BY PAUL KLEUTGHEN In January 2014 I was diagnosed with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma. My treatment at the Duke Adult Bone Marrow Transplant center included a tandem auto stem cell transpant after which I achieved stringent complete response (sCR). I must say, however, that I attribute that success mainly to the efforts of my wife of 39 years, Vicki, who has been my advocate and caregiver since diagnosis and who is affectionately labeled as “The Warden” by our family and friends. Since about 16 months after my second transplant I have had multiple excursions of my kappa/lambda ratio outside the normal range but have had no other evidence of active disease. Technically, these excursions put an end to me having a sCR. My cancer was originally characterized as IgD lambda but we have been seeing the presence of IgG kappa in serum free light chains. We (patients and caregivers) have all become so attuned to focusing on numbers that any excursion out of the “normal” causes worries and sleepless nights. My physician at Duke has been telling us that this is quite normal and is actually a “good thing” in that the “abnormal” reconstitution of my immune system, as evidenced by the presence of the noninvolved free light chain, has improved my prognosis (time to progression and overall survival). A few days ago he provided us with copy of a research paper recently published in the British Journal of Haematology (“Potential pitfalls in serum free light chain analysis to assess treatment response in multiple myeloma”, BJH May 2016) authored by Dr. Tricot’s team at the University of Iowa that may be of interest to some myeloma patients. This article is a retrospective study of 142 multiple myeloma patients with 12% having an abnormal serum Free Light Chain ratio but with otherwise no evidence of disease. In all of these “abnormal” patients the abnormal kappa/lambda ratio was caused by abnormalities in the kappa light chains. To quote the authors:

“Our results show that patients with MM can be in a deep complete remission with MRD negativity, but have abnormal κ / ʎ ratios if: 1) the ratio is abnormal because the noninvolved FLC is elevated while the involved FLC is normal; 2) the ratio is abnormal because the involved FLC is elevated, but there is no evidence of disease by MFC, FISH analysis on highly selected plasma cells of the bone marrow, or imaging (positron emission tomography-computerized tomography scan and magnetic resonance imaging fails to show new or active lesions). In none of our patients was the planned treatment altered based on the isolated abnormal FLC. None of the patients with abnormal sFLC ratios had shown evidence of myeloma progression at the time of last follow-up. “ (Emphasis added).

In other words, patients need not worry if the ratio is thrown off because the "other" light chain went up or down (for example, if the lambda ratio changed when you have kappa myeloma) or if the ratio is changed and there is no other evidence of disease in other blood, bone marrow or imaging testing. The prognostic value of normal serum Free Light Chains has also been questioned elsewhere. The authors suggest that the International Myeloma Working Group (IMWG) criteria for stringent complete response be adjusted to reflect that some patients can have sCR even when their light chain ratios fall outside the “normal” range. One more worry can go off the list for those patients where this “abnormality” is seen.

"Normal" Ranges (according to the University of Utah - other facility standard ranges may use different values or ranges)

• Kappa Qnt Free Light Chains: 3.30 - 19.40 mg/L
• Lambda Qnt Free Light Chains: 5.71 - 26.30 mg/L
• Kappa/Lambda Free Light Chain Ratio: .26 - 1.65