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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.

Retrospective assessment of the SWOG0777 and SWOG 1211 studies showing that dose reductions in dexamethasone did not affect outcomes. Nice to see this does not have a negative impact, as I have been doing this for years in my elderly patients who would not tolerate the ultra-high dose steroids used in these trials.

MRD at year 1 can be prognostic in pt who had AutoBMT followed by maintenance linolidomide. Please use MRD wisely … it can be expensive.

First line regimen, first quad for transplant INELIGIBLE patients, PFS at 5 years is 63% vs 45% for RVD. This will probably be the new standard of care for this population with manageable toxicity. Recall Dara RVD is for transplant eligible patients.

This regimen vs pomalidomie, bortezomib and dexma. 12-month estimated progression-free survival with BPd was 71% compared with 51% with PVd (hazard ratio for disease progression or death, 0.52) Ocular toxicity Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group.

This regimen vs Daratumamab, bortezomib and dexa. Median progression-free survival was 36.6 months in the BVd group and 13.4 in the DVd Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. Again higher ocular toxicity but manageable with dose adjustment and supportive therapy. Those trials may be the come back for Belantamab.

Triplet second line therapy shows superiority over daratumumab bortezomib and dexamethasone. This regimen is now used in first line with lenalidomide in some patients as quadruplet therapy, hence this second line regimen with Blantamab could be a second line option. The eye exam is still a pain and it is also more toxic.