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GEM-CESAR Trial Overview


Saad Usmani, MD, MBA, FACP, reviews the GEM-CESAR trial data presented at ASH 2022 on a potential curative strategy for high-risk smoldering myeloma and discusses his treatment strategy for this disease.

Saad Usmani, MD, MBA, FACP: The GEM-CESAR trial has been previously reported; this is a longer follow-up. The study was reported about 3 years ago, and the initial report looked at the response rates and early MRD [minimal residual disease] negativity rates. This is a trial that looked at 90 patients with smoldering myeloma at high risk of progression. It was led by the Spanish Myeloma Group to see if they can potentially “cure” some patients with smoldering myeloma by employing an aggressive approach where KRd [carfilzomib, lenalidomide, dexamethasone] was utilized as induction, then patients were given an autologous stem cell transplant, followed by 2 cycles of KRd as consolidation, followed by len [lenalidomide] and dexamethasone as maintenance treatment.

The primary end point was MRD negativity after transplantation, and then at 3 and 5 years. This study was affected by the [COVID-19] pandemic. MRD evaluations at the 3-year mark were done in a lower proportion of patients. Nevertheless, they have a follow-up of about 6.5 years on this study, and they were reporting data. So 94% of the patients in this trial were alive and progression free. Six patients had progressed to multiple myeloma, and 7 patients had died. Then of the 90-odd patients, 31 patients had biochemical progression, or conversion from MRD negative to MRD positive. The biologic PFS [progression-free survival] for those patients at 5 years was 72%. The study reported a high proportion of patients in the study who were MRD negative 4 years after the autologous stem cell transplantation. They’re making the case that if you can get patients into sustained MRD negativity, that should be the key to potential curative strategies in this patient population.

Our approach to smoldering myeloma is first to prognosticate whether patients are at a high risk of moving toward active myeloma requiring treatment. We typically utilize the 20/2/20 International Myeloma Working Group criteria, which looks at whether patients have a 20% or more plasmacytosis on the bone marrow biopsy, 2 or more grams of M-spike, or an involved/uninvolved light chain ratio of 20 or more. If patients are deemed to have high-risk smoldering myeloma, we tend to offer them clinical trials for that particular indication because we haven’t figured out the right way of treating or intervening in this patient population yet. The ECOG trial led by Sagar Lonial [MD, FACP,] did show that lenalidomide as a single agent can delay that progression to active multiple myeloma, and it speaks to perhaps an immunomodulatory approach in certain high-risk smoldering myeloma subsets that can be employed.

The key question is, if we are intervening in this patient population, what is the objective? We talked about this curative strategy, and then there is the controlled strategy. We still need to figure out, there is no standard of care approach for this patient population. We’d still like to observe patients on clinical trials rather than providing intervention to all patients within this category. I have to say, for older patients who have high-risk smoldering myeloma, I favor having that discussion about single-agent lenalidomide.

Transcript edited for clarity.

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