Immune-based therapies continue to reshape the treatment landscape for multiple myeloma (MM), with BCMA-directed approaches moving to earlier in the disease course and delivering increasingly durable responses. Kenneth C. Anderson, MD, reviews key data presented at the 2026 ASCO Annual Meeting highlighting advances in BCMA-directed therapy and an emerging in vivo CAR T-cell technology.

Following these presentations, featured expert Kenneth C. Anderson, MD, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Clinical perspectives from Dr Anderson on these findings are presented here.

MM treatment has been revolutionized by immunotherapies. BCMA-directed CAR T cells and bispecific TCEs were initially approved by the US Food and Drug Administration (FDA) for patients who had received 4 or more prior lines of therapy. Moreover, because of the remarkable extent and frequency of response, including measurable residual disease (MRD)–negative responses, these agents are now being moved to earlier in the disease course, giving us more options for patients with relapsed/refractory MM (RRMM).

During a presentation at ASCO 2026, Saad Z. Usmani, MD, MBA, FRCP, FASCO, FACP, gave an update on the phase 1 DREAMM-9 clinical trial evaluating the BCMA-directed ADC belantamab mafodotin in combination with bortezomib, lenalidomide, and dexamethasone as initial therapy for transplant-ineligible patients with newly diagnosed MM (abstract 7503). What Dr Usmani showed was that high response rates could be achieved, with an overall response rate of 83% or higher across cohorts. Higher dose intensity led to greater response rates, whereas lower dose intensity translated into improved tolerability, particularly with less keratopathy and fewer visual adverse events. DREAMM-9 demonstrated that initial intensive treatment using this ADC as part of a quadruplet regimen followed by dose/interval reductions may provide the best of both worlds: high response rates and durable responses.

Other ASCO 2026 presentations focused on data from the phase 3 DREAMM-8 clinical trial evaluating belantamab mafodotin in RRMM. For example, Meletios A. Dimopoulos, MD, presented an update on the cohort with sustained MRD negativity from DREAMM-8, which compared belantamab mafodotin plus pomalidomide and dexamethasone (BPd) with pomalidomide, bortezomib, and dexamethasone (PVd) in patients who had received 1 to 3 prior lines of therapy (abstract 7515). This study had previously demonstrated improvements in progression-free survival (PFS) for patients treated with BPd vs PVd. Here, long-term outcomes showed that including belantamab mafodotin in the triplet treatment resulted in an over 5-fold increased likelihood of achieving sustained MRD negativity compared with PVd (15.5% vs 2.7%, respectively) and that sustained MRD negativity was associated with a durable PFS2 in both arms.

In his second presentation on DREAMM-8 at ASCO 2026, Dr Dimopoulos gave an update on long-term responders (LTRs; abstract 7565). Roughly one-third of patients who received BPd were considered LTRs. Notably, at a median follow-up of 3 years, PFS remained unreached among LTRs, who accounted for 38% of patients treated with BPd vs 15% of those treated with PVd.

Also at this year’s ASCO meeting, Roberto Mina, MD, presented data from the phase 3 MajesTEC-9 clinical trial comparing teclistamab monotherapy with investigator’s choice of PVd or carfilzomib and dexamethasone in patients with RRMM (abstract 7507). Teclistamab monotherapy achieved remarkable activity, with significant improvements in both PFS and overall survival. Of note, infectious prophylaxis is essential when using bispecific TCEs, so viral prophylaxis with acyclovir, bacterial prophylaxis with sulfamethoxazole and trimethoprim, and monthly intravenous immunoglobulin to reduce infection risk are needed. These findings are remarkable because approximately 85% of patients were previously treated with and were refractory to daratumumab. Ultimately, MajesTEC-9 demonstrated that a single-agent bispecific TCE can be active even when a CD38 antibody is used up front.

The increasing use of BCMA-directed therapies earlier in the disease course also highlights the need for additional therapeutic targets. GPRC5D-targeted therapies such as talquetamab and FcRH5-directed bsAbs are highly active, even in the context of prior BCMA exposure. This demonstrates the importance of treatment sequencing. If a patient is eligible for both CAR T-cell therapy and a bsAb and is considering BCMA-directed treatment, current data suggest that CAR T-cell therapy should be considered first because outcomes with CAR T-cell therapy after prior bsAb exposure may be compromised. Conversely, bsAbs directed against alternative targets can remain highly active after prior BCMA-directed therapy.

Finally, one of the most exciting advances presented at ASCO 2026 was an in vivo CAR T-cell therapy. Current CAR T-cell therapy requires T-cell collection, a manufacturing process that takes more than 6 to 8 weeks, and subsequent reinfusion after lymphodepleting chemotherapy. P. Joy Ho, PhD, MBBS, presented updated results from the phase 1 inMMyCAR study of KLN-1010, the first in vivo CAR T-cell therapy for patients with RRMM that generates CAR T cells directly within the patient following a single injection (abstract 7509). This approach produced remarkable complete responses in patients with RRMM, including MRD-negative responses. While durability remains to be determined, the concept is extraordinary. It has the potential to eliminate T-cell collection, manufacturing delays, and lymphodepleting chemotherapy while maintaining the potential benefits of CAR T-cell therapy.

It is truly a remarkable time in MM. BCMA-directed therapies have transformed treatment, and novel immunotherapies are being used earlier on with unprecedented efficacy. These approaches are even being explored in high-risk smoldering MM, raising the possibility that early intervention may one day prevent progression to active disease.