Can flow cytometry predict multiple myeloma outcomes?

This study looked at how flow cytometry (FC) measurements predicted outcomes for patients with multiple myeloma (MM). It found that patients who had no traces of minimal residual disease (MRD) by FC had better outcomes.

Multiple myeloma (MM) is a blood cancer involving abnormal versions of plasma cells. Like plasma cells, myeloma cells create small proteins of the immune system known as antibodies. However, myeloma cells create very large numbers of antibodies, which can then clog up organs such as the kidneys. Myeloma cells grow within the bone marrow and circulate in the bloodstream. Myeloma can form plasmacytomas, tumors of plasma cells that often develop in the bone. Although MM cannot be cured, treatment can lengthen and improve the quality of life.

How well a patient responds to treatment is an indication of how long before the cancer progresses (worsens). A complete response means that there are normal antibody levels in the blood, and there are no plasmacytomas. However, it does not indicate whether there are myeloma cells circulating in the blood.

Flow cytometry (FC) examines individual blood cells using a machine which can separate the cells and detect how light interacts with their surfaces. If there is a complete response but myeloma cells are detectable by flow cytometry, there is minimal residual disease (MRD). It is not clear whether testing for MRD by FC can predict MM outcomes.

This sub-study used data from a larger study of 1197 patients receiving initial treatment for MM. Patients were treated with either stem cell transplant or the VMP (bortezomib, melphalan, prednisone) regimen. 449 of the patients also received consolidation, or a second round of treatment, with VRD (bortezomib, lenalidomide, dexamethasone). All patients who had a complete response were offered the option to test for MRD with FC. The sub-study included 947 patients who agreed to FC testing or who did not have a complete response. Patients were followed for an average of 75 months.

Significantly more patients without MRD (66%) were alive without MM progression at 5 years compared to those with MRD (31%). Also, significantly more patients without MRD lived at least 5 years (86% vs. 69%). The patient’s MRD status predicted outcomes better than the cancer’s stage or genetic mutations (FISH panel).

Autologous stem cell transplant (ASCT; stem cells transplanted from the patients themselves) led to better outcomes than the targeted treatment VMP. Not having MRD was connected to better outcomes for patients with both types of treatment. Patients who were treated with ASCT and had measurable MRD had 44 months before the cancer progressed on average. In contrast, the majority of patients treated with ASCT without measurable MRD did not progress before this study was published.

118 patients received maintenance treatment (treatment given after a first line of therapy to keep the cancer from coming back) with lenalidomide (Revlimid). Significantly more patients who received lenalidomide maintenance and were MRD-negative were alive at 5 years without MM worsening compared to those with measurable MRD (79% vs 48%). Also, after 1 year of maintenance treatment, 42% of the MRD-positive patients became MRD-negative.

This study found that measuring MRD with flow cytometry can predict outcomes for patients with MM better than other methods such as the cancer stage. It also found that stem cell transplant and lenalidomide maintenance leads to better outcomes.

The techniques for MRD testing are continuing to improve. The method used in this study, multiparameter flow cytometry, is not as sensitive as other methods currently available. Also, doctors are still determining how to adjust treatment based on MRD results.

If you have had a complete response to MM treatment, discuss with your doctor whether MRD testing is right for you.