Evolving Frontline Therapies for Patients With Newly Diagnosed Multiple Myeloma

Peter Voorhees, MD, Atrium Health Levine Cancer Institute, Charlotte, North Carolina,  discusses evolving frontline therapies for patients with newly diagnosed multiple myeloma, focusing on the use of quadruplet-based induction therapy among patients who were fit for upfront transplants, which he presented at the 2023 Great Debates & Updates in Hematologic Malignancies meeting. 

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 discussed the evolving field of upfront therapy for newly-diagnosed multiple myeloma patients. Initially, [I] focused on patients who are more fit and potentially eligible for upfront transplant. I spent a fair amount of time discussing the evolving role of quadruplet-based induction therapy for that group of patients, specifically, the addition of the CD38 antibodies to the lenalidomide proteasome inhibitor, dexamethasone, a backbone for that group of patients. 

It was the CASSIOPEIA trial that looked at daratumumab, bortezomib, thalidomide, and dexamethasone in that particular context. That was the first study to demonstrate an improvement in progression-free survival with a quadruplet over a triplet in a transplant-eligible patient population.

In the Alliance Myeloma Committee, we conducted a study called GRIFFIN, which was a randomized phase 2 study that looked at lenalidomide, bortezomib, and dexamethasone (RVD) with or without daratumumab in upfront transplanted patients. What we showed there too, just like in CASSIOPEIA, depth of response was improved when daratumumab was added to the RVD backbone, both when you look at it by complete response rates as well as minimal residual disease negativity. With longer follow-up, that translated into an improvement in progression-free survival. 

There is also very interesting data emerging on the use of daratumumab with carfilzomib, lenalidomide, and dexamethasone. Dr. Landgren [C. Ola Landgren, MD, PhD, Sylvester Comprehensive Cancer Center], who's here in Boston with us, spearheaded the MANHATTAN study that looked at this regimen in newly-diagnosed myeloma patients, and Luciano Costa, [MD], at [the] University of Alabama at Birmingham had a very innovative study looking at a [daratumumab, carfilzomib, lenalidomide, and dexamethasone] (Dara-KRd) platform in the context of stem cell transplant.

Dara-KRd-based induction therapy is leading to [an] unprecedented depth of response with regard to [minimal residual disease] (MRD) negativity. I think one of the important take-home points as we use these quadruplets more in newly-diagnosed myeloma patients, [is] that we need to be cognizant of the impact that a CD38-antibody has when you add it to lenalidomide-based therapy and the impact that that has on stem cell mobilization. 

I always strongly encourage those in the community treating patients with newly-diagnosed myeloma with these regimens to get them to the transplant centers very early in their course so they can get their foot in the door and ensure that they're getting stem cells collected and mobilized after anywhere from 12 to 16 weeks of therapy and ideally, not beyond that point, where the risk of stem cell mobilization failure starts to increase. 

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.