Targeted Agents, Amyloidosis, and Defining a Cure in Plasma Cell Disorders

At the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting, the discussion of plasma cell disorders extended well beyond multiple myeloma to include the emerging role of bispecific antibodies in Waldenström macroglobulinemia (WM) and the evolving landscape of anti-fibril therapies in AL amyloidosis. These concepts appeared alongside urgent questions about how to sequence CAR T-cell therapy and bispecific agents for fit patients with relapsed multiple myeloma, and whether the disease can eventually be considered “cured” in select patients. To better characterize these topics, CancerNetwork® spoke with Meletios Dimopoulos, MD, professor and chairman in the department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, at the meeting in Houston, Texas.¹

Dimopoulos began by contextualizing the exploratory interest in bispecific antibodies for relapsed WM within a disease whose indolent natural history still makes these agents relevant for only a specific subset of patients. He then assessed a kappa light chain–specific subgroup signal from an investigational anti-fibril antibody in AL amyloidosis and placed it within the broader strategy of targeting deposited amyloid rather than just suppressing its production. He addressed where the sequencing debate between CAR T-cell therapy and bispecifics now stands after recent randomized trial data, explained how improved mitigation of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) is enabling bispecific expansion into non-academic settings, and closed by identifying fixed-duration treatment for deep minimal residual disease (MRD)–negative responders as the most important unresolved question. Additionally, he articulated a vision in which multiple myeloma, for some patients, may increasingly be considered a curable disease.

CancerNetwork: Bispecific antibodies such as teclistamab-cqyv (Tecvayli) are now being explored in relapsed WM, an area historically dominated by BTK inhibition and chemoimmunotherapy. How significant a shift is that for a disease that hasn’t seen this kind of option before?

Dimopoulos: First, we have to clarify that [WM] is a relatively indolent disorder with a much better prognosis than that of multiple myeloma. In most patients, disease can be controlled for many years with BTK inhibitors, chemoimmunotherapy, or other agents. There are occasional patients with quite aggressive disease at presentation or at the time of relapse who represent an unmet need. For these patients, there are some exploratory evaluations of bispecific monoclonal antibodies that have been developed from those used in other low-grade lymphomas. I believe it is of interest, but of course this is not a treatment that [most] patients with [WM] may require during the course of their disease.

The kappa light chain–specific subgroup result for the investigational anti-fibril antibody anselamimab in AL amyloidosis has generated real discussion.² How does that finding fit into your broader view of where anti-fibril therapy is heading relative to anti-plasma cell strategies?

For many years, we have focused on treatment strategies that would rapidly reduce the production of the toxic light chains causing amyloid deposits. In recent years, however, attempts have been made to mobilize and increase the degradation of already-deposited amyloid. These anti-fibril amyloid therapies have been investigated, and so far, we have a positive signal with anselamimab, which has shown activity only in patients with kappa light chain amyloidosis, representing approximately 20% of patients with AL amyloidosis. This is an important positive finding that gives us the opportunity to further investigate anti-fibril treatment strategies.

In the relapsed/refractory setting, where do you personally come down on sequencing CAR T-cell therapy vs bispecific antibodies first for a fit, transplant-eligible patient with standard-risk relapse?

Up until a few months ago, we were thinking that CAR T-cell therapy should be prioritized over bispecific monoclonal antibodies. However, recent randomized studies with teclistamab and with talquetamab-tgvs [Talvey] have indicated that these agents, either alone or in combination with other drugs such as daratumumab [Darzalex] or pomalidomide [Pomalyst], may produce very high response rates, very high MRD negativity rates, and impressive progression-free survival. At this point, I believe it is hard to recommend CAR T-cell therapy categorically over bispecifics in early lines of therapy. It is important for our patients and physicians to have both options and to discuss the pros and cons with the patient.

For centers with limited CAR T-cell access, how do you counsel on bispecific-first strategies, and what would need to change to make sequencing genuinely equitable across academic and community settings?

There are several centers where the applicability of CAR T-cell treatment is difficult. However, bispecific-based therapy may be feasible in [more of those settings] because we now have better means and we know how to mitigate CRS and ICANS. This may enable an expansion of bispecific use across centers even outside academic institutions, giving a larger number of patients with multiple myeloma the opportunity to be treated with T cell–engaging therapies.

Looking at multiple myeloma as a whole, what question do you most want to see answered or clarified regarding the use of bispecifics, and what does the future of multiple myeloma management look like to you?

Bispecific antibodies are very effective. However, this comes at a cost: they induce profound immunosuppression, and patients are at risk of developing severe or opportunistic infections. Some of these infections may be prevented by using immunoglobulin replacement, but not all of them. I believe there is a need to identify the best treatment duration. For patients who achieve a very rapid and deep response, especially when we document MRD negativity, fixed-duration treatment with a bispecific antibody may give the patient the opportunity to enjoy a prolonged response while also avoiding the threat of severe infections.

I also want to mention that over the last few years, we are developing the notion of a potential cure for multiple myeloma, meaning that we see an increasing number of patients, especially those with standard-risk disease, who have deep MRD-negative responses and who remain without disease progression for many years. There is a realistic question whether some of these patients may eventually be cured. Definitions of cure are in development; patients who have been off treatment for 5 years and who have been continuously MRD negative may be considered cured. This is a notion we should pay more attention to. Multiple myeloma should not be considered an incurable disease, and we should strive to increase the percentage of patients who enjoy long-term disease-free survival and possibly cure.

References

1. Dimopoulos M. Updates - amyloidosis and WM. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX.
2. Wechalekar AD, Dispenzieri A, Sanchorawala V, et al. Phase 3 randomized trial to evaluate the impact of anselamimab on all-cause mortality in kappa light chain amyloidosis. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX.