Yvonne Efebera, MD: That brings us to the newly diagnosed. What are the triggers to initiate treatment? The CRAB [calcium elevated, renal insufficiency, anemia, bone lesions] has been mentioned before, are the symptoms, the myeloma-defining event. Initially, we label these patients with smoldering myeloma if they have a bone marrow biopsy showing a plasma cell percentage of 60% or the involved/uninvolved free light chain ratio of 100 mg/L and above.
We used to say these are patients with smoldering myeloma, let’s just watch them. Now these are true myeloma cases and starting treatment, even when they are asymptomatic, is beneficial. That includes the PET [positron emission tomography] and MRI scan that are part of initial testing. The skeletal survey and now PET, MRI, or CT scans can be used as initial assessment to see if they have 1 or more involved lesions, 5 mm or above. Those are the patients for whom you will start treatment.
Thomas Martin, MD: When we see a patient who has newly diagnosed myeloma, we basically are assessing how well they’ll be able to tolerate whatever induction therapy we can administer. We try to assess the best regimen at that point. The first thing that comes into our mind is, is this person a transplant candidate or not? A lot of that has to do with their cardiovascular health. As long as they don’t have any significant cardiac comorbidities or pulmonary comorbidities or are not on any oxygen, then most patients—if they’re fit and they’re able to do all their activities of daily living and some exercise—are likely going to be a transplant candidate.
We recently published some ASCO [American Society of Clinical Oncology] guidelines with the premise that age is typically not a determinant of whether we’re going to take patients to transplant. That said, I don’t know what you do, Yvonne, but for us at UCSF [University of California, San Francisco], we typically look for patients less than age 75. There is the rare patient age 75 to 80 who might be fit enough to go to transplant. But the majority of patients are less than age 75, and honestly the majority are less than age 70.
For some patients who are older and have comorbidities like neuropathy, we might want to avoid agents that cause neuropathy. For some patients who have cardiac dysfunction or have congestive heart failure, we likely will go low on the steroids, less dexamethasone, and will have less problem with arrhythmias and with water gain. In some patients who have renal failure, we often have to adjust the doses of the medication. Sometimes a lenalidomide-containing regimen may not be our first choice for somebody with renal insufficient, and we may choose something like bortezomib/cyclophosphamide, and dexamethasone.
You already described very well the molecular risk status, and I agree that we tend to be very aggressive with the treatment of high-risk patients. We usually don’t have those data back when we initiate somebody with therapy. If we do, in somebody who has high-risk disease, typically it’s an immunomodulatory drug [IMid] plus a proteasome inhibitor [PI] plus a steroid, at least a triplet for people who have higher-risk disease. The stage in my mind doesn’t matter so much in terms of what therapy we’re going to do right out of the gate. But I do think we have to make a decision right out of the gate on whether we’re using a PI plus an IMiD, a PI plus cyclophosphamide, and then which PI are we going to use: bortezomib or carfilzomib.
I’m curious, Yvonne, to see what your favorite regimen is in pretransplant patients and in nontransplant patients. For me, in the pretransplant patients I’m still a fan of KRd [carfilzomib, lenalidomide, dexamethasone], trying to do 4 cycles of KRd as a pretransplant. That’s been my go-to, and that’s what I do. In the older population, the nontransplant eligible, I think almost everybody can get lenalidomide, bortezomib, and dexamethasone. But lately I’ve actually been giving a monoclonal antibody. I’ve been more interesting in giving daratumumab [DARA] with lenalidomide and dexamethasone, because I think it’s extremely well tolerated. How about you, Yvonne?
Yvonne Efebera, MD: Yes. We’ll come back to the timing of transplant, but for the induction regimen, I’m still a fan of bortezomib, lenalidomide, dexamethasone. And of course, in high-risk patients, maybe adding DARA/bortezomib, DARA to the triplet regimen based on the GRIFFIN trial.
Transcript Edited for Clarity