, suggest that dual-antigen targeting may help overcome resistance in particularly challenging clinical situations. The regimen produced high, durable response rates but was associated with a higher incidence of grade 3 or 4 infections than either therapy alone. Ultimately, we anticipate that biomarkers, disease biology, and response-adapted treatment strategies will increasingly guide these decisions.

Supportive Care Is Essential

Jens Hillengass, MD, PhD
As impressive as the efficacy data are, I would still like to highlight that successful use of BsAbs depends upon intentional, patient-centric supportive care.

For BCMA-directed therapies, infection remains the most clinically significant nonhematologic toxicity. Multiple studies and our collective clinical experience emphasize that infections often occur early but continue to accumulate throughout treatment. Vaccination, antiviral and Pneumocystis prophylaxis, careful monitoring, and particularly intravenous immunoglobulin (IVIG) replacement have become fundamental components of care rather than optional considerations.

The growing evidence supporting proactive IVIG administration is especially compelling. Monitoring IgG levels and initiating replacement before severe hypogammaglobulinemia develops has the potential to substantially reduce serious infections while allowing patients to remain on effective therapy.

It is important to remember that in patients with IgG myeloma, the monoclonal protein should be subtracted from the total IgG level when determining whether IVIG is indicated.

Ja Min Byun, MD, PhD
Similarly, cytokine release syndrome, although common, has become increasingly manageable. Early recognition, prompt intervention, and appropriate use of tocilizumab allow most patients to continue treatment safely. One practical point we emphasized is that healthcare professionals should not hesitate to use tocilizumab early when clinically indicated, recognizing that cytokine release syndrome management for BsAbs differs from CAR T-cell therapy in several important respects.

For GPRC5D-directed therapy, the toxicity profile shifts considerably. Dysgeusia, oral discomfort, skin and nail changes, weight loss, and occasionally neurologic effects require proactive counseling and supportive management. Although these adverse events are generally manageable, they can significantly affect quality of life and deserve careful attention throughout treatment.

Looking Ahead

Jens Hillengass, MD
Perhaps the most exciting aspect of this rapidly changing therapeutic landscape is the possibility that BsAbs may eventually contribute to time-limited treatment approaches, and maybe even functional cure for selected patients. Although I remain appropriately cautious about using that word, the conversation is shifting from simply controlling disease to achieving deep, sustained remissions with treatment strategies that are both effective and tolerable and can ultimately be safely discontinued.

As ongoing phase III studies mature and frontline investigations continue to report results, the challenge will be integrating this expanding body of evidence into thoughtful, individualized patient care.

Your Thoughts
How are you incorporating BsAbs into your treatment algorithms for patients with MM? What are your biggest ongoing challenges with the use of BsAbs in your practice? Have these agents changed your approach to sequencing therapy, managing relapsed disease, or considering frontline treatment strategies?

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