P-171: DARATUMUMAB AS CONSOLIDATION THERAPY IN MULTIPLE MYELOMA PATIENTS IN >VGPR/MRD POSITIVE AFTER FIRST LINE THERAPY: FINAL ANALYSIS OF THE MULTICENTRIC PHASE 2 STUDY DART4MM

Introduction:
Although multiple myeloma patients experienced progresses in survivals the disease is still incurable. Novel drugs give deeper responses respect to the past, CR is not sufficient to testify durable response. MRD status measured both by NGF or NGS is a consolidated prognostic parameter in MM trials. A consolidation therapy after ASCT has been reported to increase the level of MRD responses. Daratumumab, IgG/k monoclonal antibody anti-CD38, is now the standard of care therapy. However, trials are ongoing to show Daratumumab efficacy as consolidation/maintanance therapy after a first line of therapy and MM eradication potential as means of MRD negativity, especially if used in a very good responder group of patients after ASCT.

Methods:
Bone marrow aspirates from MM patients, achieving >VGPR after a fixed first line of therapy were collected from 5 centers for MRD positivity. NGF was centralized at the Hematology University of Siena,measured according to Euro Flow guidelines with 2 height colors tubes. MRD detection was set at 10^-6 in all samples analyzed. Clinical and biological data as well as molecular cytogenetics information was collected. PET/CT at screening and every 6 months; ISS status and presence of high-risk features by FISH. Daratumumab was given according to monotherapy schedule weekly for 8 times and then every two weeks for 8 times. Primary endpoint was set at 6 months: MRD neg patients stopped the drug,MRD pos patients continued once a month until 24 months. MRD was measured at 2 ,6,12,18,24 months (MRD2, 6,12,18,24). PFS and OS were measured and analyzed related to MRD status, FISH risk, ISS.

Results:
Between December 2018 and March 2022 , 110 MM patients were screened and 50 were enrolled. Median age was 61 (range 40-77); ISS 3 was present in 16% of the patients. High risk cytogenetics in 9/50(18%) patients. 45 patients received an ASCT( 1 ASCT 34; 2 ASCT 11) and 5 patients after VMP treatment. Seventeen (34%) patients were judged in CR and 33 (66%) in VGPR at the enrollment. At the primary endpoint 15/50 (30%) patients were MRD negative. Interestingly other 8 patients became MRD negative for the first time after 6 months and during darat therapy between month 6 and 24 and 2 patients had a MRD neg detection at month 2 but unsustained later. Totally 27/50 (54%) MM patients had at least one MRD neg detection. At a median follow up of 41 months (range, 26-65), 23 (46%) patients relapsed (15 before 24 months). Median PFS and OS are not reached. In particular achieving at least one MRD negativity is statistically significant vs not reaching MRD negativity (NR vs 24 months, p=0,001). Particularly, MRD6 negativity is not significant (44 vs 39 months, p=0,44) but MRD12 it is (NR vs 49 months, p=o,0001).

Conclusions: Dara is efficacious as consolidation/eradication therapy given 6 to 24 months in multiple myeloma patients already achieving >VGPR but MRD pos by NGF. About a third of patients do achieve long term MRD neg status.