Examining CD38-Targeting Antibody Therapies for Patients With Newly Diagnosed Transplant-Ineligible Multiple Myeloma

At the 2023 Great Debates & Updates in Hematologic Malignancies meeting in Boston, Massachusetts, Peter Voorhees, MD, Atrium Health Levine Cancer Institute, Charlotte, North Carolina, shares data from the MAIA study on the use of CD38-targeting antibodies among patients with newly diagnosed transplant-ineligible or transplant-deferred multiple myeloma.

Transcript: 

My name is Peter Voorhees and I'm the chief of the plasma cell disorders division at Levine Cancer Institute, Atrium Health in Charlotte, North Carolina. I'm here at the Great Debates and Updates [in Hematologic Malignancies meeting] in Boston, Massachusetts. 

Today, I was discussing optimal frontline therapy for newly diagnosed [multiple] myeloma (MM) patients. When we focus on those patients who are not eligible for transplant or for those who defer transplant, there's really a lot of interest emerging in the use of CD38 antibodies, in this particular space.

The MAIA study was a revolutionary study that looked at daratumumab [a CD38-targeting antibody] in the lenalidomide-dexamethasone backbone for patients with newly diagnosed myeloma. What that study showed is [that] not only did the addition of daratumumab improve depth of response, whether you measure that by complete response or achievement of [minimal residual disease] (MRD) negativity, but it improved progression-free survival.

When you look 5 years out for those patients that had been assigned to daratumumab, lenalidomide, and dexamethasone, the progression-free survival was 52.5%, which is the longest that has ever been seen in a randomized study in a non-transplant setting. More importantly, they saw an overall survival advantage. So, the addition of daratumumab to the len[alidomide]-dex[amethasone] backbone improved overall survival for those patients.

There [are] a lot of questions about whether dara[tumumab]-len[alidomide]-dex[amethasone] is better than bortezomib-len[alidomide]-dex[amethasone] (RVD) for this group of patients. We know that RVD is a standard of care regimen for this group of patients as well based [on] the [Southwest Oncology Group] (SWOG) S0777 study.

There was an interesting presentation at [the American Society of Clinical Oncology meeting] (ASCO) this year that took patients in those 2 studies who were 65 years of age and older. They matched them by performance status, [lactate dehydrogenase] (LDH), [International Staging System] (ISS) stage, [and] by standard versus high-risk cytogenetics. There did appear to be a progression-free survival advantage with dara[tumumab]-len[alidomide]-dex[amethasone] over len[alidomide]-bortezomib-dex[amethasone]. 

Now, this is an indirect comparison, so you have to take that data with a significant grain of salt. The SWOG group is currently undertaking a study in non-transplant patients comparing RVD to dara[tumumab]-len[alidomide]-dex[amethasone] in the upfront setting. That study will more definitively establish which is the best choice going forward.

Perhaps even more interesting is whether or not we can use quadruplet therapy in this patient population, like we've started to do in our more fit transplant-eligible patients. There are 2 phase 3 studies, CEPHEUS and IMROZ, which [look] at RVD with or without either daratumumab or the other CD38 antibody, isatuximab, in this group of patients. We'll see if we'll be able to improve even further on the results from MAIA.

Source:

Voorhees, P. Optimal Frontline Therapy of Myeloma. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; August 17-19, 2023; Boston, Massachusetts.