Standard Induction Therapy in Newly Diagnosed MM
Key opinion leader in hematology Jonathan L. Kaufman, MD, discusses standard treatment options for newly diagnosed multiple myeloma in transplant and nontransplant treatment settings.
Jonathan L. Kaufman, MD: There are currently standard treatments for induction in newly diagnosed symptomatic myeloma patients. When we make our decisions about the standard treatment for newly diagnosed myeloma, the first thing that we do is determine whether the patient is or is not a transplant candidate. If the patient is not a transplant candidate, here in the United States, there are typically 2 regimens that are considered standard. One is the combination of bortezomib, lenalidomide, and Dexamethasone, otherwise known as RVd.RVd was studied in a nontransplant setting; both transplant and nontransplant candidates were used and it was compared to the combination of lenalidomide and dexamethasone. There was clearly a benefit of the 3-drug RVd over RD [lenalidomide and dexamethasone] in terms of response rate, progression-free survival and overall survival. For the nontransplant candidate, RVd will likely be modified to what we know as something like RVd light; lenalidomide is dose reduced, Dexamethasone is dose reduced and bortezomib is given once a week versus twice a week. The other common regimen used now in patients with newly diagnosed myeloma who are not transplant candidates, is the combination of daratumumab, lenalidomide and Dexamethasone, otherwise known as DRD. This was studied in the MAIA study that compare DRD versus RD for newly diagnosed nontransplant candidates. There was a clear benefit both from response rate, as well as progression-free survival in the patients for the 3 drug arm versus the 2 drug arm. We have not seen survival data yet for this regimen; I presume that we’ll see it whether it’s positive or negative over the years to come. The other thing that has changed over the past year with the advent of subcutaneous daratumumab; this is a very convenient regimen for patients. In the context of the pandemic despite having to come into the infusion center for daratumumab due to it being subcutaneous dosing, they would have to come in for a relatively short period of time. That has been a very important treatment for my nontransplant eligible patients in the context of the COVID-19 pandemic. For patients who are younger and are transplant candidates, there are now several standards of care. RVd remains the standard of care; it has shown a very high response rate and a very good regimen as induction. KRd has been studied; the combination of carfilzomib, lenalidomide, dexamethasone was compared against RVd in a study. In this group of patients where they weren’t high risk there was no difference in outcomes. We’ve seen recent data that KRd with transplant followed by either KR or our maintenance was very effective, including in high-risk patients. We’re now starting to see 4 drug therapy, the addition of daratumumab plus RVd as well as the addition of daratumumab plus KRd. In addition to daratumumab, we’ve seen 3 drug backbone regimens like KRd with Isatuximab and the second anti-CD38 antibody approved for myeloma approved in the relapse setting.
Transcript edited for clarity.
Case: A 75-Year-Old Man with Multiple Myeloma
Initial Presentation
- A 75-year-old man presents with worsening fatigue on exertion, pallor, and hip pain
- PMH: osteoarthritis
- PE: tired appearing male, poor hand-grip strength, mild tenderness on palpation of the left hip
- ECOG 2
Clinical workup
- Hb 9.8 g/dL, corrected calcium 11.9mg/dL, LDH 295U/L, creatinine 1.4mg/dL, albumin 3.7g/dL, CrCl 50mL/min
- Peripheral blood smear showed rouleaux formation
- Beta-2 microgloblulin 5.1 mcg/mL, M-protein 2.2 g/dL
- Lambda free light chains: 0.6 mg/dL, kappa free light chains: 14.3 mg/dL, ratio: 29 (k/l)
- FISH: hyperdiploid
- UPEP: M-spike of 400 mg of lambda light chains in 24 hours
- PET/CT revealed lytic bone lesions in the left hip
- Bone marrow biopsy shows 58% plasma cells IgG k
- Diagnosis: ISS and R-ISS, standard risk, stage II MM
Treatment
- Patient is ineligible for ASCT due to comorbidities
- Initiated treatment with daratumumab + bortezomib + melphalan + prednisone
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