Is Quadruplet Therapy the New Standard of Care for Patients With Multiple Myeloma?

At the 2024 Great Debates & Updates (GDU) in Hematologic Malignancies meeting in New York, New York, Joseph Mikhael, MD, MEd, FRCPC, FACP, Translational Genomics Research Institute, Phoenix, Arizona, evaluates whether or not quadruplet therapy should be the new standard-of-care treatment for patients with multiple myeloma (MM) who are transplant-eligible versus transplant-ineligible. 

In his discussion, Dr Mikhael highlights the results from the phase 3 PERSEUS, IsKia, and MAIA trials. 

Transcript:

Hi, my name is Dr. Joseph Mikhael. I'm a professor at the Translational Genomics Research Institute in Phoenix, and the Chief Medical Officer of the International Myeloma Foundation.

It's been a privilege to be here at the Great Debates and Updates and Hem[atologic] Malignancies in New York City, and to chair the session in Myeloma. We've had a fantastic day of discussions [on] novel therapies, and of course, debates. 

My specific talk was looking at frontline therapy of multiple myeloma, which, in fact, has gone through a tremendous transformation over the last year as we now have mounting data to provide patients with quadruplet therapy, as they are starting their journey in myeloma, prior to an autologous stem cell transplant.

I summarized the PERSEUS and IsKia trials [which] really are the 2 large phase 3 trials that were designed to answer the question, “Is it better to give 4 drugs versus 3 drugs?” The PERSEUS study evaluated D-VRd, or daratumumab, bortezomib, lenalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone before transplant. We saw in that study a considerable difference in the 4-year progression-free survival in favor of the quadruplet. 

The second study was the IsKia study that looked at isatuximab and other CD30 antibodies now combined with carfilzomib, lenalidomide, and dexamethasone, or KRD, versus KRD alone.

Interestingly, that study had an endpoint of [minimal residual disease] (MRD) negativity and again favored the quadruplet. I concluded that, right now, the standard of care in transplant-eligible patients is to proceed with an autologous stem cell transplant, and prior to that, [give] a quadruplet therapy.

In patients not eligible for transplant, we reviewed the MAIA [trial] data, which we've had for a while, but we know data is about to be released about actually adding to that D-RD backbone or monoclonal antibody immunomodulatory drug backbone by adding now a further agent. The data with isatuximab, bortezomib, lenalidomide, and dexamethasone is soon to be released in transplant-ineligible patients. So, really the bottom line is that we're going to be giving quadruplet therapies using multiple mechanisms of action in likely all if not nearly all patients with a newly diagnosed multiple myeloma.

Lastly, I spent a little bit of time talking about the importance of optimizing the drugs that we have. It's so important to use the drugs we have carefully and appropriately, and I focused a little bit on dexamethasone [and] introduced my hashtag #DownWithDex because I think we use too much dexamethasone, and it's better for patients to introduce at the appropriate dose, be it 20 or 40 milligrams for approximately 2 to 3 months, and then taper it down to discontinue it by 6 months. That strategy optimizes the benefit of dexamethasone without the complication that we see of so many of the side effects thereafter.

So, although there's all this excitement about relapsed myeloma, there's a lot going on in frontline therapy as well.

Source: 

Mikhael J. Multiple Myeloma: Strategies to Optimize Frontline Treatment Selection. Presented at the 2024 Great Debates & Updates in Hematological Malignancies: April 5-6, 2024. New York City, NY.