Evaluation of D-Vrd Induction/Consolidation Therapy with MRD-Adapted Maintenance in Transplant-Eligible NDMM Patients with Double-Hit Cytogenetic Abnormality (MMY2094)

Background:

Currently, MM patients with double-hit cytogenetic abnormalities is still an unmet need due to its lack of effective therapies and has poor clinical outcomes overall. In the MASTER study, quadruplet therapy D-KRd demonstrated its efficacy and safety with MRD-adapted approach in the treatment of MM patients (pts), particularly in cyto HR MM pts. Since the phase 3 PERSEUS study DVRd showed promising results in Transplant-eligible newly diagnosed multiple myeloma (TE NDMM) pts and proved the significance of deeper response and longer PFS of D-VRd in induction/consolidation followed by D-R maintenance, it was believed that D-VRd may become standard of care for the treatment of NDMM pts near the future. However, there were no Chinese pts enrolled in the PERSEUS Here we report the preliminary data of the enrollment and the response rate after the induction therapy. (NCT 06158269)

Methods:

40 NDMM patients who are aged 18-70 years and eligible for ASCT are planned for enrollment. They will receive four 28-day cycles of D-VRd followed by ASCT and another four cycles of D-VRd consolidation, followed by MRD-adapted D-VR/R maintenance therapy. Patients will switch to R maintenance if they sustain next-generation MRD negativity for at least 12 months. The primary endpoint is MRD negative rate at the end of maintenance therapy. The secondary endpoints include the duration time of MRD negativity, stringent complete response rate, overall response rate, duration of response, successful mobilization rate, progression free survival and overall survival.

Results: Until 30^th, June, 2024, eight patients were enrolled. All patients had at least two high-risk cytogenetic abnormalities [t(4;14), t(14;16), t(14;20), del(17p), gain/amp (1q), del (1p), or MYC rearrangement]. Three patients had complex karyotype. Median (range) age was 57 (50-68) years. Six patients (75%) were male. Four patients (50.0%) had ISS stage III disease. All patients had R-ISS stage II or III. One patient had strict extramedullary disease. 5 patients had completed four cycles of induction, two patients had undergone ASCT. At a median follow-up of 4.1 months, overall response rate was 100% (≥VGPR 75%, ≥CR 25%) and was gradually improved over the time. One patient with t(4;14), gain(1q), del(17p) and del(13q) early relapsed by the end of induction and exited from the trial. No patients were withdrawn due to adverse effect. The most frequent treatment-emergent adverse events (TEAEs) were neutropenia (50%), thrombocytopenia (25%), diarrhoea (25%). Serious TEAE (intestinal obstruction) only occurred in one patient, leading to treatment delay and quickly recovering in three days.

Conclusion: Based on current study update, D-VRd in TE-NDMM significantly increased depth of response and might improve the outcome of double-hit MM. More pts enrolled with longer follow-up is required in order to have concrete result. The safety profile was consistent with that for Dara IV/SC combined with VRd. These data, together with results from the phase 3 PERSEUS study, demonstrate the consistent and clinically meaningful benefit of quadruplet D-VRd in the treatment of double-hit TE NDMM patients, and provide more evidence in MRD-adapted maintenance approach.

No relevant conflicts of interest to declare.