Testing and Therapy Options for Relapsed Stage II Multiple Myeloma

Cristina Gasparetto, MD:This case is a 61-year-old man diagnosed with multiple myeloma. At the beginning of 2015, it became stage II multiple myeloma. The patient received induction therapy with RVD, which is a combination of lenalidomide, bortezomib, and dexamethasone. After the initial induction therapy, he achieved a partial response and then he proceeded to consolidation with high-dose chemotherapy and autologous stem cell transplant. After transplant, he achieved a complete remission. He was actually MRD-negative. But unfortunately, the duration of his response was not so durable and was not so long. He progressed clinically in May or April of 2016, so not even 1 year after transplant. The patient was started on induction therapy with lenalidomide/dexamethasone/bortezomib, which is still considered the standard of care in preparation for transplant. Maybe this will change in the near future with a junction of other drugs, like daratumumab/elotuzumab. We are testing other chromosome inhibitors in an induction, but for now, lenalidomide/bortezomib/dexamethasone remains the standard of care in this situation.

Transplant is still a very important piece of the treatment algorithm for the majority of patients with myeloma. A transplant was introduced more than 20 years ago and questioned the treatment algorithm recently, but we have 4 large randomized studies published, presented in large meetings, showing that transplant earlier remains an important part of the treatment algorithm. High-dose chemotherapy followed by transplant allows patients to achieve a deeper response and deeper remission and that translated to a longer durability of their responses. So, transplant is still very important.

MRD testing is becoming very important. It’s clear from many recent studies that the achievement of MRD negativity translates to a longer durability of response, a longer overall survival. MRD is becoming an endpoint of many treatments, particularly for newly diagnosed patients like in the case that we presented. So, yes, after transplant, I would probably test this patient for MRD negativity.

Right now, at Duke, we’re using a flow cytometry for MRD. We don’t have studies comparing the 2 methodologies, the sequencing with the flow-based analysis. They both have pros and cons. Sequencing is probably a more sensitive test, but, again, we have not compared it with flow analysis. You need to have this placement of the bone marrow sample at time of diagnosis for comparison. The flow analysis, you don’t need that. You can do it in any patients, in any situations. So, it’s easier. But the flow analysis is also very cumbersome, and you need to collect many events to achieve the same sensitivity of the sequencing.

I don’t use PET/CT routinely. However, in the future, we’re going to see that because with the MRD, we only test spots when we do a bone marrow biopsy. By definition, myeloma is some patches. So, patch areas are always in multiple places. The combination of MRD and PET/CT would probably give us a bigger picture. But right now, it’s difficult to combine 2 tests for patients. So, occasionally, I do the PET/CT and I try to do MRD in all the patients after transplant.

Case Scenario 1:

January 2015

• The patient is a 61-year-old male who was diagnosed with ISS stage II MM.
• Performance status 0.
• He was treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction.
• He achieved a partial response with RVD.
• He then had an autologous stem cell transplantation and achieved MRD negativity.
• He was started on lenalidomide maintenance of 15 mg.

April 2016

• Patient was experiencing back pain, loss of appetite and weight loss.
• Upon relapse cytogenetics showed a 17p deletion detected by FISH, demonstrating progression of his disease.
• Beta-2 microglobulin=4.0 mg/dL, Hg=9 g/dL, creatinine=1.2 mg/dL, multiple bone lesions, bone marrow biopsy=70% plasma cells.
• Performance status 1.
• Based on these criteria he was diagnosed with standard-risk multiple myeloma.
• He was started on daratumumab, bortezomib, and dexamethasone.