Hi,
Venetoclax in combination with obinutuzumab has been approved frontline for CLL. This is the first fixed duration non-chemo approach for CLL. For more on this important development, please see: cllsociety.org/2019/05/fda-...
This is a big deal.
Brian
thanks Dr Koffman, does this mean that the combination treatment can now be offered through all insurance coverage or is there typically a lag between FDA approval and insurance coverage?
A very big deal! Thank you,
Thank you, great news
One step at a time. This is a big one!.
alpek Hopefully insurance companies will see this as a better option than long term use of these newer, and very expensive, drugs.
MsL,
I agree. The time limited duration however is based on your response I thought. MRD = cessation. How was it approved?
Jeff
Thanks so much, Dr. Koffman, for sharing this important news. I’m treatment naive and supposed to begin Ibrutinib treatment in two weeks. I do have an appointment with my CLL doctor on May 29. May I ask what you will be recommending for your patients in my situation?
Brian (Dr. Koffman) is a family practice doctor. Even a CLL specialist could not suggest a particular treatment or when to begin treatment for a patient without knowing about that patients particular case, as well as what is available in their country. Which drugs have been approved varies from country, and province to province in Canada.
I’m glad ibrutinib is available to you. It has worked very well for many. Several people on this forum are taking ibrutinib and can tell you about their experiences with it. Start a new post with ibrutinib in the title to catch their attention. You might want to give some information about your CLL. If you lock your post you usually get more replies. At the bottom of the post change the setting from everyone to community only to do that.
And he’s also retired now. He’s just focusing on himself and us now.
Thanks very much. I have recently posted about myself and my imminent Ibrutinib treatment. It was so wonderful to get many responses from others who shared their Ibrutinib experiences. I look forward to seeing what my CLL doc will say about the newly approved V+O option.
TT,
Being treatment naive and about to embark on treatment, there are many options.
That said, in particular to Ibruntinib or V+O, much is known about how well Venetoclax works following ibrutinib failure. Not much is known on the reverse.
Jeff
Thank you. That really is an important consideration!
First, I am not a doctor, so please take this with caution.
Concerning the recent approval of venetoclax+obinutuzumab for first treatment of CLL, I would ask the following questions to my CLL specialist. 1) Is obinutuzumab really needed? A retrospective study published in Blood Advances suggests it may not, same as for rituximab added to ibrutinib: it may not add much). Obinutuzmab is more powerful than rituximab and seems to have stronger AE as well. 3) If needed, does it matter whether you start with obinu first and then add the venetoclax (with ramp up), or do it concomitantly, or after a few months on venetoclax? 4) Is it better to keep venetoclax as a back-up for eventual relapse and start with, say, acalabrutinib (seems safer than ibrutinib)? 4) A significant fraction of patients develop venetoclax resistance, but I do not know much about this.
Yes, it is great news, but we do not know much about long-term effects, optimal sequencing, etc., yet. Advances are being made at a great pace, but crucial clinical trials on combos may not produce meaningful results until 2-10 years from now.
I really appreciate your thoughts on this. These are all excellent questions, and I will add them to my list for next week’ s appointment. I was also thinking that Acalabrutinib would be a better alternative to Ibrutinib. Lots to think about!
Acalabrutinib hasn’t been approved for treatment of CLL, just Mantle cell lymphoma. It can be prescribed off label by your Doc but insurance may not cover it and at around $12k a MONTH, that’s not good.
Jeff
Motoli,
Please post that Blood Advances article you referenced. I’m aware of the studies show Rituxan not adding anything to ibrutinib but the opposite I thought was true for Venetoclax and expected obinutuzamab to be better.
Are you certain of this?
Jeff
The paper by Mato et al. (2019) is in bloodadvances.org/content/3...
It concludes as follows:
"We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings."
Please read the paper carefully for the definition of VENcombo. The combo refers to anti-CD20 and, when I read the paper, I thought it referred to either rituximab or obinutuzumab.
Ah, the Devil is in the details,
“We hypothesize that our cohort, which may reflect current VEN use in clinical practice, likely contains a higher proportion of anti-CD20 refractory patients. This may explain the observed lack of benefit for the anti-CD20–containing combination over VENmono. This analysis provides a hypothesis that adding anti-CD20 antibodies to VEN in heavily pretreated patients may not improve clinically relevant outcomes.”
This study is not relevant for treatment naive or perhaps once treated in my opinion.
JUST MY OPINION.
Jeff
It was my understanding the obinutuzumab would decrease the tumor burden before Venetoclax would be introduced into the regimen and hence would decrease the chance of tumor lysis syndrome. Please correct me if I'm wrong (I don't recall where I read this),
Correct for treatment naive or lightly treated. Obinutuzamab doesn’t work in CD20 refractory patients. The target has already been eliminated.
What does "CD20 refractory" mean?
Yes, but the anti-CD20 refractory cohort matter is just a hypothesis. Actually, Mato et al. add: "This analysis provides a hypothesis that adding anti-CD20 antibodies to heavily pretreated patients may not improve clinically relevant outcomes". Further, Mato et al. at the end state that "it is imperative to include monotherapy control arms..."
From what I have read, the inhibition of anti-CD20 by, say, ibrutinib, is still a hypothesis.
Of course, the situation may be completely different in treatment naive-patients.
Also, what is "frontline" versus "second line"? Sorry, this must be pretty basic but I'm getting confused. Aren't we talking about V+O for frontline therapy?
That question should be referred to a CLL specialist. My understanding is that anti-CD20 is included because it helped immunochemotherapy in the past. The view seems to be changing in the light of novel agents such as ibrutinib or venetoclax.
I do not think that obinutuzumab was added with the explicit purpose of reducing tumor burden as that seems to be achieved satistfactorily by dose ramp-up. Rather, (I think), the objective was to "sinergize" and help to attain minimum MRD.
Any doctor in town (:-))
Thanks Motoli. I think I'm in over my head. These discussions seem to start simply enough but then they morph into other topics that keep going deeper and deeper into a myriad of possibilities that I can't keep straight. I'm beginning to think that maybe I should stay away until there are more definitive findings.
That’s called watch and wait 😆
You're right! But I'm getting close to being treated and just want to have a clear understanding of the current options available. There are so many conflicting opinions from different doctors and specialists. It's difficult because this is not a "one size fits all" disease.
Your options depend on your current health and your blood test results. Pick the best doctor that you trust with your life and if you don’t clearly agree, get another opinion.
You should be getting your clear understanding of the current options available to you from them.
There is no correct answer, if there was, I’d be doing it as I will be getting treatment soon too.
Jeff
Thanks - good luck.
Thanks so much Dr. Koffman. Do you know if this combination is accepted for second line treatment in the U.S?
Obviously, I’m not gonna speak for Dr Koffman but you might be able to get it prescribed off label as both drugs are approved for CLL but that combo for second line is not. Insurance might not pay.
Venetoclax and Rituxan is approved currently for second line.
Jeff
Thanks Jeff!
I suspect it could be obtained but the benefits of adding G to V is not clear in R/R patients.
Thanks Dr koffman.
Good point on duration . Doctors in the USA hopefully prescribe this combo instead of FCR or BR now.
Drug costs can be a factor but this is a clearly better treatment than FCR.
Be well,
Hoffy.
Hoffy: I’m not certain how you can say V + O is a better treatment than FCR for certain segments of the patient population such as treatment naive patients who are mutated. Many, but not all, CLL Specialists would disagree with you on this point. You really need to be careful about statements like these.
Best
Mark
Furman was at the forefront of no chemo for no body - even younger healthier cohort with favorable markers (he's your doctor and you want chemo, he'll say get a new doctor). One by one, year by year more have joined him given the overall safety and effectiveness of the new targeted therapies. But many, likely a majority, of CLL Experts would still agree with you.
Agreed
FDA APPROVAL FOR ZANUBRUTINIB
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Venetoclax Approved!
A071402 Phase 3 clinical trial - Obinituzumab+Ibrutinib+Venetoclax
CALQUENCE gets FDA approval for treating CLL
