[kdaneedgar]

Great response to Kyprolis, Revlimid & dex: what next?

by kdaneedgar on Tue Jul 12, 2016 12:23 pm

I was diagnosed in March 2016 with Stage 3 multiple myeloma. I was symptom free and my disease was caught as doctors checked into my anemia. I have t(4,14) as the main culprit.
No bone issues and no kidney problems. Basically, a perfectly healthy 56 year old, except I had cancer.

Did you catch the past tense "had"? I was 50% cancerous plasma cells when diagnosed. I started on the E1A11 study in mid-April 2016. This study is trying to get Kyprolis approved as a 1st line drug, rather than as a drug to use after other treatments. The participants are randomly put onto either Velcade or Kyprolis (plus Revlimid and dexamethasone for both). I lucked out and got into the Kyprolis arm of the study.

After 3 cycles of chemo, I had another bone marrow biopsy and it came back completely clear!
No cancer cells of any kind, 1.6% plasma cells (within the normal range) and all of them are normal. Please allow me to say it was miraculous! I know, everything I read says to plan on your multiple myeloma coming back. But is that always the case?

Has anyone else experienced this type of reversal with Kyprolis or any other drug? Has your multiple myeloma remained in remission?

Now I don't know what to do. I'm going to have stem cells harvested in July, but not have a transplant. Of course my transplant doctor is against this, my multiple myeloma doctor is more in agreement with me, but not 100% positive. I also don't know what do do about the E1A11 study. It calls for 6 more cycles of chemo. But do you continue to take chemo after complete remission, or do you go onto maintenance with Revlimid and dex, or do you do nothing but monitor?

I meet with my multiple myeloma doctor in a few days, so I hope we resolve some of these issues.

Any views or personal experience would be so welcome.

[kshornb]

Re: Great response to Kyprolis, Revlimid & dex: what next?

by kshornb on Tue Jul 12, 2016 4:00 pm

Hi kdane:

It is truly wonderful how you have responded to your treatment, and I am so very happy for you.

I feel that I need to respond to your post, but I want to be extremely careful with my words, and not portray my experience as typical for multiple myeloma patients or even similar to yours. The more I learn about people with multiple myeloma, the more it seems that there are no 2 of us that are identical.

I was diagnosed in July 2015, after a trip to the emergency room. I thought that I was having a heart attack or a stroke (because of the pain in my chest, and a momentary loss of memory and confusion). It ended up that the pain in my chest was a plasmacytoma, I never required radiation on the cytoma, which was wonderful. They never specifically identified the cause of my memory loss or confusion, I think it was probably from the fear of not knowing what was going to happen.

Once they had completed a battery of tests; bone marrow biopsy, PET/CT scans, MRI's, x-rays, multiple blood tests, it was determined that I had multiple myeloma with multiple bone lesions, rib fractures and 3 compression fractures in my T6,11 and 13 vertebrae. There was 60%-70% plasma cell involvement, and I was also positive for del 13(q), under FISH. However, I had no other issues (high proteins, or kidney involvement). I have lambda light chain Myeloma, and am considered to be at standard risk. There was some disagreement among my doctors as to whether I was stage 2 or 3, but I decided that it wasn't important to me to know, because it really wouldn't affect any of my treatment decisions.

In August I started on Cytoxan (cyclophosphamide), Velcade, dexamethasone weekly, and Zometa once a month for my bones. According to my blood work (light chains), I achieved remission in 3 months. However my oncologist wanted me to stay on the treatments for another 3 months (which I understand is typical protocol). I followed his recommendation, and once the entire course was completed another bone marrow biopsy was done, and like you, it showed that I had less that 2% plasma cells and all were normal. I had achieved complete remission (CR). At that time I was referred to the stem cell specialist to discuss a stem cell transplant.

I had the same questions as you, why should I have the stem cell transplant if I was in remission? The way that it was presented to me was that they preferred to do the stem cell transplant when I was in CR, for a couple of reasons:

1. They typically have a better long term response, when you are in CR.
2. They told me that they cannot guarantee that they could get me back in remission, if I relapsed, to then do the stem cell transplant.

I would not attempt to give you advice as to whether you should continue chemo or not, or whether to do the transplant or not, it is most certainly a decision you have to make with your doctors, however what I have learned through this forum, and other research I have read, never underestimate this disease. It can sneak back up on you quickly, and trying to catch up can be a challenge. I chose to have the stem cell transplant (May 13th). I was determined to try and kill it off as much and as hard as possible.

There are multiple myeloma patients who have been in remission for long periods of time (20 years+), and I hope that everyone with multiple myeloma today will be able to achieve that length of remission. I truly believe that with all of the new medications, and treatments, combined with the outstanding research that is being done, that there will one day SOON be a cure.

I have my first bone marrow biopsy after stem cell transplant Friday, so I am hoping that my results have not changed from before the stem cell transplant .

Best of luck to you with your journey.

Kathleen

[JPC]

Re: Great response to Kyprolis, Revlimid & dex: what next?

by JPC on Tue Jul 12, 2016 5:05 pm

Hello Kdane:

The historical answer for t(4;14) is that you need the autologous stem cell transplant (ASCT). Recent data (not a huge data set yet) is that Kyprolis induction will mitigate, maybe completely, the adverse impacts of the t(4;14) abnormality, and possibly bring you near or into the "standard" risk category. This I think would be a best case. Historically, as you probably know, t(4;14) has quick relapses.

I am not sure if your aspirate was checked for minimal residual disease (MRD). I would suggest asking that of your doctor. About half of the people who reach CR are MRD+, and perhaps need more rounds of treatment.

My wife did reach CR and MRD- on Kyprolis, Revlimid, and dexamethasone (KRD) consolidation, after an ASCT, and we then decided to go into a KRD maintenance phase. I am glad you got there faster. I do not think that there are any clinical trials yet to guide your choice. The somewhat older approach would be to go with the ASCT due to the t(4;14) presence. We are sticking with the KRD maintenance phase. In your case, I of course do not know for sure (probably the doctors don't either). However, I would think it might reasonable to consider the approach of ASCT on first relapse as a viable option, IF you are MRD-.

[rick]

Re: Great response to Kyprolis, Revlimid & dex: what next?

by rick on Tue Jul 12, 2016 7:48 pm

Hi kdane,

My husband was diagnosed in late November 2015 and is also t(4;14). He was ISS Stage 1 but Durie Salmon 2 with some boney disease and 30% plasma cells. He had developed boney pain 8 weeks before his diagnosis.

Our specialist lobbied for early Kyprolis, Revlimid, and dexamethasone (KRD), as he had some neuropathy before treatment and during a single month of Velcade, and based on earlier studies on higher dose KRD combinations. The treatment regimen was approved.

He was also biomarker (M-spike and light chain) negative before the 3rd of 4 cycles. He had 0.25% plasma cells on his bone marrow biopsy in late April before his stem cell collection in May. It later came back minimal residual disease (MRD) negative.

We asked many of the same questions you are asking and, unfortunately, even with the negative MRD test, our specialist didn't feel a myeloma patient could be considered cured so early in his treatment. Perhaps someday, with the great response you are having(!), but not yet. He favored what we are now doing and planning. We had an autologous stem cell transplant (ASCT) on June 3rd and will start KRD consolidation in September.

We thought about just continuing the KRD for 6-8 cycles but in the end went with our doctor's plan for us. We really want a long disease-free period and hope for a cure that these deep responses may represent. Our decision was not easy and I do not envy you with yours.

Our specialist thinks that a cure may be in the offing for patients (like you) who have the best responses to KRD, but that the studies on this are still a few years out. You are in one of them!

I know of no clinical trial to aide in this decision and doubt many Kyprolis patients or specialists have enough time with the medicine to help guide you. This medicine was approved for advanced myeloma patients in July of 2012 and relapsed patients in July 2015. We're in a small subset of the myeloma population using it for new onset induction.

So we continue with the plan.

In standard cancer care it takes 5 years without any disease before a doctor will say a patient is "cured". In myeloma, historically, even 5 years is not considered long enough.

I'd second that you ask about MRD testing and familiarize yourself with it before you make your own decisions.

Wishing you the best response and strength and confidence in your own decisions.

[Chris M]

Re: Great response to Kyprolis, Revlimid & dex: what next?

by Chris M on Tue Jul 12, 2016 9:53 pm

Hi KDane,

I'm very glad you've had such a great response to Kyprolis, Revlimid, and dexa­metha­sone (KRD) and truly hope that it lasts a long, long time! Since you asked for others' KRD ex­peri­ences, I'll share that of my husband, who was diagnosed in 2011 at the age of 59. Please remember that everyone's myeloma is different and you might not have similar experiences down the road. Someone else wrote each person's myeloma is like a unique snowflake, and that seems appropriate to me ...

Other than fatigue, my husband had no other obvious symptoms prior to being diagnosed. We later learned he had 83-85% plasma cells in his bone marrow, either 5.1 or 4.9 g/dL M-spike depending on two different labs that ran the test, numerous lytic lesions (but no bone pain), high creatinine indicating kidney impairment and low hemoglobin indicating anemia.

He was offered a place in a 24-cycle clinical drug study for newly diagnosed multiple myeloma patients: carfilzomib (Kyprolis), Revlimid, and dex. The cycles followed current protocol (3 weeks of infusions consisting of 2 consecutive days, one week off) for 8 months, then bi-weekly infusions for 2 consecutive days through 24th cycle. Revlimid was taken for 21 days with 7 days off. Between cycles 4 and 5, he had his stem cells collected and stored, although he did not want to go to transplant at that time. By the end of the 24th cycle (April 2013), his M-spike was still detectable but too small to quantify. A few months afterwards, no monoclonal protein could be detected and his bone marrow biopsy did not detect any plasma cells.

Starting in May 2013 after finishing the KRD, he took Revlimid and dex for maintenance. Until December 2014, no monoclonal protein could be detected, but starting in January 2015 it began appearing very slowly and in very small amounts – it only increased one-tenth of a g/dL at a time, usually every other month. Nothing too worrisome looking at it month-to-month, and he continued taking Revlimid and dex.

When my husband experienced a DVT and numerous pulmonary embolisms in both lungs in December 2015, we agreed with his hematologist that it was time to change drugs. Despite taking Cytoxan and Ninlaro for 3 months, his M-spiken continued it's slow but steady climb. So, he then began a clinical study drug Tecentriq (atezolizumab, MPDL3280A), which has been shown to be effective in certain other cancers. In my husband's case, after 4 cycles of atezolizumab, his M-spike has continued its slow but steady climb, still increasing one-tenth of a g/dL, usually every other month. It was 1.10 g/dL at his last lab draw.

My husband agreed to take a 5th cycle of Tecentriq later this month, but if his M-spike goes up again, he's strongly leaning toward coming off the study. The reason: a femur bone lesion (that never caused him any pain before) recently became so fragile from the worsening myeloma in it that he had to undergo surgery last week to prevent imminent fracture. The procedure was an intramedullary nail fixation and seems successful so far. His orthopedic-oncology surgeon said he will need to undergo radiation to the femur, too, otherwise the myeloma will continue to destroy the bone in the lesion area and eventually loosen the new hardware.

So, five years after his diagnosis, he still has not had a transplant. We were very pleased with how well he did on KRD. If he had gone to transplant, who knows if he could have had 4 years before relapsing? Several people on this forum have posted they (or loved ones) relapsed relatively quickly after transplant. Others have experienced very long remissions. In my husband's case, his continuous treatments have been very inconvenient at times, and he's experienced a fair number of textbook complications and side effects from treatments.

Having said that, he continued to work the first four years after diagnosis, we traveled (after making some adjustments) and have lived a relatively "normal" life most of the time. Lots of ups and downs on the myeloma roller coaster, but that's just how it goes for many patients and their families.

All you can do is gather as much information as possible (including the Beacon as a valuable resource), make your decision, and then don't look back with regret! Good luck with your future treatment decisions.

Best wishes,
Chris M.

[kdaneedgar]

Re: Great response to Kyprolis, Revlimid & dex: what next?

by kdaneedgar on Wed Jul 13, 2016 9:00 am

I thank each of you for sharing your stories and opinions with me! This is truly a supportive site. I guess we are all in this together, and it shows through your compassion.

I own a small manufacturing business, and feel that an autologous stem cell transplant will force me to close it. I really don't want to do that at this stage of my life and of the disease. I also don't want to endure the problems that are associated with a stem cell transplant unless I really need to. Finally, I feel a duty to continue on the E1A11 study and provide data that will help others down the road. That said, I don't want to die earlier than need be!

My next month includes a visit with my oncology doctor Thursday (tomorrow), stem cell harvesting in late July, and meeting with a multiple myeloma specialist at the Mayo Clinic in early August. After that, I'll have to make the big decision about the stem cell transplant. Unfortunately, my insurance, through my wife who is an RN, will only pay for an stem cell transplant at their own hospital. So I have no way financially to shop around for that service.

I'll re-post as I learn more about my situation, just in case anyone is interested.

[Mark11]

Re: Great response to Kyprolis, Revlimid & dex: what next?

by Mark11 on Thu Jul 14, 2016 2:13 pm

Some well thought out posts in this thread.

Hi Kshhornb - You have to post more often. This is "spot on", in my opinion.

I had the same questions as you, why should I have the stem cell transplant if I was in remission? The way that it was presented to me was that they preferred to do the stem cell transplant when I was in CR, for a couple of reasons:

1. They typically have a better long term response, when you are in CR.
2. They told me that they cannot guarantee that they could get me back in remission, if I relapsed, to then do the stem cell transplant.

I would not attempt to give you advice as to whether you should continue chemo or not, or whether to do the transplant or not, it is most certainly a decision you have to make with your doctors, however what I have learned through this forum, and other research I have read, never underestimate this disease. It can sneak back up on you quickly, and trying to catch up can be a challenge. I chose to have the stem cell transplant (May 13th). I was determined to try and kill it off as much and as hard as possible.

Hi Rick - I think it would be more accurate to write something like "treatmen-free" after 5 years in this sentence.

In standard cancer care it takes 5 years without any disease before a doctor will say a patient is "cured".

Here is a part of a good article at the Fred Hutchinson Cancer Center website that discusses the issue of cure in cancer.

"That imprecision is reflected in the fact that an individual patient may not hear the word “cure” on their oncologist’s lips. But that doesn’t mean the word has no meaning to doctors and scientists, said Dr. Fred Appelbaum, transplantation researcher and deputy director and executive vice president of Fred Hutchinson Cancer Research Center. It’s just that it’s very difficult to apply it to a single person because it comes down to data — and time.

“When [scientists] say cure, we mean that the person is OFF OF THERAPY and that their chance of dying of that disease is no greater than someone in the general population. Now, you need large numbers of patients in a certain category to ever determine that,” Appelbaum said. “You get closer and closer to cure as you go further out from therapy, but to say you’re truly cured – it’s always something of a guess for any one individual.”"

That is basically what my doctor said to me at my first visit (celebration would more accurately describe it!) 5 years post allo.

Our specialist thinks that a cure may be in the offing for patients (like you) who have the best responses to KRD, but that the studies on this are still a few years out.

While I certainly agree with your specialist with regard to doing an auto while in an MRD-negative first CR, what makes him think the combo of a proteasome inhibitor / IMiD / steroid would be a cure for myeloma? Usually if a therapy is curative, there is some hint prior to long-term followup data on newly diagnosed patients that the therapy may be curative. Note that most specialists that use KRD keep their patients on maintenance. I think they would get their patients off of therapy since the first treatment-free interval is the best quality of life for a myeloma patient. I am hopeful that with the therapies that are currently available that can get patients to an MRD negative remission prior to doing an auto will result in a higher cure rate than the roughly 10% that we associate with an auto for myeloma currently.

I have a thread going here in the forum discussing the topic of if we are making progress toward a cure for myeloma. I would love to see more posts in it.

Mark