It comes as no surprise that bispecific agents are moving up into earlier lines of therapy in multiple myeloma. Here, in the setting of early relapsed, anti-CD38 and –imid exposed patients, single agent teclistimab showed an 18mo progression-free survival benefit over PFd/Kd.
This was a reassuring finding for standard risk nontransplant patients with deep sustained responses, esp those having issues taking lenalidomide. I would be cautious in extrapolating this to high risk or post-transplant patients. This study makes the fixed duration therapy idea more palatable for many of us.
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.
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.
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.
Is the need to transplant declining? Salvage autologous transplant vs lenalidomide/dexamethasone offers no significant survival benefit in RRMM. Patients who relapsed were treated with high-dose chemotherapy followed by maintenance lenalidomide vs dexamethasone and lenalidomide and progression-free survival (PFS) was 20 vs 19 months.
Daratumumab continued to demonstrate single-agent clinical activity in patients with intermediate- or high-risk smoldering myeloma. No new safety concerns were observed after extended follow-up of approximately seven years, highlighting the tolerability of daratumumab. Will need phase III trials.
Direct comparison of Dara+len vs. len maintenance for those with +MMR after Auto-HSCT. MRD-neg conversion rates were higher in the combo arm. This is likely going to continue gaining traction in this group of patients.