At what low levels of A and G should I consider infusions? Went thru B&R 13 months ago and levels are not quite in the normal range(L), although "M" is slightly into the norm. I've heard about Hizentra but have not yet been totally on board with beginning. Any advice ?
Low Immunoglobulins A and G : At what low levels... - CLL Support
Low Immunoglobulins A and G
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Soflajoe
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AussieNeilAdministrator
The only Ig component with a level which influences an approval for supplementation is IgG. IgA is actually filtered out of the likes of Hizentra Gammagard, etc as it can cause anaphylactic shock in IgA-deficient patients with anti-IgA antibodies. I haven't heard of this happening in CLL patients and in fact, the company which makes Hizentra, was investigating producing an IgA infusion product a few years back.
To qualify for IgG supplementation by IV or subcutaneous delivery, you need to have both a sufficiently low level of IgG and some recent severe infections. The IgG threshold varies by country and is typically 400 or 500 mg/dl (4 or 5 g/l).
Neil
Just confirming Neil’s response. In New Zealand the trigger point for IGg is 500. They won’t be nearly as interested in A or M. Go well.
My reading 0.70 for igG , reason was manmade after taking FCR 2018 for CLL in remission ever since , have 2 lymph nodes in chest gone from 7 cm to 18 cm over 2 years
As always, AussieNeil is spot-on! My IgG has hovered around 420 for the last three years, but I've not experienced any serious health issues (I'm taking Zanubritinib... Brukinsa). Due to scarcity and other issues, my ONC/HEMO assures me most insurance companies would almost certainly refuse to cover the expense (again, lacking any other serious chronic problems). BTW, I understand that infusions include a number of potential side effects... something those of us being treated really don't want/need.
I have been on IVIG for several years and apart from feeling tired afterwards I have had no side effects ! Which ones were you referring to.
Colette
Hi Colette. IVIGs are pretty much the same for me. Just tired after the infusion.
I hope that you are doing well.
Chris
Hi Chris,
Can’t remember if I mentioned but Afib discovered just before Christmas so Ibrutinib has been paused for more tests. A bit disconcerting after nearly six fairly trouble free years, but I suppose it’s better I know.
How close is retirement now 🤞
Colette
I'm sorry to hear that Colette. I have minor heart problems now and have to take meds for that. I take so many pills these days that I split them up between morning and night.
I'm retiring in April so not too far off, but the days seem to go by slower when I know that that time is coming...
Chris
I also take loads now as well, but the main problem is checking that I don’t run out because some on two month repeat and some three and all started at different times.
Enjoy April. I can’t tell from your profile picture what sport that is ?
Colette
Yes, that is my main problem as well. In fact I have one that I need to call my CLL doc about today after work to get refilled.
That picture is from a fly fishing retreat for veterans suffering from cancer that I went to not to long after completing FCR almost six years ago. I still fly fish with my son once in a while and hope to do much more one I retire. My wife and I also have an RV that we hope to use often when retirement comes. Lots to look forward to.
Chris
Have been getting IVIG since 2016. No side effects whatsoever except for tiredness due to the Benadryl I get before the infusion.
I stopped the Benadryl ages ago, but still tired. I think it’s the boredom factor and unable to concentrate.
Colette
You could be right! I kinda’ like getting the benedryl because we have to drive 90 minutes to the cancer center and have to get up at 4:30 or so to get there by 9:00. The benedryl helps me to get a little nap, but I am not a daytime sleeper. By the time we are headed home, I am exhausted but not sleepy. It is amazing how it can tire you out. Would like to switch to subcutaneous but doc doesn’t want to have to go through the approval process again.
That’s a very early start.
I know Neil is a fan of subcut but I always look away when anyone comes near me with a needle, silly considering how long I have had CLL. I have a friend who tried but found it uncomfortable.
Colette
BeckyLUSA -
Try SCIG (SubCutaneous ImmunoGlobulin, aka SubQ or SubCu).
You do it at home weekly after a nurse comes out a few times to make sure it goes well. It's one fourth the dose, so less side effects. Weekly dosing maintains a higher average IgG level. The needles are smaller, and usually you inject in the belly, alternating sides. I only ever had local redness and swelling. They give you lidocaine and benedryl, but it's up to you whether to use them.
They ship it to your house every few months with cold packs. I usually specify to sign for the shipment, because I don't want anyone to steal it. I save the cold packs for re-use.
Studies have repeatedly shown fewer side effects and greater patient satisfaction. You can even travel with it.
=seymour=
Thought about it. But it is harder to get approved for IViG now with the shortages. My number is definitely below the minimum required, but I have not had a serious infection in over 4 years. He says he doesn’t want to rock the boat since we would have to go through the approval process all over again if we switched to subcutaneous. The way it is now, my blood test on the day of my infusion determines IF I get one the following 6 weeks. So far always well below the minimum. We tweaked the schedule by trial and error a few years back. 6 weeks is the sweet spot for me. Go over 6 weeks I am prone to catch something. At 1 month, my number is a little bit too high.
mrsjsmith Colette, in my trial of CLL patients who opted to transfer from IVIG to subQ, the only patient who transferred back was someone who was I think approaching their 90s and living alone. She wanted to stay on subQ, but the haematology clinic wanted to keep a closer eye on her. I didn't like the idea of using needles either, but found the fine subQ needles far more preferable to the IV cannula insertions.
Seymour, with respect to travelling with subQ IgG, the only proviso is that it needs to be kept between 0 and 25C, so you need to keep it with you in the cabin, ideally surrounded with melting ice packs (0 degrees C maintained) and, with the prior approval of the carrier, arrangements to keep it refrigerated if the aircraft has fridge capacity. Not all aircraft holds are temperature controlled and if left on the tarmac, it can quickly warm. It's super easy travelling with IgG compared to travelling with G-CSF injections, which need to be kept between 0 and 4C.
In my first overseas trip with IgG, I made the mistake of not keeping my IgG with me. I nearly lost it twice! I packed a weather station on top of the bag carrying my IgG and I've attached the resulting plot of temperature and air pressure. The first third of the plot is the day's travel by bus to the international departure airport. You can see a drop in air pressure when the bus gradually climbed over a mountain range before a rapid descent. The mid part of the plot is the flight to Dubai; you can see the drops in air pressure as the aircraft burns fuel and climbs to higher cruising altitudes. The drop back to atmospheric pressure and the rise in temperature was during the transfer time in Dubai - just a couple of hours. It was about 38C/100F at 5:30AM on arrival and you can see how the outside temperature quickly rose, then began to fall again on the flight to Europe.
Neil
Keep IgG with you (packed in melting inice) or refrigerated at all times when travelling.
Thank you Neil, I won’t tell my friend who is in his mid 50’s and lives with his wife. He was also surprised by the sudden appearance of a fridge from the hospital. I do understand it will suit many patients, but personally I am in the squeamish group. I even look away on the TV although I know it’s all fake. Lots of gore in the latest episode of Call the Midwife !
Colette
I look at my ivig infusion as a little vacation. My Center gives out warm blankets, snacks and benadryl to help you nap!
Soflajoe -
In the U.S., Ig Replacement Therapy (IgRT) is not usually triggered solely by the IgG level. IgRT can be IVIG (IntraVenous ImmunoGlobulin), or better yet, SCIG (SubCutaneous ImmunoGlobulin, aka SubQ or SubCu).
The problem is the insurance coverage, because it's really expensive. Immunoglobulin replacement costs US $15,000-$20,000 per month. In the U.S. you'll probably need co-pay assistance, but Out-of-Pocket-Max limits your damage. Insurance companies and Medicare each have their own guidelines. The doctor also has to code the claim properly, which doesn't happen automatically, because it's complicated. Experienced hemo/onco's know how to do it. In a pinch, you can see an Immunologist, who may know to code it differently.
The Medicare document that appears to apply is:
cms.gov/medicare-coverage-d...
"Other Disorders:
a. Chronic Lymphocytic Leukemia with associated hypogammaglobulinemia. To initiate IVIg for this disease, the IgG level should be less than 600 mg/dl or there should be evidence of specific antibody deficiency and the presence of repeated bacterial infections."
The Specific Antibody Deficieny clause refers to poor vaccine response to a polysaccharide vaccine (usually pneumovax23, I believe). That requires that you get a vaccine titer test - test, then vaccine, wait 6-8 weeks, test again, and compare results:
uptodate.com/contents/speci...
The ambiguous punctuation in the Medicare document may allow approval or denial with or without infection. But usually, I think the presence of repeated bacterial infections (not viral!?!) is expected, because of this document:
cms.gov/medicare-coverage-d...
"Prevention of recurrent bacterial infections in patients with hypogammaglobulinemia associated with B-cell chronic lymphocytic leukemia (CLL)."
There might be another Medicare document that clarifies the infection issue.
Insurance companies usually have a lower limit.
I've seen 500mg/dL and 400mg/dL cited, and they may require a specific number of infections, and may not limit to bacterial, or may not require any.
So there's not a consensus on this yet, even though many journal articles are written about the value of Ig replacement therapy every year. Those journal articles cite older articles that have differing Ig levels. It's not like if your IgG is 401, you get no infections, and at 399, you get a fever. The numbers are entirely arbitrary. They had to pick a number to do the studies and compare people. Also, your own sanitary habits have a large effect on the number of infections. Immunoglobulin replacement is also not going to allow you to mingle in a crowded bar without getting an infection. CLL and treatment affect more of the immune system than just antibody levels.
The issue around bacterial vs viral infections appears to me due to old dogma about antibodies and viral infections. It was once believed among medical students that antibodies fought bacteria, and T-cells fought viruses. But that was never completely true. It was based on old experiments and assumptions that even made it into textbooks and journal articles. We've seen a complete turnaround with the pandemic, where some people focus too much on antibodies and not enough on T-cells. But that's because of the Streetlight Effect
en.wikipedia.org/wiki/Stree...
Antibodies are easier to measure than T-cell responses.
Another issue is, "How serious of an infection?" I've seen different degrees, from long infections requiring multiple series of antibiotics to infections requiring hospitalization.
Why so much legal debate?It's based on donations of blood and blood plasma. You may see places called Plasma Centers in the U.S. that offer a fee for donations. This is ethically controversial. In other countries, it's based on voluntary donations.
In any case, urge your friends and families to donate blood and/or plasma. I wish I could donate, but none of us with CLL can.
=seymour=
Thanks Seymour for your response. Very insightful. My Immunoglobulin levels are my Achilles heel after receiving FCR back in 2015. All my other numbers are great and I have done very well Healthwise...except my immune system is crap. IGG=387 (was 510 when I started therapy in 2015. IGA=71 (was 41 in 2015) and IGM=<10! (was 13 in 2015). My WBC has now crept back up to 12.3 after staying below 10.0 until 2022. The absolute lymph is now 5.8 and Lymph % at 46.8. So the CLL is probably back. My CLL specialist says that if I am not getting bacterial infections, then you don't need an IGG supplementation. But viral infections? Oh yeah and they are rough. I get a simple cold and it goes right to my chest and I'm a respiratory mess for 4-6 weeks. Planes and crowded places are unavoidable unless I want to live in a practical bubble the rest of my life. I have had all the vaccines we are supposed to get, and it seems food and supplements are not helping (say no to colostrum.). I do get lots of sleep, eat a good balanced diet with fruits, veggies, fiber and no processed stuff (thank goodness my wife is vegan although I am more pescatarian and she tries to ensure I eat right...well most of the time. I'm from Chicago and we love our Pizza here.). Anyway, this is the one area I focus on a lot and where things develop in the future.
CClaver27 -
Your doctor is right, somewhat. The sure sign of a need for Ig supplements is infections. The bacterial part is dogma, in my opinion. Sad. You can also try going to an immunologist, and bring all your evidence of infections and your Ig test results.
In the U.S., the NCCN (National Comprehensive Cancer Network) Guidelines drive a lot of policy, including insurance. Insurance companies will sometimes cite it to justifty approval or denial. The latest copy is Cersion 2024.1, and it's usually updated several times a year. It says on Page CSLL-C, 4 OF 5:
" SUPPORTIVE CARE FOR PATIENTS WITH CLL/SLL
Recurrent Sinopulmonary Infections (requiring IV antibiotics or hospitalization)
• Antimicrobials as appropriate
• Evaluate serum IgG, if <500 mg/dL
Begin monthly IVIG 0.3–0.5 g/kg or may substitute a subcutaneous immunoglobulin (SCIG) product given weekly at appropriately adjusted equivalent doses
Adjust dose/interval to maintain nadir level of approximately 500 mg/dL"
Later, on Page MS-25:
"Supportive Care
Infections
Infectious complications are influenced by the progressive reduction in immunoglobulin levels (hypogammaglobulinemia) and are more common in patients with previously treated CLL. [261,262] Patients with heavily pretreated fludarabine-refractory CLL have high susceptibility to developing serious infections. [263] IVIG is associated with a significant decrease in the occurrence of infections but with no improvement in OS outcome. [264-268] Monitoring IVIG levels and monthly administration of IVIG (0.3–0.5 g/kg to maintain nadir levels of approximately 500 mg/dL) is recommended for selected patients with serum IVIG <500 mg/dL and recurrent sinopulmonary infections requiring intravenous antibiotics or hospitalization."
=seymour=
Reference:
nccn.org/professionals/phys...
NCCN Clinical P ractice Guidelines in Oncology (NCCN Guidelines ®) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCCN Evidence Blocks TM Version 1.2024 — December 11, 2023
You can download the above by creating a free patient account. There's also a separate, less detailed, Patient Guidelines:
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