My question is about side effects with Venetoclax and Obinituzumab. I wonder if anyone out there has any insights.
I'm 66, was diagnosed in July 2020. Watch & wait until July 2022. Started Venetoclax and Obinituzumab in New York at Sloan Kettering. I’ve completed the Obinituzumab, and am now on the regular 400mg/day Venetoclax. A few bumps: Obinituzumab infusion reaction that first day, one urinary tract infection that needed to be treated, low hemoglobin that necessitated transfusions, one Covid bout. But overall, I’m now doing really well, hemoglobin back to normal, platelets higher. Feeling much better.
Except one thing. Early in December, my left knee started to flare up. Quite painful. I have a history with this knee, which has a known torn meniscus, so I went to an orthopedist who took xrays (nothing came up with fractures or arthritis) and who’s given me meloxicam to alleviate inflammation and recommended surgery. However, one blood measure is irregular: high Alkaline Phosphatase, which has been identified as coming from bone. As December progressed, my right knee has joined the party, even though I have no history of soreness or injury! The minute I put weight on either knee they get extremely sore, and I have to constantly ice it and either walk with a cane or avoid walking at all.
My CLL specialist/oncologist has recommended an Endocrinologist consult. My research indicates that the cause of the elevated Alkaline Phosphatase could be anything from thyroid conditions, to conditions such as Osteomalacia or Paget’s disease that weaken bones, to bone metastasis or Osteogenic sarcoma (both cancer in bones). I’ve had cat scans and pet scans in the course of my treatment with no indication of secondary cancers.
I’m anxiously awaiting my meeting with the Endocrinologist. In the meantime – any experience with this out there? I know joint pain is a side effect of some of the drugs, seems like it's more of an issue with BTK inhibitors.
Thanks for reading and thanks in advance.
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DinosaurDad
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How high are your ALT results? As you've discovered, there are many different potential causes. Doctors don't tend to get concerned with readings up to several times the upper reference limit. Mine gradually increased during my treatment course with acalabrutinib, venetoclax and obinutuzumab, peaking at 66 (upper limit is 55 for my pathology lab). That was 3 months after I finished treatment. It didn't begin a gradual climb until I had been on 400mg of venetoclax for 3 months and it only really started climbing steeply about 6 months after commencing venetoclax - almost about the time you are at now. It was pretty well in the normal range during the two months after my last obinutuzumab infusion. My ALT is now back at the top end of my normal range, nearly 2 years after having the last of my acalabrutinib and venetoclax doses. I had occasional fairly painful hip joint pain during treatment, particularly in the mornings. That too has totally gone.
I hope you can gain some comfort that bone cancer is unlikely, given (a) your previous history with your left knee and (b) that your right knee has joined the party. I hope you can get this resolved soon; walking is very important to our health and it's pretty debilitating to experience pain from basic daily activity.
Many thanks for your response AussieNeil. If by ALT you mean Alanine Aminotrasferase, it's been in the normal range throughout. On the other hand, my Alkaline Phosphatase, back when starting treatment in September 2022, was 144 (norm is <=130). It remained in that range through September, then increased to 157 by early October, then to the 170's since mid-October. My CLL specialist did a special test recently and discovered this elevated level is coming from bone (it can also come from the liver): my Bone Alkaline Phosphatase is 47.7 (normal 0-20.1).
Right now it's a bit of a mystery to me. My CLL specialist said that she needed to bring in an Endocrinologist to rule some things out given the high levels, and I'll probably need more testing with them. Meanwhile, my orthopedist was looking to treat the knee issue (focusing on the left knee) as purely a meniscus/mechanical thing, but now we have this new information. So is the high Bone Alkaine Phosphatase score a proximate cause of my knee pain? Or is something else causing it? This is one of those questions that may cross specialty consultant areas. So right now I'm anxious to get the right experts to weigh in and help get the right diagnosis. Unfortunately it's pretty painful despite the meloxicam, so I have to really restrict activities.
So strange this is happening while overall I'm doing great: my other key measures like platelets, hemoglobin, neutrofils are normal and lymph node swelling is gone.
Could not agree more about the importance of daily exercise...I haven't been able to do much of anything for about 6 weeks now. Hoping for a fast answer to the questions!
Sorry, wrong liver enzyme. Indeed, to quote from my early research "elevated ALP indicates that there could be active bone deposition occurring as ALP is a byproduct of osteoblast activity (such as the case in Paget's disease of bone)." and "ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver."
Dr Susan Leclair noted that when "it is not clear whether this is due to liver or bone disease, then tests for ALP isoenzyme tests may be done to determine the cause." which I presume you've had. Dr Koffman has also noted that the most common cause is still from the liver.
My ALP stepped up to a temporarily higher level from around 60 to 70 in watch and wait to around 80 during treatment. It's dropped back to around 70 since.
I am not sure these things are relevant, however, It may help simplify the troubleshooting through process of elimination. There never seems to be a shortage of what if's.
I think the enzyme that Smakwater was referring to was CYP3A4. I think drug interactions are usually first seen in high ALT (alanine aminotransferase).
I had a very high ALP, along with high ALT and AST when I had a gallbladder attack caused by turmeric, butter, and black pepper making my gallbladder squeeze some existing gallstones. Another symptom of gallbladder attack is pain in the upper back. I had a cholecystectomy.
So I think if it's just high ALP, and other liver enzymes are normal, that's something different from liver dysfunction. The endocrinologist will surely know best. I'm just an amateur, armchair medical generalist.
> high Alkaline Phosphatase, which has been identified as coming from bone.
How did they identify it coming from bone? I'm curious, because I'm about to start treatment, and I, too, have meniscus trouble in my knee.
Thanks for your response. The first test was Alkalline Phosphatase; my level is now 172 vs. a norm of <= 130. Then they did a Bone Alkaline Phosphatase test and I scored 47.7 vs. a norm of 0-20,1. The latter test identifies that it was coming from bone and not liver. Finally they did a Gamma Glutamyl Transferase Plasma test, which measures an enzyme mainly in the liver that can leak into the bloodstream indicating a liver issue) - my score was normal.
At first I thought my left knee issue traced to a diagnosis of torn meniscus two years ago via xrays and an MRI. I went to an orthopedist, and his recommendation was arthroscopic surgery, given that earlier I just did physical therapy and got a cortisone shot. But then my right knee acted up, and thus I had pain in both knees. Just seemed weird to have issues in both all of a sudden, with swelling and tenderness on the inside of both knees. Right now I just want to herd these various specialists, get the right diagnosis, and figure out how to proceed, as this pain is really debilitating, I'm basically just sitting around all day. Ugh.
Thanks for the additional info. I'm expecting some joint pain, because I already have joint pain from osteoarthritis. It's good to know there are tests that can narrow down the source.
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