Minimal Residual Disease Detection to Guide Post-Transplant Maintenance Therapy in Multiple Myeloma

Inclusion Criteria

• Males and females >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients with a diagnosis of multiple myeloma who have undergone initial treatment, with or without autologous stem cell transplant, and currently treated with single-agent maintenance therapy (lenalidomide, pomalidomide, bortezomib, daratumumab, or ixazomib) for a duration of at least 1 year. Patients on concomitant corticosteroids for their multiple myeloma are allowed to enroll but must be willing to discontinue corticosteroids if undergoing discontinuation per protocol. The 1 year duration can include time spent receiving at least 8 cycles of doublet or triplet induction regimens OR multi-agent post-transplant maintenance prior to conversion to single agent maintenance therapy
• Patients must either: (1) have had their most recent bone marrow testing within the last 2 years that is negative for MRD by flow cytometry (with a sensitivity of at least 10-5) or by NGS with a sensitivity of at least 10-5 or (2) have ‘unconfirmed complete response (CR)’ defined here as no evidence of a monoclonal protein for at least 2 years but lacking a bone marrow biopsy during that span (bone marrow at screening will serve to establish MRD-negativity in this case)
• Patients must have achieved a complete response (CR) (CR) by International Myeloma Working Group (IMWG) consensus response criteria. For patients with a persistent low level paraprotein (‘M-spike’), mass spectrometry may be used to determine if the paraprotein is significant or not. Results of mass spectrometry may be used to supersede results of serum protein electrophoresis
• It is preferred that patients have a most recent PET/CT within the last 2 years without evidence of myeloma disease. If no PET/CT has been performed within the last 2 years but bone marrow testing reveals no evidence of disease on two consecutive occasions, then the baseline PET/CT on study will suffice. If a PET/CT has been performed in the last 6 months prior to study enrollment, that shall serve as the baseline PET/CT and an additional PET/CT at baseline is not required
• Must have baseline bone marrow sample that can be used for clonality identification for NGS and mass spectrometry if not already performed
• Willing and able to undergo a bone marrow biopsy and aspiration
• Ability to understand and the willingness to sign a written informed consent document
• Females of childbearing potential (FCBP) must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: * If continued on lenalidomide as part of standard of care and * For at least 28 days after discontinuation of lenalidomide
• All participants in the United States (US) must have already been consented to and registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program and be willing and able to comply with the requirements of Revlimid REMS
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the intervention are eligible for this trial

Exclusion Criteria

• Progressive disease as determined per IMWG consensus response criteria
• Have not met the criteria for CR by IMWG consensus response criteria
• MRD-positive disease by flow cytometry, NGS (10^-6), or PCR
• Concomitant hematologic malignancy
• Known or suspected amyloidosis
• Unwilling to undergo a bone marrow biopsy
• Unwilling to discontinue maintenance therapy
• Any clinically significant medical disease or condition that, in the Treating Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent