Dr Landgren on the Utility of MRD as an End Point in Multiple Myeloma Trials

C. Ola Landgren, MD, PhD, professor, medicine, Department of Medicine, chief, Division of Myeloma, Department of Medicine, co-leader, Translational and Clinical Oncology Program, Paul J. DiMare Endowed Chair in Immunotherapy, director, Sylvester Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Universtiy of Miami Health System, discusses the utility of minimal residual disease (MRD) as an end point in clinical trials evaluating treatments for patients with multiple myeloma.

In April 2024, the FDA’s Oncologic Drugs Advisory Committee voted that available data 

the use of MRD as an end point for accelerated approval

 of new treatments for patients with multiple myeloma, marking an advance in addressing unmet needs within this patient population, Landgren begins. There is a strong demand for an early clinical trial end point that is reasonably likely to predict long-term clinical benefit of agents in patients with multiple myeloma, as there is not yet a cure for this disease, Landgren says. This need prompted Landgren and colleagues to develop a meta-analysis that was designed based on FDA guidance for considering MRD as a clinical end point and a potential basis for accelerated approval, he explains.

Having an early end point that is likely to predict clinical benefit could revolutionize drug development, he expands. Instead of enrolling patients in a clinical trial for 2 years and waiting an additional 10 years for data maturation, a large trial could enroll patients for 2 years, check MRD status after 1 year, and obtain results much faster, Landgren says. If the trial is successful, the drug could be reviewed and approved swiftly, allowing it to reach patients much sooner, he elucidates.

This approach could reduce the wait time for certain agents from 12 years to just 3 years for newly diagnosed patients, expediting access to effective drugs, Landgren continues. In multiple myeloma, where the clinical unmet need is significant and curative treatments are still unavailable, using MRD as an end point presents an opportunity to develop potentially curative therapies, Landgren emphasizes. This shift is crucial for providing patients with faster access to life-saving medications, he concludes.

Videos

C. Ola Landgren, MD, PhD, discusses the utility of minimal residual disease as an end point in clinical trials for the treatment of multiple myeloma.

Experts in multiple myeloma discuss third-line and subsequent options for treating multiple myeloma, and BCMA-targeted approaches presented at the ASH 2020 Virtual Meeting.

Data from the following presentations are discussed:

CARTITUDE-1: Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen–Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma. (Madduri, ASH 2020 Abstract 177)

Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes. (Alsina, ASH 2020 Abstract130)

Universal: An Allogeneic First-in-Human Study of the Anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in Relapsed/Refractory Multiple Myeloma. (Mailankody, ASH 2020 Abstract129)

Third and Subsequent Line Options for Multiple Myeloma

Important considerations regarding the sequencing of IMid–versus–PI-based approaches for relapsed/refractory multiple myeloma based on updates presented at the ASH 2020 Virtual Meeting.

Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Efficacy and Safety Results of the Phase 3 CANDOR study. (Dimopoulos, ASH 2020 Abstract 2325)

Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis of the Phase 3 CANDOR Study in Patients With Early or Late Relapse. (Weisel, ASH 2020 Abstract 2287)

Evaluation of Minimal Residual Disease (MRD) Negativity in Patients With Relapsed or Refractory Multiple Myeloma Treated in the CANDOR Study. (Landgren, ASH 2020 Abstract 2282)

Isatuxumab Plus Carfilzomib and Dexamethasone vs Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma (IKEMA): Interim Analysis of a Phase 3, Randomized, Open-label Study. (Moreau, ASH 2020 Abstract 2316)

APOLLO: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM). (Dimopoulos, ASH 2020 Abstract 412)

A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide With or Without Pomalidomide in Patients with Relapsed and Refractory Multiple Myeloma. (Sebag, ASH 2020, Abstract 413)

Updates in Relapsed/Refractory Myeloma

Insight regarding updates in the frontline setting for patients with multiple myeloma, including quad versus triplet regimens, the use of weekly carfilzomib, lenalidomide, dexamethasone, and daratumumab, and transplant in newly diagnosed multiple myeloma.

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy. (Kaufman, ASH 2020, Abstract549)

Weekly Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab (wKRd-D) Combination Therapy in Newly Diagnosed Multiple Myeloma: Final Results from a Clinical and Correlative Phase 2 Study. (Landgren, ASH 2020 Abstract 3204)

Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow-up Analysis of the IFM 2009 Trial. (Perrot, ASH 2020 Abstract 143)

Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in the Randomized Forte Trial. (Gay, ASH 2020 Abstract141)

Ola Landgren, MD, PhD, Sylvester Comprehensive Cancer Center

Articles

Dr Landgren on the Utility of MRD as an End Point in Multiple Myeloma Trials

Third and Subsequent Line Options for Multiple Myeloma

Updates in Relapsed/Refractory Myeloma

Updates in Multiple Myeloma in the Frontline Setting