ASH 2017: Quick ‘Do-It-Yourself’ M-Spike Calculation, the Gamma Gap

There are two similarities between ALL multiple myeloma patients : we are all gluttons for test results, and live by the ‘numbers’, AND we detest having to wait for test results to come in. Some of our treatment centers have responded to the need for patients wanting to discuss test results when they visit with their physician and they make ‘mail in test-kits’ available. Blood can be drawn at our local treatment center and they, in turn, forward the plasma to the labs of our myeloma specialist. Many of us, however, will need to wait for test results to be posted once the myeloma blood panel has been analyzed, reviewed by our specialist and then passed on to us, the patients. We all deal with lab results that will take several days, and in some cases, up to a week, to be released to us. One of those results is M-spike. We know that myeloma results from malignant neoplasms, cells that look different from ‘normal’ plasma cells, and myeloma is often characterized by the production of large amounts of nonfunctional, monoclonal immunoglobulins (M-spike). M-spike is a surrogate marker for both disease burden and treatment response. The M-spike numbers that we wait so anxiously for is computed from the lab results of Serum Protein Electrophoresis (SPEP) or Urine Protein Electrophoresis (UPEP). The lab turnaround time for SPEP averages around 3 days and it typically takes about 7 days for UPEP results to become available. Compare that to, for example, the turnaround time for a comprehensive metabolic profile (CMP) : typically less than one hour. These delays can make the visits with our specialists less than productive and while we wait we just fret and resort to chocolate (high satisfaction and low co-pay). There is an interesting paper that will be presented at the upcoming ASH conference, titled “The Gamma Gap: A Point-of-Care Test That Correlates with Disease Burden and Treatment Response in Multiple Myeloma” authored by Dupuis, et al., from Duke University. The research team sorted through nearly 700 patient records and identified a total of 200 MM patients with …

“ … detectable M-Spike either undergoing treatment (including relapsed bone marrow transplant patients) or surveillance only, and had both an SPEP and a complete metabolic panel (CMP, including albumin and total protein drawn within 2 weeks of each other). We assessed patient data at three timepoints: at the beginning of treatment, midway (halfway through the total number of cycles received for a given treatment strategy), and at the end of a given line of treatment. Treatment responses were defined using standard IMWG response criteria.”

The authors next calculated the Gamma Gap (GG) :

“The calculated difference between a patient’s total serum protein and albumin. In patients with a substantial serum M-spike, the GG is typically elevated since excess myeloma-derived immunoglobulins elevate total protein but not albumin.” Statistical analysis showed that there is a very high correlation between M-Spike and the Gamma Gap and they devised three formulas (one for beginning, one for the midpoint and one for end of treatment) where one can calculate an estimate of M-Spike with results of two data-points that are readily available every time we provide a blood sample for a CMP. The authors also indicate that “GG is also a significant predictor of treatment response” [at all three different timepoints].

And there we have it : we can now estimate our own M-Spike before the actual results come in (or our physicians can do it) and now we end up with a more productive discussion with our MM specialist. In addition, in between visits with our MM specialist, when we go to our local treatment center for this or that infusion or injection, we can now compute our own Gamma Gap and estimate our own M-Spike. If we see the number go up in between visits with our MM specialist we can send a message to the specialist and let him/her know what is going on and not waste precious time for revised treatment decisions. It becomes part of advocating for ourselves and monitoring our disease progression on a more frequent basis with readily available information. And for those readers who are interested in the specific formulas, here we go :

• First calculate your Gamma Gap (GG) : the number for Total Serum Protein less the number for Albumin.
• Early in the treatment program : M-Spike = =-2.50+0.95GG
• Midpoint of therapy : M-spike=-2.33+0.88GG
• Towards the end of therapy : M-spike=-2.38+0.90GG

I would like to suggest that, if you have data points in your own medical records where you have M-Spike results from SPEP and/or UPEP AND CMP results from the same timeframe, you give these formulas a go. Remember that these formulas come from a statistical analysis, so you will not get an exact match with the ‘true’ M-Spike number that your lab has provided. Hopefully, though, the estimated number and the ‘true’ number will be close and then you will have a quick way to estimate your own M-Spike in the future. There will be patients, however, where the estimated number will differ a bit too much for comfort from the ‘true’ number. That is the nature of statistical models – they don’t work for everyone, but in this case the formulas should come close for + 80 % of patients. If your actual number is not close to the calculated estimate, I will suggest that you not use the formulas but, unfortunately, wait for the actual M-Spike number to be reported to you.