Page 41 - Haematologica Vol. 109 - July 2024

REVIEW ARTICLE - Minimal residual disease in multiple myeloma R. Szalat et al. Table 3. Ongoing prospective clinical trials evaluating minimal residual disease-adapted therapy.
Clinical trial
Patient population
Treatment scheme
UMCC 2018.056 (NCT04140162)
Phase II study with MRD-driven adaptive strategy in treatment for newly diagnosed MM with upfront daratumumab-based therapy
This phase II trial will test whether the combination of DaraRd as induction therapy, followed by DRVd consolidation therapy, if needed, will result in more patients achieving MRD-negative status, relative to the standard of care. Consolidation therapy will be administered only to those patients with MRD-positive status after induction therapy.
MIDAS (NCT04934475)
Phase III clinical trials in newly diagnosed MM patients
IFM 2020-02 will enroll patients eligible for ASCT aged <66 years. All patients will receive induction based on 6 cycles (28-day) of Isa-KRd, in order to achieve deep responses and high MRD negativity rates. Patients will be classified at diagnosis according to cytogenetics (standard vs. high-risk cytogenetics defined by the LP score including 17p deletion, t(4;14), del(1p32), gain 1q, trisomy 21 and trisomy 5.
PERSEUS (NCT03710603)
Phase III clinical trial daratumumab, VELCADE (bortezomib), lenalidomide and dexamethasone compared to VELCADE, lenalidomide and dexamethasone in subjects with previously untreated MM
A phase II study comparing D-VRd vs. VRd in subjects with previously untreated multiple myeloma who are eligible for high-dose therapy. MRD- negative subjects will stop daratumumab after sustained MRD negativity for 12 months and after a min. of 24 months of maintenance. Daratumumab should be restarted at recurrence of MRD or confirmed loss of CR without disease progression.
DRAMMATIC (NCT04071457)
Phase III clinical trial lenalidomide +/- daratumumab/rHuPh20 as post-ASCT maintenance for MM w/MRD to direct therapy duration (DRAMMATIC)
In this trial, patients who received HDC-SCT are randomized between lenalidomide for 2 years and lenalidomide + daratumumab. After 2 years of maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized to either continue or discontinue the assigned treatment.
EMN20 (NCT04096066)
Phase III clinical trial. A trial that compares two treatments in newly diagnosed myeloma patients not eligible for transplant (KRd vs. Rd)
This protocol is a randomized, multicenter study designed to determine the MRD negativity and the PFS of KRd treatment regimen. Patients will be randomized in a 1:1 ratio to receive KRd (Arm A) or Rd (Arm B). Patients will be stratified basing on ISS and fitness status using a web-based procedure completely concealed to study participants. Patients will be treated until disease progression or intolerance to the therapy. The only exception is for patients enrolled in KRd arm who achieve at least a VGPR during the 1st year of treatment and in sustained MRD negativity (MRD negative at least at 10-5 after 1 and 2 years of therapy): these patients will stop carfilzomib administration after 2 years, whereas treatment with lenalidomide and dexamethasone will be continued.
MASTER-2 (NCT05231629)
Phase II clinical trial. Sequential therapy in MM guided by MRD assessments (MASTER-2)
This research study will determine the proportion of patients with lowest MRD response obtainable after receiving 6 cycles of study treatment. MRD is MM cells below the level of 1 cancer cell out of 100,000 in the BM. For patients who become MRD ‘negative’ (i.e. less than 1 cancer cell out of 100,000) at the end of 6 cycles of therapy, this study will evaluate if that good response can be maintained with 3 additional cycles of treatment instead of use of ASCT. For patients who are MRD ‘positive’ at the end of 6 cycles of therapy, this study will answer whether more patients can become and remain MRD ‘negative’ with ASCT plus teclistamab in combination with daratumumab when compared with patients who undergo ASCT followed by lenalidomide plus daratumumab.
RADAR (EudraCT 2019-001258-25)
Phase III clinical trial. Risk-adapted therapy directed according to response comparing treatment escalation and de-escalation strategies in NDMM suitable for stem cell transplant
All participants will receive the same initial induction treatment and during this time will have genetic tests to determine whether they have ‘standard- risk’ or ‘high-risk’ disease. Following this chemotherapy treatment participants will receive ASCT. After induction treatment participants will be allocated to a second stage treatment group based on their genetic risk, high-risk or standard-risk, and on how well the myeloma has responded to the initial treatment. Each treatment group will then receive different combinations of medication to investigate their benefit. Treatment will comprise of combinations of isatuximab, bortezomib, cyclophosphamide, lenalidomide and dexamethasone.
ASCT: autologous stem cell transplanation; BM: bone marrow; CR: complete remission; DaraRd: daratumumab + lenalidomide + dexametha- sone; DRVd: daratumumab + lenalidomide + bortezomib + dexamethasone; D-Vrd: daratumumab, VELCADE (bortezomib), lenalidomide, and dexamethasone; HDC: high-dose chemotherapy; IFM: Intergroupe Francophone du Myélome; Isa-KRd: KRd-isatuximab; ISS: International Staging System; KRd: carfilzomib, lenalidomide and dexamethasone; MIDAS: Minimal Residual Disease Adapted Strategy; NDMM: newly diag- nosed patients with multiple myeloma (MM); PFS: progression-free survival; Rd: lenalidomide-dexamethasone; Vrd: VELCADE, lenalidomide, and dexamethasone; VGPR: very good partial response.
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