“My myeloma is stable. How long do I need to stay on maintenance therapy?”
This is the million dollar question for nearly all multiple myeloma patients at some time during their myeloma journey.
More and more articles like the one below nudge us toward the decision to stay on maintenance indefinitely. Give it a quick read and I’ll meet you on the other side:
Lenalidomide Maintenance After Stem-Cell Transplantation Benefits Patients With Multiple Myeloma
Jill SteinPublished Online: Friday, August 31, 2012
The immunomodulator lenalidomide (Revlimid) used continuously after autologous hematopoietic stem cell transplantation significantly prolonged the time to disease progression and overall survival in patients with multiple myeloma compared with placebo, according to the results of the phase III CALGB 100104 study.
Maintenance lenalidomide is, however, associated with increased toxicity and second primary cancers.
“This study suggests that lenalidomide maintenance therapy until disease progression is feasible for long-term use,” Philip L. McCarthy, MD, director of the Blood and Marrow Transplant Program at Roswell Park Cancer Institute in Buffalo, New York, and his co-authors wrote.
Investigators at 47 centers randomized 460 patients with stable disease or a marginal, partial, or complete response 100 days after undergoing a single stem-cell transplantation to maintenance lenalidomide (10 mg daily) or placebo until disease progression.
Multiple myeloma is largely incurable, and disease relapse/progression is the primary cause of treatment failure after high-dose autologous stem cell transplantation, the authors noted. Maintenance of a prolonged progression-free interval with minimal toxicity is an important objective in managing this disease.
The primary endpoint was time to disease progression, defined as time to progressive disease or death from any cause after transplantation.
The study was unblinded in 2009, after a median follow-up of 18 months, when 47 of 231 lenalidomide-treated patients (20%) had progressive disease or had died versus 101 of 229 placebo-treated patients (44%; P <.001). Of the remaining 128 patients who received placebo and did not have progressive disease, 86 crossed over to lenalidomide.
At a median follow-up of 34 months, 86 of 231 lenalidomide-treated patients (37%) and 132 of 229 placebo-treated patients (58%) had disease progression or had died. The median time to progression was 46 months and 27 months in the lenalidomide and placebo groups, respectively (P <.001). Overall, 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P = .03).
The lenalidomide group had a higher rate of grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events (P <.001 for both comparisons).
Of the 231 lenalidomide-treated patients, 8 (3.5%) developed new hematologic cancers and 10 (4.3%) developed solid-tumor cancers. Of the 229 placebo-treated patients, 1 (0.4%) developed new hematologic cancer and 5 (2.2%) developed solid-tumor cancers. The increase in second primary solid-tumor cancers in patients treated with the immunomodulator was not associated with a specific tumor type, and potential causes for the increase have not been clarified, the authors pointed out. They recommended close monitoring of blood counts and standard screening for cancers.
Finally, they said that future research is needed to determine whether combining other new agents with lenalidomide will further extend the time to disease progression and overall survival.
McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1770-1781.
I didn’t see any overall survival (OS) statistics there, did you? Yes, fewer patients died while on maintenance:
Overall, 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P = .03).
That’s an 8% advantage for the maintenance patients. But did you notice that almost 8% of patients on maintenance developed a secondary cancer?Less than 3% of patients not using maintenance developed secondary cancers.
There is no discussion about quality of life issues, except that:
The lenalidomide group had a higher rate of grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events (P <.001 for both comparisons).
And what about the high cost of taking years one or more maintenance drug for years?
So as you can see, the answer to the question, “How long do I need to stay on maintenance therapy?” is a complicated one. A majority of hem/oncs would answer, “Indefinitely.” At least that’s what one needs to do in order to gain the significant time to disease progression benefit outlined in studies like the one above.
At this point, readers often ask: “How can using maintenance therapy keep my myeloma away for almost two extra years, yet in the end not help me live much longer?”
Great question! I will attempt to answer it tomorrow.
Feel good and keep smiling! Pat
September 4th, 2012 at 11:16 am
Did the study compare patients by low/high risk groups? I can see where maintenance would have an advantage in high risk cases, but not so much in low risk.
Million dollar question….for us maybe, but billions of dollar question for pharma. I know you can’t place a price on human life. But for me, unless there is a clear cut case the maintenance would have helped for me(low risk), I can’t spend the money–even if it is my insurance paying the bill. Healthcare cost are out of control, and it starts with me doing my part. Of course, going four years post auto transplant helps that attitude.
The problem with maintenance is the side effects. I would love to hear from your readers that are on maintenance and if the side effects really are or aren’t an issue. What about readers that have kidney issues like I do, how does that affect them with Revlimid?
Looking forward to this series, Pat. When so many great minds don’t agree, it is good to see the reasons why. Grateful so many doctors are working so hard to help us.
I should add, I am kind of different. I don’t fear death. I love life. But, I believe there is a time to be born and a time to die. And cancer does not change that time for me to die….it is just the method it happen. That gives me great peace. It takes away the power of the cancer.
September 4th, 2012 at 12:21 pm
Very profound, JC! I like the line “takes away the power of the cancer.” I agree with that! I believe all patient types were mixed-in together. And maintenance seems to work well in both low and high risk patients – even better in low risk patients. Total Therapy keeps patients on maintenance for at least three years after they achieve CR. It’s an arbitrary date. We may be decades away from really pinning down the answers to these questions. Tune-in tomorrow. Hope I can shed more light on all of this…
September 4th, 2012 at 2:00 pm
Pat: I am looking to answers to this question not only for those following a transplant but for us elderly and frail types who jump right to maintenance following consolidation. I hope you will also address the issue of becoming refractory to maintenance agents. Shouldn’t we be saving their use until needed?
How about dosage regimen. It seems to me that in the past you decried the three year maintenance period at UAMS. Have you changed your perspective?
September 4th, 2012 at 2:23 pm
Of course, Gary! Maintenance isn’t just for post SCT. These stats apply to any myeloma survivor who has their myeloma currently under control. I will address your other questions tomorrow, too…
September 4th, 2012 at 3:43 pm
Pat, I’m still waiting better evidence that shows Rev will lengthen your life by more than just a couple of months. I don’t find that a compelling reason to start maintenance chemo with all of the side effects. Especially with the kidney failure that I have. I would rather live symptom-free and side-effect free for as long as possible before starting treatments again.
Also, if you could put me in touch with JC, I would love to chat about MM and kidney issues!
September 4th, 2012 at 3:50 pm
Hopefully JC will respond. If I hear from him via email, I’ll definitely try and get you two together. Are you going to be at the support group meeting in Spokane on the 17th. I’m flying-out to speak…
September 4th, 2012 at 3:52 pm
Hi, Pat, I am addressing JC’s above comments. I’ve been on Revlimid maintenance (5mg 21on/7off) maintenance for two and a half years – began one year after ASCT. I’m at M.D. Anderson and see the nephrologist on my team every six months (kidneys are at 35%.) I was on 10 mg Revlimid for awhile; however, the kidneys couldn’t handle it. The side effects are sleepiness, fatigue, leg cramps. I have fairly severe neuropathy, but blame the Velcade and Thalidomide at induction, not the Revlimid.
September 4th, 2012 at 3:58 pm
Revlimid aggravates my PN, Beth. Funny how differently we all react to medications, isn’t it?
September 4th, 2012 at 7:11 pm
Pat, no I won’t be at that meeting. Spokane is a little far for me. Maybe one day you’ll speak in Boise, or somewhere a little closer. I look forward to meeting you someday!
September 4th, 2012 at 8:41 pm
Pat, I think the main point of the article was this:
“The study was unblinded in 2009, after a median follow-up of 18 months, when 47 of 231 lenalidomide-treated patients (20%) had progressive disease or had died versus 101 of 229 placebo-treated patients (44%; P <.001)."
And while one can argue that OS wasn't terribly fantastics compared to the placebo (and not including side-effects and increased secondary cancer), it is still quite a significant difference.
That statistic (increased time to disease progression but NOT overall survival) is the thing that constantly haunts me on a daily basis. It just SHOULDN'T BE! One should follow the other, and it's possible it is (on a patient by patient standpoint rather than the whole), but the trend does tend towards the "you're damned if you do and damned if you don't"….
September 4th, 2012 at 9:26 pm
JustinS: I wouldn’t let medians haunt you. In the non lenalidomide arm most of the patients may have died in the first nine months. Also, the 54% that were still living after 18 months might have lived for five more years all free of the side effects of lenalidomide. We need to get better data before we can make informed decisions for ourselves.
There is a new procedure being rolled out by medical researchers called adaptive clinical trials. In this procedure you are your own control. You start treatment with a standard dose of lenalinomide and within a very short time period “adapt” the dose to maximize the containment of the MM and minimize your toxicities. Then you can decide whether or not to continue with the treatment for a personalized QOL. Every few months you can then revisit your decision.
September 4th, 2012 at 11:46 pm
Sheri-
If there’s a support group down there, get me the contact info and I’ll see what I can do!
Justin and Gary both make good points. “Adaptive clinical trials” sound intriguing. Lots more flexibility for patient and docs. And Justin, this study summary is just one of many emerging. And why not? Big bucks for big pharma if we all stay on maintenance for half a decade or more, right? That shouldn’t reflect on the results–simply the motivation to do so many maintenance studies! Which has always confused me why Millennium didn’t jump on the maintenance bandwagon sooner. I am having a heck of a time finding any consensus over how much Velcade to take–and how often–for my post relapse maintenance regimen…
September 6th, 2012 at 9:54 am
Pat, excellent discussion, I especially liked JC’s.
your comment of: So as you can see, the answer to the question, “How long do I need to stay on maintenance therapy?” is a complicated one. A majority of hem/oncs would answer, “Indefinitely.”, makes me think of a phrase that ‘many doctors treat the disease and not the patient’. my local oncologist fault me tooth and nail to stay on maintenance ‘indefinitely’, but the specialist agreed with me that a stable condition has earned a holiday from treatment. he believes in treating today’s condition, not in treating what may occur. nobody knows and quality of life is more important than a few extra months.
going to Dallas tomorrow for my first event
jim
September 6th, 2012 at 11:48 am
Good luck, Jim! How exciting! And glad you are taking a drug holiday. I think you will see more and more docs disagreeing over maintenance issue…