IMS 2024 to Serve as Victory Lap for MRD “Success Story”

Experts who study and care for patients with multiple myeloma will travel this week to Rio de Janeiro, Brazil, for the 21st annual meeting of the International Myeloma Society (IMS), taking place September 25-28. Starting days after a key FDA approval for certain newly diagnosed patients, this year’s meeting will celebrate a milestone in the use of minimal residual disease (MRD) negativity in drug development.

IMS logo | Image: International Myeloma Society

“MRD Is an End Point: Our Success Story,” taking place Wednesday, will feature Shaji Kumar, MD, of Mayo Clinic. Kumar’s presentation will outline the landmark unanimous vote in April from the FDA’s Oncology Drugs Advisory Committee (ODAC) to allow MRD negativity to be used as a surrogate end point in accelerated approvals in the US. C. Ola Landgren, MD, PhD, of the University of Miami Miller School of Medicine, who helped present the case to ODAC, will take part in a question-and-answer session.

MRD will be a focal point at Friday’s plenary session, featuring results for the phase 3 CEPHEUS trial (NCT03652064), which compares the anti-CD38 monoclonal antibody daratumumab (Darzelex; Johnson & Johnson) and the standard backbone of bortezomib (Velcade; Millennium/Takeda and Janssen), lenalidomide (Revlimid; Celgene), and dexamethasone (VRd) with VRd alone in patients with multiple myeloma for whom hematopoietic stem cell transplant is not planned as frontline therapy.

In CEPHEUS, the primary end point is the percentage of participants with negative MRD status; progression-free survival (PFS) is a secondary end point.

According to the National Cancer Institute, MRD refers to the presence of a small number of cancer cells in the body after treatment; it is detected through highly sensitive testing that finds a single cancer cell among 1 million normal cells. It is used both as a way to measure the effectiveness of therapies and to help clinicians decide whether a patient must continue or restart therapy. MRD testing can spare patients from taking unnecessary treatments if their disease is in remission, which also helps hold down costs.

From a research standpoint, evidence shows MRD is a reliable predictor of both PFS and overall survival (OS), which means its use as an end point can shave valuable time off regulatory decisions. As treatments in multiple myeloma improve, hitting new benchmarks in PFS and especially OS takes longer; thus, investigators have sought new ways to measure effectiveness.

Saad Usmani, MD, MBA | Image: MSKCC

The CEPHEUS presentation by Saad Z. Usmani, MD, MBA, of Memorial Sloan Kettering Cancer Center, will come a week after the FDA approved the use of a rival combination, anti-CD38 monoclonal antibody isatuximab (Sarclisa; Sanofi) with VRd, for first line treatment of transplant-ineligible patients with multiple myeloma.

Beyond the use of MRD negativity as an end point, CEPHEUS is another trial that raises a question circulating among myeloma experts: do frontline quadruplets offer enough benefit to newly diagnosed patients to consider their use regardless of transplant eligibility?

During a presentation on the isatuximab combination at the American Society of Clinical Oncology in June, Landgren asked whether the lines between “transplant eligible” and “transplant ineligible” are still needed in the era of anti-CD38 therapy.

As the rest of the IMS 2024 agenda shows, getting the most powerful treatments to patients as soon as possible—even before myeloma technically appears—is now the priority.

Technology may offer solutions. Wednesday’s keynote address from Anant Madabhusi, PhD, who is executive director of Emory Empathetic AI for Health Institute in the Winship Cancer Institute, will cover, “AI in Multiple Myeloma: Recent Findings and Opportunities.”

IMS 2024 offers a mix of basic science and drug development updates. Another plenary presentation from Romanos Sklavenitis-Pistofidis, MD, PhD, of Dana-Farber Cancer Institute, is titled, “Single-Cell RNA Sequencing of 6 Million Tumor and Immune Cells in Patients With Plasma Cell Premalignancy Unveils Coregulation of Disease Progression by Tumor Biology and Immune Dysregulation.”

This program will have 6 thematic sessions on Precursor Disease, Newly Diagnosed Multiple Myeloma, High Risk Disease, Relapsed: Treatments Outside of Immunotherapy, Immunotherapy, and Novel Biomarkers—Personalizing Therapy in Myeloma.

On Friday, Kenneth Anderson, MD, and Nikhil Munshi, MD, both of Dana-Farber Cancer Institute, will cochair a collaborative exchange called the “Riney Session,” which will discuss several new potential therapeutic targets.

The keynote, thematic sessions, and the Riney Session are available both in person and in a virtual format, but abstract sessions, which offer both new trial data and updates from previously presented trials, are only available in person or on demand after the conference. Notable abstract presentations will include:

• An MRD update on CASSIOPEIA: daratumumab plus bortezomib/ thalidomide/dexamethasone and daratumumab maintenance in transplant-eligible newly diagnosed multiple myeloma
• PERSEUS cytogenetic risk analysis: daratumumab/bortezomib/ lenalidomide/dexamethasone with daratumumab and lenalidomide maintenance in transplant-eligible newly diagnosed multiple myeloma
• Multiple myeloma progression and evolution of refractory disease explained by integrative multiomics in Moffitt Cancer Center's patient cohort
• Results from the phase 1b TRIMM-2 study: talquetamab plus daratumumab plus pomalidomide in patients with relapsed/refractory multiple myeloma
• Updated phase 1b results from RedirecTT-1 with more than 1 year of follow-up: talquetamab plus teclistamab in patients with relapsed/refractory multiple myeloma
• Phase 3 CARTITUDE-4 study update: OS with ciltacabtagene autoleucel vs standard of care in lenalidomide refractory multiple myeloma
• A comparison of standard of care idecabtagene vicleucel and ciltacabtagene autoleucel chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma