Expert hematologist-oncologist Ajay K. Nooka, MD, MPH, FACP, shares his perspective on the management of a woman newly diagnosed with multiple myeloma.
Ajay K. Nooka, MD, MPH, FACP: Hello, andwelcome to this Targeted Oncology program: The Evolving Treatment Landscape of Newly Diagnosed Multiple Myeloma.
I’m Ajay Nooka, associate professor of the Department of Hematology and Oncology and the director of the Myeloma Program at the Emory University School of Medicine in Atlanta, Georgia.
Today, I’m going to discuss a number of updates in the treatment of newly diagnosed multiple myeloma. I’ll present the case and discuss my treatment approach to the case to illustrate how I apply the recent evidence to clinical practice.
I’ll present the case of a 54-year-old woman with multiple myeloma. She has presented with a revised international staging system [R-ISS], stage 2 disease at presenting labs, with a hemoglobin of 7, [and] a beta 2 microgram of 6 milligrams per deciliter. [The] abdomen of 3.2 grams per deciliter, qualifying heart for [an ISS [international staging system] stage 3 disease, to calcium levels for 11.3 milligrams per deciliter. LDH [Lactate dehydrogenase] was within normal limits per institutional standards at 200 units per liter.
She had a creatinine clearance of 45 milliliters per minute. A bone marrow biopsy was done showing normal cellular bone marrow. She had 22% [of] chrono plasma cells.
There was no cytogenetic abnormality seen by conventional metaphase carriers. There were no cytogenetic abnormalities that were seen by metaphase cytogenetics or any fissure abnormalities that were found.
She had an ECOG performance status of a 1. Her tumor burden, when we look at the free light chain, was 24 milligrams per deciliter or equal to 240 milligrams per liter. Please watch out for the units, and serum IgG of 5 grams per deciliter.
She had a PET [positron emission tomography]/CT done as a part of the initial staging workup, which showed multiple bone lesions, both in the axial and appendicular skeleton.
She did not have any extra modular disease. She was diagnosed with R-ISS stage II, ISS stage III disease, IgG kappa multiple myeloma, and she’s identified as a transplant-eligible patient, often to have minimal commodities and younger age.
She underwent induction therapy with daratumumab [Darzalex], bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone— the DVRd treatment—and [the] patient achieved a VGPR [very good partial response] post-induction therapy.
She underwent a stem cell mobilization, and 2 weeks later she underwent a stem cell transplant with melphalan 200 mg/m2. She achieved a VGPR post-transplant, and now she’s here for discussion.
This is a young patient and I correctly agree with the choice of the induction treatment for a younger patient like this. So historically we have used a 3-drug regimen—lenalidomide, bortezomib, and dexamethasone. We knew the 3-drug regimen would result in a much better depth of responses compared to the 2-drug regimens.
So it went without saying the 3-drug regimens have become the backbone or the standard of care regimens across the country. Now, [the] addition of a fourth drug to get the depth of response has been evaluated in multiple trials.
What was very unique about the choice of daratumumab to be combined with this 3-drug regimen is the overlap in toxicities at minimal. And yet, we are able to see the depth of responses and the benefit of this addition of the fourth agent, which led to us easily translating our practices into using these quadruple regimens, at least in the younger patients, to make sure that we attain those depths of responses if they’re looking prior to a transplant.
This patient did receive a 4-drug regimen. She’s young, [and] has minimal comorbidities. And I completely agree with the choice of the induction treatment for this patient.
I typically choose to use a quadruplet regimen for a younger patient with minimal comorbidities. If there is any concern for me that the fourth agent could be too toxic for a patient, then the choice of the 3 drugs comes in.
So, as we alluded to before, in terms of our evolution from the 3-drug to the 4-drug treatments, we want the benefits of these treatments, not the toxicities of these treatments. So if there’s a patient that is eligible to receive these 4 drugs, my choice would always be a 4-drug regimen.
We have seen it time and again, the depth of induction, the depth of response, [and] post-induction therapy matters a lot in the long run. What you achieve in terms of the first 3 or 4 months of treatment, the choice of the treatment that you make, has an impact in the long run.
It’s extremely essential for me to use the most effective treatment in that time setting, in the first 3 or 4 months of the treatment, for the patient. And here in this specific patient, there is no reason for me to use a 3-drug regimen as the data is piling up, more and more data that we get, showing that the benefit of 4 drugs is much better than the 3-drug regimens.
And again, we have to understand what is the fourth drug in this mix that we are looking for? And the fourth drug here is a CD38 monoclonal antibody, and we are having more and more data. And as the data matures, we are seeing the PFS [progression-free survival] benefits all favoring the 4-drug regimen.
And clearly, deeper responses are seen with these 3 regimens, and these are resulting in MRD [minimal residual disease] negative states, [and] PFS benefits. We don’t see any overall survival benefits at this point because the follow-up is too short at this point.
Transcript edited for clarity.