Biochemical Progression of Stage II High-Risk Multiple Myeloma - Episode 1

Diagnosis of Stage 2 Multiple Myeloma

Ajai Chari, MD:We have a 61-year-old female who was diagnosed with symptomatic multiple myeloma. As a result, she was started on initial induction chemotherapy. Her staging was stage 2, so she got lenalidomide, bortezomib, and dexamethasone (RVD triplet therapy), followed by transplant (as consolidation therapy) and lenalidomide (as maintenance therapy). Of note, she did have translocation t(14;16 at diagnosis), and, therefore, the decision was to actually proceed with the maintenance therapy. Her remission lasted quite a long time—for approximately 5 years.

This 61-year-old female is relatively typical for multiple myeloma. The median age of diagnosis is approximately for patients in their mid-60s. However, it’s a very heterogeneous disease. Our youngest patient was age 18, and our oldest is over age 100. That heterogeneity also adds to the complexity of treating this cancer, because patients will come with various levels of comorbidities. Particularly, in the older patients, we now know that there’s increasing cardiac comorbidities that can affect their tolerance of different therapy and eligibility for transplant. So, it’s important to think about the patient’s myeloma in the context of their age and other medical conditions.

Multiple myeloma, as we know, unlike solid tumors, can’t be staged as localized or diffuse because it’s a bone marrow disease. The initial staging system used in the 1970s was the Durie-Salmon Staging System. While that was an important advancement, one of the criticisms of that was in regard to the lytic lesions that are detected by radiologists on skeletal imaging. The problem with that is a radiologist may say there are 4 lesions, while another may read it as 6. Therefore, you have some upstaging. It didn’t really seem to be reproducible, as much, and we didn’t get as good of a separation. So, along came, in 2005, the International Staging System, which was an effort to try to have a more simple staging system. This is based on beta 2-microglobulin and albumin, and it’s globally reproduced and very simple. This allowed separation into stages 1, 2, and 3 with associated median survivals of 4, 5, and 3 years, respectively.

While this was a big advancement, we now know that in all of oncology, molecular information is very important and it helps risk stratify patients even further. So, the latest version of myeloma staging came out in theJournal of Clinical Oncology, in 2015, by Dr Palumbo, et al., This staging system includes the International Staging System (based on beta 2-microglobulin and albumin), but it now also incorporates LDH (lactate dehydrogenase) and molecular risk.

In particular, high LDH is considered high risk, and certain findings by the FISH (fluorescence in situ hybridization) test, including translocation t(4;14), translocation t(14;16), and also deletion 17p, are typically considered high risk. So, now we integrate all of that. The reason this is an advancement is now we can segregate patients into median overall survival for stage 1 (of not even reached), stage 2 (of approximately 7 years), and stage 3 (of only 3.5 years). Clearly, this illustrates that it’s this high-risk population that still has an unmet medical need, despite all of our new drug approvals in myeloma.

Transcript edited for clarity.

Biochemical Progression of Stage II Myeloma

July 2011

  • A 61-year-old Caucasian female was diagnosed with stage II multiple myeloma
  • Genetic testing showed t(14:16)
  • At the time she was treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy followed by autologous stem cell transplantation
  • She achieved a near complete remission with RVD and transplant
  • Based on her high-risk cytogenetics, the patient was placed on lenalidomide maintenance therapy

August 2016

  • On routine follow up, the patient reports having mild fatigue but continues to work full-time; she has grade 1 neuropathy
    • M-protein, 1.3 g/dL
    • SFLC, kappa, 150 mg/L
    • Hb, 10.3 g/dL
    • Creatinine, 1.3 mg/dL