Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
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.
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.
MRD status in MM has unquestionable prognostic informational value, however many questions remain as how to address positive / negative MRD results. Should we de-escalate or stop Rx? When? Can we escalate Rx if + MRD? Which regimen, how long? It will be another few years till objective data are available. I do see value in at least having identification of clonality established upfront for tracking.