EAA181 - Effective Quadruplet Utilization After Treatment Evaluation (EQUATE): A Randomized Phase 3 Trial for Newly Diagnosed Multiple Myeloma Not Intended for Early Autologous Transplantation

By Shaji Kumar, MD

@myelomaMD

The current standard-of-care frontline therapies for multiple myeloma are triplet combinations such as lenalidomide and dexamethasone with bortezomib (VRd) or daratumumab (DRd). These three-drug regimens are generally effective, and many patients reach minimal residual disease (MRD)-negative status after induction therapy. However, recent studies have shown that combination therapy using all four drug classes may lead to a greater depth of response. Despite this, it is yet unclear if quadruplet therapy likewise leads to improved survival outcomes.

The EAA181 (EQUATE) study is exploring this question for patients who are MRD-positive after induction. The study aims to determine if the addition of bortezomib to consolidation with DRd, followed by daratumumab and lenalidomide (DR) maintenance, results in superior overall survival compared to consolidation with DRd alone followed by DR maintenance.

Amendment #4 is planned to activate soon, and includes numerous important changes to the trial, outlined below

General Protocol Updates:

• The study’s accrual goal has been revised from 1450 to 542 for registration at Step 1 (390 randomized at Step 2)
• Primary and secondary objectives have been revised, and the quality of life endpoints are now exploratory

Eligibility Criteria:

• Step 0 (Pre-Registration):
  • Repeat bone marrow aspirate is not required unless adequate material is not available or disease assessment can only be done by marrow evaluation
  • Clarification of acceptable specimens to submit for eligibility criteria has been added (criterion 3.1.8)
• Step 1 (Registration):
  • Bone marrow biopsy/aspirate is required 28 days or fewer prior to Step 1 registration if measurable disease is only present in bone marrow; otherwise, the biopsy/aspirate must have been performed 90 days or fewer prior
  • Patients who previously received daratumumab for symptomatic myeloma are now eligible
• Step 2 (Randomization): Patients with post-induction MRD-negative or MRD-indeterminate status will go off study; only patients with MRD-positive status will be randomized. Updates have been made throughout the protocol to reflect this change.

Study Plan/Treatment Plans:

• Step 1 (Induction Therapy): If immediate treatment is required, one cycle of treatment is permitted while awaiting results from Adaptive Biotechnologies
• Treatment Plan (All Therapy Phases): Optional lower dosing for patients with certain conditions (i.e., impaired kidney function, age > 75 years) has been added
• Treatment Plan (All Therapy Phases): Patients may be off-treatment for up to 42 days for stem cell collection
• Supportive Care: FDA-approved G-CSF biosimilars may be used
• Measurement of Effect:
  • If any of the required measurements are already met at the time of study entry, then only one repeat measurement is required any time after
  • Response definitions have been updated
• Biological Specimen Submissions: Cycle 4 specimen submissions have been discontinued.

This is not a complete list of all changes to the protocol. Please review the updated protocol carefully for complete details when the amendment activates and is posted to CTSU to avoid protocol deviations. Study resources will be updated to reflect Amendment #4, and once the amendment is active, the resources will be available for download at CTSU.cancer.gov or on the EAA181 Educational Materials page.

Learn more about the EAA181 trial at ecog-acrin.org.

Dr. Kumar (Mayo Clinic) is the study chair for this trial. Michael A. Thompson, MD, PhD, is the study co-chair, Lale Kostakoglu, MD, MPH (NYU Langone Health), is the imaging co-chair, and Matthias Weiss, MD, PhD (Wisconsin NCORP/ThedaCare), is the community co-chair and quality of life co-chair.