A 78-Year-Old Man With Multiple Myeloma - Episode 1

Case Review of a 78-Year-Old Man With Multiple Myeloma

Sagar Lonial, MD, FACP, summarizes a case concerning a 78-year-old man with multiple myeloma, including initial impressions and prognosis at diagnosis.

Sagar Lonial, MD, FACP: I am Dr Sagar Lonial, professor and chair of the Department of Hematology and Medical Oncology at the Winship Cancer Institute at Emory University in Atlanta, Georgia.

This is the case of a 78-year-old gentleman who presented with a yearlong history of progressive fatigue. He is very active, but noticed that in the last few months he had been having joint and muscle pain. His past medical history included a myocardial infarction about 4 years ago, but he is well compensated, very functional. His LVEF [left ventricular ejection fraction] is about 45%. On physical examination he reported some tenderness on his hips and lower back associated with bone palpation.

His clinical workup showed a hemoglobin of 10.9 g/dL, a calcium of 10.0 mg/dL, an LDH [lactate dehydrogenase] of about 160 U/L. His creatinine was about 2.1 mg/dL, which is slightly elevated. His albumin was 3.3 g/dL, and his beta-2-microglobulin was 5.2 μg/mL. His M-protein was about 2.6 g/dL, and the lambda free light chain was about 4.1 mg/dL.

His initial hepatitis panel demonstrated that his hepatitis B profile was unremarkable. A skeletal survey and MRI revealed diffuse lytic bone lesions in the left hip, pelvis, and L2 vertebrae. Bone marrow showed about 70% plasma cells, which were IgG [immunoglobulin G] kappa restricted. FISH [fluorescence in situ hybridization] was unremarkable. At the summation of this information, he was diagnosed as having R-ISS stage II multiple myeloma with an ECOG performance status of 0.

As we begin to think about what was offered to him in terms of treatment, he was noted at that time to be ineligible for stem cell transplantation because of comorbidities. He was initially started on induction therapy with daratumumab, lenalidomide, and dexamethasone.

This is an interesting patient. When you talk about prognosis at diagnosis, this really has become a challenging situation. What we know about patients just given diagnoses of myeloma is that the median overall survival, particularly for standard-risk patients, is continuing to improve as we develop new therapeutic options.

In a recent retrospective study published by our group where patients were treated with RVd [lenalidomide, bortezomib, and dexamethasone] induction, single transplant, and lenalidomide or risk-adapted maintenance, we demonstrated that the median survival for all patients in aggregate is between 10 and 12 years. If you look purely at the standard-risk patients, the median overall survival has not been reached and is expected to be upwards of 14 years.

What this suggests is that we should not think about this as purely palliative, in terms of how we approach treatment. We should think about trying to use treatments that give the best and longest progression-free survival. One of the challenges in treating older patients with multiple myeloma is that they may not get to second-line therapy. We know that even in the younger patient population, roughly 15% to 20% of patients get frontline therapy but don’t get second-line therapy. And in the older, frailer population, that fraction continues to increase.

Although this patient did have a previous history of cardiovascular issues, particularly a myocardial infarction, at his age and functional status he would be somebody whom we would consider for a high-dose therapy and autologous stem cell transplant. Nevertheless, it’s certainly reasonable to offer him lenalidomide with daratumumab and dexamethasone, knowing that patients with standard-risk myeloma can have quite good outcomes. This would be a way to offer triplet-based therapy with very long follow-up in a randomized phase 3 trial.

Transcript edited for clarity.


Case: A 78-Year-Old Man with Multiple Myeloma

Initial Presentation

  • An active 78-year-old man presents with a year history of progressive fatigue; he feels joint and muscle pain diffusely for about 2 months
  • PMH: suffered a myocardial infarction 4 years ago; LVEF 45%
  • PE: bony tenderness appreciated on the hips and lower back


Clinical Workup

  • Labs: Hb 10.9 g/dL, calcium 10.0 mg/dL, LDH 160 U/L, creatinine 2.1 mg/dL, albumin 3.3 g/dL, beta-2 microgloblulin 5.2 mcg/mL, M-protein 2.6 g/dL, lambda free light chains 4.1 mg/dL
  • Hepatitis B negative
  • Skeletal survey and MRI revealed lytic bone lesions in the left hip, pelvis and L2 vertebrae
  • Bone marrow shows 70% plasma cells IgG k restricted
  • FISH: normal
  • Diagnosis: R-ISS stage II MM
  • ECOG 0

Treatment

  • Patient is ineligible for ASCT due to comorbidities
  • Initiated treatment with daratumumab + lenalidomide + dexamethasone