Multiple Myeloma – 1st Line

Posted by Jeff Berk, BOLT International;

 

The cave dwellers of the land that we now know as England had rather unsophisticated lingual skills.  Short guttural sounds were used to convey long, complex meanings.  One of these sounds, “nan” meant “blows hot and cold, for no reason that a man could possibly comprehend”.  A typical sentence that the cavemen might use was “She’s up to her old shenanigans”.  We also see “nan” used in modern English.  For example, consider the phrase “nanny state”.  Here it’s the State, once again female in gender, that blows hot and cold for no reason that a man could possibly comprehend.  Where’s this going, you might ask?  Well, since YOU asked about the Nanny State, this blog is going to say some un-nice things about NICE, the Orwellian named Nanny State group-stink descended directly from the very same cavemen I cite earlier in my diatribe.  NICE has single-handedly proffered more stupid edicts than all other Death-Panels on Earth, and she was up to her old shenanigans this week.  So here’s the most recent “cost of replacement is cheaper than cost of repair” pronouncement from NICE:

 

 

UK Body Backs Thalidomide And Velcade in Multiple Myeloma

(Note:  the title isn’t the problem.  Or wouldn’t be if NICE were actually backing the combination (+ dex) as 1st line.  Or other better combinations for 1st line.  But they’re not.  Read on)…

Jun 16, 2011 19:06:19 (ET)

LONDON (Dow Jones)–Britain’s healthcare cost-effectiveness body Friday said it recommended publicly-funded use of Celgene Corp.’s (CELG) thalidomide and Johnson & Johnson’s (JNJ) bortezomib on the National Health Service for treating a type of bone marrow cancer called multiple myeloma.

The National Institute for Health and Clinical Excellence, or NICE, said in a statement it was provisionally backing thalidomide in first-line treatment of multiple myeloma in people for whom high-dose chemotherapy with stem cell transplantation is considered inappropriate.

NICE also backed bortezomib, whose brand name is Velcade, in combination with an alkylating agent and a corticosteroid for first-line treatment of multiple myeloma if high-dose chemotherapy with stem cell transplantation is considered inappropriate and the person is unable to tolerate or has contraindications to thalidomide.”

Carole Longson, Health Technology Evaluation Centre Director at NICE said in a statement: “The evidence clearly showed that both thalidomide and bortezomib regimens are more effective at delaying disease progression and improving patients’ life expectancy than the current treatment of an alkylating agent and corticosteroid alone.”

“The two regimens were similar in terms of clinical effectiveness, but thalidomide regimens were more cost effective. However, bortezomib has been recommended as an option for people who are unable to take thalidomide as it was considered an appropriate and cost effective treatment option,” she said.

NICE said a final decision on the subject is expected in July.

 

 

 

Okay, look.  The only, and I mean ONLY, reason NICE is pushing thalidomide for its Death Panel patients is that they are to damned cheap to pay for Revlimid + Velcade + low dose dex.  And the notion that bortezomib and thalidomide are equally effective in 1st-line not eligible for transplant is, as they say in English “a stretch”.

 

 

 

 

 

 

 

Hey, Ms. NICE, if you don’t want to pay for Velcade, then (according to some of BOLT’s Myeloma Thought Leader Panelists, Revlimid (+melphalan + prednisone) is the other 1st-line therapy of choice for younger transplant ineligible MM.

 

 

 

Here are a few thoughts from our panel…

“I do think the majority of people would favor using Velcade in newly diagnosed patients.  I do think that many people are choosing to go with the combination of Velcade and Revlimid, certainly in the United States.  Outside of the United States that is a very difficult economic proposition and I think Velcade is probably the favorite.  I don’t know if the marketing backs it up or not but that is my sense.  So Velcade I think has still got a dominant hold on the popular imagination for newly diagnosed patients.  Then there is certainly a lot of Revlimid use as well, particularly in countries like the US where you can get both together”.

 

“I think lenalidomide in combination with melphalan and prednisone could be and probably will be one of the standards of care in patients who are not candidates for transplant”.

 

“From my standpoint it doesn’t really change practice because I practice with maintenance.  I think before we had enough data to proceed with maintenance.  The question was always what kind of maintenance?  First, maintenance treatment was actually established by a SWOG.  It was almost 15 years ago, Jim Berenson’s study which showed that prednisone if you are able to give up to three years will improve survival.  And then came a British study with interferon, which was not really, I think, an attractive study because nobody can go with long interferon.  And then came thalidomide.  There were definitely several European studies with maintenance with thalidomide with or without transplant and then Bart Barlogie did total therapy 2 and then total therapy 3, which showed that patients who received thalidomide maintenance actually live longer.  The problem with the thalidomide maintenance is that when they relapse after that they live shorter than patients who did not get thalidomide.  And that is the problem that I have with thalidomide.  Maintenance with Velcade is also I think becoming very popular and in my practice I use it.  Of course, maintenance with Velcade goes once-a-week which now is becoming more and more a way to give Velcade because of Palumbo’s study showing reduction in neuropathy.  Maintenance with Revlimid I think will become a little bit more complicated because of its hematotoxicity.  So I think maintenance with Revlimid needs to be figured out dose and schedule”.

 

“I think the myeloma theme came out pretty clear that a) maintenance is going to be important because then you have the non-transplant study, Palumbo’s study, where he did the Revlimid maintenance followed a non-transplant and that the people getting Revlimid maintenance are doing better.  I think that just tells you that even for the transplant and the non-transplant candidate prolonged therapy with Revlimid is going to be important.  That I think is one big take home message that we are still trying to fit in.  Particularly what to do with the patients who are being transplanted now?  You wonder what are we going to do with all those patients who got transplanted and are one-year out of their transplant?  Are they going to go back to their physicians and say I want to go on Revlimid?  It is going to be interesting to see what happens”.

 

“I think (carfilzomib) is going to get used up front and then eventually it will probably be used in the maintenance setting.  So you are saying it is going to displace bortezomib up front? I would say, well actually, if you had asked me last year I would have said yes, but now with the idea that with changing bortezomib dosing you can get away from the neuropathy and still get the efficacy it might be a whole different story.  So the critical thing there is do you believe that once weekly bortezomib…? I think it is.  Its close; it is good enough for government work”.

 

“Is everybody going to move to bortezomib once weekly? No, I don’t think so.  I think the bortezomib twice weekly will remain a key platform.  I think bortezomib will remain the first choice proteasome inhibitor.  I think the new boronate peptides coming through the pipeline are very interesting.  I think carfilzomib will be approved and will be a widely used proteasome inhibitor, but I think it will be used in the context of bortezomib intolerance and/or bortezomib failure.  I will be surprised if it knocks bortezomib off of its perch.  At the end of the day myeloma patients who walk in the door who are sick as stink and need three drug therapy are typically metabolically ill.  They will have renal failure and will have all these other issues.  You want a drug that is going to work that you have a very clear understanding of the toxicity profile”.

 

“There was, I think, a remarkable study that basically contrasted and compared various induction approaches in the European context.  I think these are not necessarily combinations that would be first choice in the US.  There are some important lessons to be learned from them.  Maria-Victoria Mateos in a randomized prospective fashion I think pretty convincingly showed that a proteasome inhibitor with an alkylator as induction followed by an IMiD, if all you have is thalidomide, is the way to go in her randomized trial.  So you had a randomized trial in older patients where she compared various regimens, showed that thalidomide plus Velcade plus steroid induction therapy in the elderly was very active but not particularly well tolerated.  She showed that VMP was better tolerated”.

 

 

“Celgene is trying to give a role to pomalidomide as basically third…farther agent in patient’s resistance to lenalidomide.  This is the role of pomalidomide.  Pomalidomide is a little bit more effective than lenalidomide.  That has some other side effects like hematologic toxicity but I think what will be very much the use of pomalidomide will be, again, in those kind of niche that we were talking about before for carfilzomib and HDAC inhibitor this would be the perfect agent to use if you want something or in condition where lenalidomide is already completely resistant.  Probably with time pomalidomide will move early on.  Honestly speaking, I am not looking also at the data.  Some people are saying, well, pomalidomide is completely different, and in my opinion if you look at the efficacy lenalidomide stays at thalidomide as pomalidomide stays at lenalidomide.  So every time you increase the efficacy a little bit with the novel agent but you are not really changing the world because you are not doubling the CR rate where basically increase of 15 to 20 percent, a response rate with the newer agent.  So the efficacy is not changing the world.  It is better but it is not dramatically better and that this is the perfect agent and I think Celgene will do everything possibly to position that agent in that respect.  It is the perfect agent to use in lenalidomide resistant patient”.

 

“I think pomalidomide in a lenalidomide world is huge because I think what you are going to see is that lenalidomide is used up front and in truth the pomalidomide will start to go right into lenalidomide failure where as thalidomide currently will sort of increasingly get pushed sideways.  Pomalidomide is awesome.  It is quite frankly in my experience the best of thalidomide and the best of Revlimid put into one to be perfectly honest with you”.

 

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