Case Overview: 79-Year-Old Woman With Multiple Myeloma

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Clifton C. Mo, MD: Hello everyone. My name is Clifton Mo, and I’m a member of the multiple myeloma faculty here at the Jerome Lipper Multiple Myeloma Center at [the] Dana-Farber [Cancer Institute] in Boston, Massachusetts. It’s my pleasure today to go over some Case-Based Peer Perspectives regarding the treatment of multiple myeloma, and hopefully this will provide some helpful information and insight to help guide clinical practice.

Without further ado, here’s the case. This patient is a 79-year-old woman who presented with intermittent nausea, decreased appetite, and tingling and numbness in her feet bilaterally. She has a past medical history of hypertension that is controlled with medications. On physical examination, she’s thin and appears tired, but with an otherwise unremarkable exam. She is noted to have grade 1 peripheral neuropathy, and her ECOG performance status is good at 0.

The patient’s bloodwork is significant for a hemoglobin of 9.6 g/dL, a calcium of 10.5 mg/dL, normal LDH [lactate dehydrogenase], creatinine of 1.1 mg/dL with an estimated GFR [glomerular filtration rate] of approximately 35, an albumin of 3.8 g/dL, beta-2 microglobulin 3.2 μ/mL, an M-protein of 2.9 g/dL, which is an IgG [immunoglobulin G] kappa, and serum free kappa light chains of 4.4 mg/dL. She is negative for her hepatitis serologies, and the skeletal survey and MRI both show an osteolytic lesion in L3 and L4 without other evidence of osteolytic disease. A bone marrow biopsy shows 45% involvement by kappa restricted plasma cells. Multiple myeloma FISH [fluorescence in situ hybridization] panel reveals evidence of hyperdiploidy but no evidence of high-risk cytogenetic abnormalities. She was ultimately given a diagnosis of multiple myeloma, newly diagnosed with Revised-ISS [International Staging System] at stage I.

For her treatment, she was started on lenalidomide, bortezomib, and dexamethasone [RVd] for 8 cycles, followed by lenalidomide maintenance for approximately 9 months, at which time she unfortunately developed evidence of disease progression and was then started on selinexor plus bortezomib and dexamethasone in the second-line setting.

My initial impressions of this case are that this patient is a relatively robust, or nonfrail, 79-year-old woman with some but relatively few comorbidities, with standard-risk multiple myeloma in an early stage by Revised-ISS score. Importantly, she presented without evidence of high-risk cytogenetics and presented in a fairly common way. The only thing I’ll say about her presentation that may be, not atypical, but is worthy of mention, is that many patients present with peripheral neuropathy. I find that a majority of this is related to the paraproteinemia, but it is not indicative of coexisting amyloidosis. At least a basic screen and review of systems to hopefully exclude evidence of coexisting amyloidosis is appropriate in this kind of presentation.

In terms of her treatment, it was pretty spot on. She was given the RVd [lenalidomide, bortezomib, dexamethasone] regimen. The dosing wasn’t specified; however, for patients in their late 70s to 80s and beyond, we generally give an RVd [lenalidomide, bortezomib, dexamethasone]-lite dosing schedule, which we [at the Dana-Farber Cancer Institute] have studied extensively here in Boston. We have found it to be well tolerated in patients in this age group with manageable peripheral neuropathy and relatively infrequent high-grade toxicities. This is in the form of once-weekly as opposed to twice-weekly Velcade [bortezomib] with an interrupted schedule and a decreased starting dose of both the Revlimid [lenalidomide] and the dexamethasone. In any case, she was treated very appropriately with approximately 8 cycles, and then with single-agent Revlimid [bortezomib] maintenance to follow, which would still be probably considered the standard of care.

However, I am increasingly considering patients for a dual-agent maintenance, what we call RV [lenalidomide, bortezomib] maintenance, when adverse effects or a lack thereof allow us to do that, given some fairly recent data from our colleagues in Italy who combined IMiD [immunomodulatory drug] and proteasome inhibitor maintenance and found that this may have advantages over single-agent IMiD maintenance alone.

She has a fairly good prognosis, relatively speaking, given her early stage disease and lack of high-risk cytogenetics. Even though she unfortunately did not have a durable first remission, developing progressive disease only 9 months into maintenance, hopefully with available options, she may still have a good chance of a good long-term outcome.

What I will say about the risk status is that, unfortunately, we sometimes find that, even in patients who we consider to be standard risk or early stage based on disease factors at the time of diagnosis, there are occasionally patients who prove themselves to have functionally high-risk disease, meaning that they unfortunately don’t enjoy as long of an initial remission as we expect. With these patients, I tend to treat them or view them with a lens of high-risk disease even in the absence of high cytogenetic risk at the time of diagnosis.

Transcript edited for clarity.

Case: A 79-Year-Old Woman with Multiple Myeloma

Initial Presentation

• A 79-year-old woman presented with intermittent nausea, decreased appetite and tingling and numbness in her feet bilaterally
• PMH: HTN, medically controlled
• PE: thin, tired appearing woman, otherwise unremarkable; grade I peripheral neuropathy
• ECOG PS 0

Clinical Workup

• Labs: Hb 9.6 g/dL, calcium 10.5 mg/dL, LDH 210 U/L, creatinine 1.1 mg/dL, albumin 3.8 g/dL, beta-2 microglobulin 3.2 mcg/mL, M-protein 2.9 g/dL, serum free kappa light chains 4.4 mg/dL, CLCr 35mL/min
• Hepatitis B and C negative
• Skeletal survey and MRI showed a lytic lesion in her spine L3/L4
• Bone marrow shows 45% clonal plasma cells IgG k
• FISH: hyperdiploid
• Diagnosis: R-ISS stage I MM

Treatment

• Initiated lenalidomide + bortezomib + dexamethasone for 8 cycles + lenalidomide maintenance for 9 months
• Follow-up at that time revealed disease progression
• Initiated selinexor + bortezomib + dexamethasone