Treatment Considerations for Newly Diagnosed MM

EP: 1.Case Overview: A 75-Year-Old Man with Multiple Myeloma

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EP: 2.Treatment Considerations for Newly Diagnosed MM

EP: 3.Standard Induction Therapy in Newly Diagnosed MM

EP: 4.Updates from Recent Clinical Trials in Multiple Myeloma

EP: 5.Treatment Options for Relapsed Multiple Myeloma

EP: 6.Unmet Needs and the Future of Multiple Myeloma

Jonathan L. Kaufman, MD: The first thing that we do for the patient with newly diagnosed disease is make the determination: does the patient have symptomatic disease or not? In this case, the patient clearly had symptomatic disease; he had hypercalcemia, lytic bone disease, anemia, and mild kidney renal insufficiency. The next question we ask is: is the patient a candidate for transplant? This patient was not a candidate for transplant; it is primarily based on a combination of age and poor performance status. We have not formally evaluated the patient’s cardiac function, lung function and liver function; however, those are additional things that we would consider whether the patient is a transplant candidate or not. Then once we identify whether the patient is a transplant candidate or not, then we have a series of decisions of what treatment options are available. The other important thing for this patient is he was clearly very symptomatic from myeloma. It's important that we institute a highly effective therapy to not only get control of the myeloma, but to also improve his performance status. When we consider treatments for this patient, we want to consider treatments that not only have good long-term outcomes, but also have very high and rapid response rates.

From a comorbidity standpoint, it's important to understand a patient's underlying cardiac function, liver function and renal function in order to make the best treatment; particularly to help us determine whether the patient is a transplant candidate or not. In a patient who is 79 years old, those patients are not likely going to be transplant candidates. Let's say this patient was 71 or 72 years old; understanding those other comorbidities would really help us make decisions whether the patient was a transplant candidate or not.

When we think about decision making, we do use at age as well as performance status, particularly ECOG [Eastern Cooperative Oncology Group] performance status. When we make decisions, age is probably the least important decision. When we talk about patients in their late 70s/early 80s, those patients are never going to be transplant candidates. We treat them in regimens that are not used in preparation for transplant. More importantly, in making decisions for older patients, is their performance status. In a patient in their early or mid-70s or late 60s where they may or may not be a transplant candidate, it’s really important that understanding what their performance status is. When we think about performance status, I really think about not only the performance status of how their myeloma is making them sick, but what were they like 6 months before the diagnosis of myeloma? When we think about that, especially for our patients between 65 to 80 years old, if their performance status was excellent and their performance status is only limited because of myeloma, I often will treat those patients as transplant candidates; that they will be transplant candidates once we get the myeloma under control. This contrasts with the patient who gets diagnosed, whose has a poor performance status; not because of active myeloma, but because of other comorbidities.

When we think about newly diagnosed disease and making decisions, we have to think about the individual patient; what's the current symptom burden of the patient? What are the kidney functions of the patient? Does the patient have baseline neuropathy that would help make decisions? What's the risk status of the patient? We put all of these questions into the decision-making. The disease characteristics, ie, risk, patient characteristics, ie, comorbidities, and then how the disease is affecting the body. Those are the clinical features; just like in this case where the clinical features are prominent with anemia, hypercalcemia, and painful bone disease.

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