Lymphoplasmacytic Lymphoma that is not WM?

Hi yes my wife has LPL IgG with Kappa Free Light Chains and MYD88 WT with systemic Neuropathy. She was diagnosed around 2 years ago because of the Neuropathy and it has been an absolute nightmare getting the Neuropthy linked to the LPL. She has seen the best in the UK and they said the symmetrical foot numbness was caused by a slight S1 left sided Radiculopathy. She finally has a new neurologist say that she may have sensory Neuropathy but not SFN as she has length dependant Neuropathy and this fits but the numb lips etc. don't fit as you can't have both length and non length dependant SFN, I have tried so hard to convince them this may not be actually true? and I think she actually has mixed fibre Neuropathy as there is reduced vibration senstivity in both large toes. So we thought we had got somewhere and now he says it is caused by Hypervigilance so we assume Function Neurological Disorder (FND) is what he is saying, but the symptoms just don't fit. So treatment is refused. I was hoping that she would start on Rituximab very soon then if the efficacy was not good enough to explore more intense treatment such as BR. The Neurologist said they don't want to start treatment in case they are wrong. This is a horrible illness and LPL IgG or other non IgM LPL are very poorly understood and basically ignored in the UK. I would be interest to know how others with non IgM LPL and Neuropathy presented? and how was it treated or found? she also has excess thirst nearly a gallon a day, weird transient ECG inverted T waves, and bowel issues all told not linked and skin lesions that come and go that maybe linked to her LPL but still not biopsied. Thanks Jon

@jerry48 did the treatment help the neuropathy, my wife has LPL IgG with kappa free light chains and MYD88 WT but they are refusing treatment. Her Neuropathy started in her feet symmetrical, now in both hands and lips are numb yet they still refuse treatment.

I am only 2 weeks into an expected 4 to 6 month course of treatment with Rituximab- Bendamustine. No change in my peripheral neuropathy as of now. Hopefully it will not get any worse and we hope for some improvement. The PN is the only symptom I have. Full neuro work up could find no other cause so we are assuming the high light chains are causing the axonal dysfunction seen on NCS and EMG. The goal is to get light chains down from 400 to a normal level. (About 20 I think)

@jonyb
I can only imagine the frustration. My heart hurts for your wife, and you. It’s also difficult in the U.S. to find any studies and/or clinical trials for non IgM LPL.
I started with Rituximab by itself- the least toxic first line of treatment. I have not had any neuropathy pre/post treatment.
I wonder if high Kappa vs high Lambda light chain makes a difference in neuropathy? Or the MYD88 Wild mutation vs non Wild.
So many questions which are hopefully being addressed in the labs.
Keep advocating for your wife. Sending strength!

@jerry48 Hi Jerry thanks for your reply. It is a relief to finally find others with similar symptoms and condition, however I am sorry you all have this condition. Anna has a very steady IgG level in UK figures 16 to 19 g/l, however her kappa free light chains have been steadily rising from around 50mg/l now to around 90mg/l, kappa lambda ratio now over 25 if I remember. Her symptoms suddenly got a lot when the FLC rose above 65. We have suggested that hers is probably light chain driven as this seems to be the active element but we struggle to get them to even check them. NCS/EMG is normal for Anna. We both really hope treatment works for you, let us all know how it goes. Thanks again for your reply.

@monicalu2626 Thanks for your reply Monica, yes having Wild Type rather than the L265P mutation is not a good sign generally but Anna has a very bright CD20, so CD20++ so Rituximab should work well. So what were your symptoms to start treatment if not neuropathy?

The problem is that Haematology in the UK will not investigate Anna's symptoms and Neurology has been very bad. The UK expert even warned us about going to the States for a diagnosis as she inferred that they may just tell us treatment is required just to get our money for treatment. We can't afford treatment in the USA anyway but were considering coming for diagnosis only. However Dana Faber never replied when I tried to get a quote. LPL IgG is so ignored the World over. Thanks again so much for replying we don't feel so alone now. Jon

@jonyb
I’m glad to meet everyone who has joined this group, as it’s so hard to navigate this disease. None of us needs to feel alone!
My initial symptom was lower than usual hemoglobin in 2022 however, during the pandemic I had donated blood and platelets as often as I could, because they were needed. My primary doc and I thought that my body just needed to recover.
2023 I was experiencing unusual fatigue but my bloodwork wasn’t too bad. Mid 2024 the fatigue was nearly debilitating and we watched my hemoglobin drop from 11 to 8.5 over a three week time period.
Was sent to hematology. An iron transfusion made no difference. Then I got a body xray (initially thought I had Multiple Myeloma), CT, Pet, etc
November 2024 diagnosed with Splenic Marginal Zone Lymphoma.
Since then, after going to Mayo recently, the diagnosis is changed to IgG LPL.
My docs tell me that treatment is indicated if my hemoglobin starts dropping, given that my bone marrow is the main cancer location.
I have fired two docs and think I have a good team in place now. Fingers crossed.
Hang in there!

@monicalu2626 We sold our lovely house in the Highlands of Scotland and moved near Edinburgh just to get to a better Hospital. I am not sure if anyone is good in the UK? there is a good Neurologist in Glasgow who has helped a lot, but that is about it.

Hi everyone, this new interactive webinar was just announced.
Navigating a Rare Lymphoma

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Hello all, especially @jonyb, hope your wife is hanging in there. I got diagnosed about 10 years ago with both IgM (WM) and IgG kappa LPL. (and elevated kappa FLC) No symptoms to speak of and never needed treatment for them. Two years ago a third mutation, also IgG kappa, and more kappa FLC, showed up diagnosed in the end as CLL. Still no symptoms but started zanu treatment 4 months ago due to ever increasing new IgG/FLC and it's working well. I've been tracking the original LPLs at the IWMF forum https://groups.io/g/iwmfconnect/and suggest that you do likewise as the best source of relevant Ig LPL. So, here is what I have gleaned and my opinions. The rarity of non-IgM is a problem since only 75 cases per year are diagnosed in the USA compared to 1500 per year of WM.

First, solo Rituximab is not commonly prescribed to treat these conditions. Treatment options deserve their own posting, except to say that since both Ig types are similar B cell lymphomas, WM treatments are the first choice. And only treat due to symptoms that might include anemia. What symptoms led to your treatment?Bone marrow per cent is not the best way to keep track. Percentages don't track well with blood tests or symptoms.

The best way to track the LPL is testing total IgG and FLC, but supplement IgG number with SPEP and immunofixation which will give an M spike number representing the level of monoclonal IgG which is the culprit. For years my total IgG fluctuated between 1400 and 1900, upper normal range around 1500. But M spike ran around 1100-1300 indicating that most of it was monoclonal IgG kappa consistent with FLC kappa. IgM numbers ran 600-1200. BTW, in general kappa anything seems to be better than lambda.

Every WM expert I consulted formally or at educational forums were candid about the rarity problems of IgG LPL and scarcity of data but in the end all had success treating it like WM with anemia due to cancer cells in the marrow out competing normal cells for space. None had significant experience with elevated IgG causing significant problems. Jonyb's wife has unique, complicated issues compared to my uneventful journey. Never got into researching FLC much since they were only slightly elevated during my LPL days but really took off when the CLL IgG kappa clone showed up.

Enough for now.