In a phase 1–2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma.
In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab–daratumumab or daratumumab combined with dexamethasone plus the investigator’s choice of pomalidomide (DPd) or bortezomib (DVd) — the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee. Research Summary Teclistamab–Daratumumab in Relapsed or Refractory Multiple Myeloma
A total of 587 patients underwent randomization (291 to receive teclistamab–daratumumab and 296 to receive DPd or DVd). a median of 34.5 months, progression-free survival was significantly longer with teclistamab–daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab–daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P
In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab–daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.)
This is a very impressive signal in a notoriously difficult population—seeing a 79% response rate and median progression-free survival (PFS) of 15.4 months in true extramedullary, triple-class–exposed myeloma is better than expected. Toxicity is real and management-intensive, but the depth and durability of response make this dual-bispecific approach feel like a meaningful advance.
CAR-T therapy outperformed standard of care (SOC) as a second-line treatment, with progression-free survival (PFS) not reached in the CAR-T group compared to 6.2 months in the SOC group. Despite two-thirds of patients crossing over, CAR-T still demonstrated a three-year overall survival rate of 63%, versus 52% with SOC. These are impressive and durable results. The SOC regimen consisted of three cycles of chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant. This positions CAR-T as a viable second-line option for eligible patients.
Guess who’s coming as an option beyond AI (OBI)? Yes—this study showed no safety concerns and demonstrated comparable efficacy.
Quadruplet induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa‑KRd) has reset expectations for transplant‑eligible NDMM and enables measurable residual disease (MRD)‑adapted strategies; MRD‑negativity at 10^-5 is strongly prognostic, and the necessity of autologous stem-cell transplantation (ASCT)—particularly tandem ASCT—amid deep responses is being re‑examined. Practically, MRD‑adapted consolidation after Isa‑KRd suggests no added depth from ASCT in MRD patients and no advantage for tandem ASCT over single ASCT + Isa‑KRd in MRD+ patients. So in day‑to‑day practice, this looks like a chance to de‑escalate transplant intensity while awaiting mature progression-free survival (PFS)/overall survival (OS) data.
The AQUILA trial compared daratumumab to active monitoring in high-risk smoldering multiple myeloma, demonstrating a significant improvement in progression-free survival (PFS) (84% vs 54% at 48 months) and a trend toward better overall survival (OS) (94% vs 86% at 48 months). Dara also achieved a higher rate of deep responses, with 60% of patients reaching minimal residual disease (MRD) negativity compared to none in the monitoring arm. This looks like a game-changer to delay progression, but we’ll need to weigh the toxicity profile carefully in practice and wait for survival data.