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.
We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) using data from 4 phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD negativity rates and reduced the risk of disease progression or death by approximately half vs standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response or better (≥CR) with MRD-negative status and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10−5 sensitivity threshold). Patient-level data were pooled from all 4 studies and for patients with TIE NDMM and patients with RRMM who received ≤2 prior lines of therapy (≤2 PL). PFS was evaluated by response and MRD status. Median follow-up (months) was 54.8 for POLLUX, 50.2 for CASTOR, 40.1 for ALCYONE, and 36.4 for MAIA. Patients who achieved ≥CR and MRD negativity had improved PFS vs those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P < .0001; TIE NDMM and RRMM ≤2 PL HR 0.20, P < .0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that ≥CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching ≥CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support ≥CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM. These trials were registered at www.clinicaltrials.gov as #NCT02076009, #NCT02136134, #NCT02195479, and #NCT02252172.
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.
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