My father was diagnosed with aggressive CLL with PLL (prolymphocytic leukemia--where the cancer is present in immature white cells) and paraimmunoblastic features in March 2020.
The first-line treatment was obinutuzumab/venetoclax but after a year on this treatment, his disease has turned to a Richter's Transformation (large cell lymphoma). The transformed disease is concentrated in his right femur (6 cm of cancer), but the concern is that it is spreading rapidly because he is now feeling bone pain on his right side, and he is experiencing chills.
My dad has two options for his second treatment path:
Loxo clinical trial (1 pill a day)
Obinutuzamab-EPOCH chemotherapy with venetoclax
Which path would you advise taking and why? What experience do you have with these treatments?
He does not have 17P deletion, no TP53 mutation, but his IGHV is unmutated.
Thank you so much everyone for your wisdom, and I pray for everyone in this group every day.
Christine
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Phs2385
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Phs2385, I am not able to give remarks on your dad’s diagnosis. I simply don’t know enough. But I can send to you two, my biggest best wishes for a smooth navigation through this journey. There are many in this forum who will respond, who are more informed than me.
This is clearly a very complex medical issue for which you need to rely on a true specialist. However, you might also want to think through the logistics. Where would treatment be for each. How often. How far. How old is your dad.
I would be asking the docs do they know of others who progressed on obinutuzumab/venetoclax that responded on Obinutuzamab-EPOCH chemotherapy with venetoclax. In other words was the EPOCH part a game-changer.
Christine, thank you for advocating for your dad. Keeping you and your dad in my thoughts.
Thank you so much; I asked our CLL specialist this question, and she provided helpful information about the 5 patients who progressed to RT after venetoclax based treatment: 1/5 had a partial response to EPOCH, 2/5 had a complete response, 2/5 did not respond to EPOCH.
Dad is a robust 66, so we are going to fight this transformation with VIGOR and RELENTLESSNESS. We are still undecided about the EPOCH approach in Philly or the Loxo trial in NYC, but we will have to decide by this weekend because Monday is the start of the regimen. Thank you for insightful response, sllincolorado.
I have b-pll. does your father have b-pll or t-pll- however i am p17 deleted and tp53 abnormal. I cannot use traditional chemotherapy. I bring this all up because i am on ibrutinib/venclexta/ and 6 months of gazyva. at the 2 year mark of diagnosis i have acceptable blood numbers. i have never looked into epoch-because it would not be recommended for me. I agree with others . find out if you can go to another if the other doesn't work.
i did not get the trio initially. venclexta and gazyva were not approved drugs first line at the time. i was a year on imbruvica when my doctor thought it was failing. I wanted to just add venclexta but she said no. I stated venclexta overlapping with imbruvica for 6 weeks then stopped imbruvica . within a month i was .'flaring up again. I insisted on adding imbruvica back. within a few month i had pretty good numbers. then i saw my specialist. she said since i was already on imbruvica and venclexta i might as well add gazyva. so i did. i am not on a trial. I use medicare part d.
My husband is pretty much in the same situation as you. B-LL tp53 de ok eyed. His blood levels are pretty good but the nodes are growing out of control and breathing and eating are now a problem. He too can’t take EPOCH. Is the Gazyva helping? Where in the country are you being treated? Good luck.
Gazyva (first 6 months) helped shrink nodes, but dad progressed with the Venetoclax part of the combination therapy. We are in Philly. Thank you so much for your reply. We appreciate you.
Good luck! We’re in Washington DC. My husband is much older than your father and has the complication of Parkinson’s so we’re really trying to buy time at this point. I’m still searching for a clinical trial but am not optimistic. The docs have now suggested CAMpath. Hang in there.
Although there is some limited data published that shows varied success with both treatments, I have not been able to find any comparative data for Richter's Transformation that measures Loxo vs EPOCH nor have I found any information that provides sustainable prognostics for patients experiencing transformation while using venetoclax.
You may try reaching out to Dr. Koffman at cllsociety.org for information related to venetoclax relapse and transformation, as he may have acquired some insight through discussion with the research community.
I too am very interested in this subject. Please let us know if you find any conclusive information.
I am sorry for that I have no response to help. I am trying to figure out the Cll and melanoma that I was diagnosed with. It is frustrating especially when you don’t know what is the answer. Wishing your dad the very best recovery.
You did not mention your dad‘s medical professional profile, so we can’t know the stream of advice. It would have been good to know if a CLL expert was recommending this or a traditional hematologist, and it would be good to know what hospital or organizationhe was being treated at. All of these would sort of indicate the depth of experience. I think you’ll find that most of the people on this chain are going to avoid a direct recommendation but are going to be able to share their own experiences and also tell you any experiences they have had with the doctors and the organizations your dad is being treated at or by.
I personally know one CLL patient who has managed through Richter‘s transformation and is doing just fine.
There are some incredible videos, by CLL experts, the deal with your questions and they are really amazing. Some are posted here, and many are posted at cllsociety.org
CLL like many cancers is tricky.
Keep your head up, there are incredible advances in the last 10 and five years and there is some very smart people focused directly on Richter's transformation.
Our CLL specialist in NY is offering the Loxo-305 clinical trial, and our CLL specialist in Philadelphia is offering the obinutuzumab-EPOCH-venotoclax approach. Both doctors are highlighted on the CLL Society's list of experts.
My dad was diagnosed with aggressive CLL with PLL and paraimmunoblastic features in March 2020. The first-line treatment was obinutuzumab/venetoclax but after a year on this treatment, his disease has turned to a Richter's Transformation (large cell lymphoma). The transformed disease is concentrated in his right femur (6 cm of cancer), but the concern is it is spreading rapidly because he is now feeling bone pain on his right side, and he is experiencing chills. My dad does not have 17P deletion and no TP53 mutation. However, his IGHV is unmutated, there is no expression of Lef 1, and he has a loss of 3Q and 12P according to FISH analysis.
We can begin either regimen (Loxo clinical trial in NY or O-EPOCH with venetoclax) on Monday--so the time to decide is this weekend. Thank you so much for your care and for the reply that you provided. I will continue our research to provide my dad with the most up-to-date information, so we can make an informed decision--as the CLL Society promotes "Smart Patients Get Smart Care."
Hi ChristineNew to the journey of cll with my husband. Many others on here with sage advice and suggestions. Like you, prayers and well wishes being sent your way for you & your Dad~
Hi, I answered you in the Richters facebook group as well but see some more information here so I can furter add to my answer. As you can see in my profile I have done both these treatments (on Loxo 305 now, waiting to learn what response I have).
Is the Loxo trial with MSKCC in NY?
I was told that there is about 60-70% chance of Richter's responding to Loxo 305. I have no idea what the numbers would be for PLL so this is a question to ask.
But it is likely to have some response, stabile disease or better for CLL/Richters. The % for response increases the longer the patient have been on Loxo 305 (like other BTK inhibitors), ORR went from 65% to 80% with time, this is nice to know when waiting to see what is going on. They have also had patients that reached good enough remission for a transplant if this is the next step. This might be patients with just CLL, but there are evidence of quite good responses. If remission is not reached you can most likely move to EPOCH with Venetoclax.
I would also think that a period without Venetoclax can only be positive in the hope of having a good response on it later (this is purely a speculation from my side!). An important point is also that it is very few side effects, as some other members here can also testify.
EPOCH is often also dose adjusted, it can be a very, very tough treatment. Making the immune system go through this might give a long lasting effect. From my understanding if you can/wish to do a CAR-T later healthier cells that have done less chemo will be positive. It is my personal (subjective) experience that my cells are less damaged from using targeted therapies than they where after going through the chemo courses. I would choose this only if the plan is to go straight to transplant. Transplant can be curative, BUT, transplant will at the moment exclude many clinical trials, so it might be worth looking seriously at other available trials first such as CAR-T and bi-spesific antibodies. This is a discussion to have with the doctor.
If you wish to go this route of Chemo to try to "knock it out" it might be an idea to look for a trial that combines it with a different drug than Venetoclax (such as a BTK inhibitor) since he already progressed on it. I believe I have seen EPOCH combined with Acalabrutinib in a trial (possibly posted by someone in the Facebook group), but you can reach out to LLS, they have specialist nurses that are Amazingly helpful in finding trials. I found establishing the help of the clinical trial team at LLS was very helpful!(!!) If your father enrols in Loxo305 trial it seems to be about 60-70% chance that he will have time to find such a trial or (maybe with the help of LLS) find other suitable options.
The Loxo 305 trial have also been running for a while, so it is a valid question to ask if it would be still open after an eventual EPOCH / Venetoclax (or other targeted drug) trial/treatment. My doctor indicated that I was lucky that I could still enrol about a month ago.
This is just my personal opinion, based on some personal experience.
I’m so sorry to hear about your father. My husband is in a similar situation. His CLL transformed into PLL. He too tried the drug combinations but due to his physical condition (he’s very weak) he would not survive Chemo or CarT cell therapy. His doctors have suggested his best option is the thrice weekly infusion of CamPath to buy us more time and is not as tough on the body. Would you mind telling me where your father has the option of getting Loxo 305?
We’re looking for any and all PLL trials or drug options.
Wishing you and your father much luck. Stay positive and know that many people are sending you positive energy and prayers
Like you I have found this group to be very helpful. Thank you all! Nina
They’re wonderful but couldn’t help. If you’re open to speak with me I would be most appreciative. We’ve been told by our CLL expert that we have few choices. Thank you so very very much. This group has helped me feel less alone during this battle. Nina
Great news! They do have a cohort for B-PLL in the LOXO Bruin 18001 study. I am not sure if your husband will qualify and where the closest location is but you can reach out to them. I will message you with the details.
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