[JessicaWynn]

Empliciti, Revlimid, and dex trial for smoldering myeloma?

by JessicaWynn on Sun Sep 11, 2016 4:20 pm

I am a 42 year old female recently diagnosed with smoldering multiple myeloma. Until this year, I had zero health issues. This past winter I had a number of sinus infections and colds, so in March of 2016, my doc did blood work to review immunoglobulins, where we learned that my IgG was high (2530) and IgA (81) and IgM (25) were low.

She said it was likely because I had chronic infections, but wanted me to get further testing. I did nothing until July when I started having flank pain. At that time, I learned that I had a mono­clonal protein present (2.0 g/dl) and was referred to an oncologist / hematologist. She sus­pected multiple myeloma and did further tests in August, with the following results.

1. Bone marrow biopsy shows 10 - 15% plasma cells
2. Cytogenetics revealed additional copies of chromosomes 3 and 11. Two hundred nuclei were analyzed revealing trisomy 3 in 17 nuclei (8.5%). Four copies of an intact non-rearranged CCND1 gene observed in 18 nuclei (9%). No abnormalities involving chromo­some 1, chromo­some 13q deletion or p53 gene deletion were observed, or was an IGH or CCND1 gene rearrangement detected. Hyper­diploidy characterizes a subset of plasma cell myeloma cases that is associated with better overall survival.
3. Full bone study revealed no bone lesions or suspicious radiolucencies
4. No CRAB symptoms
5. IgG: 2,620; IgA: 67; IgM; 25
6. Beta-2 microglobulin: 1.05 mg/L
7. Protein total 8.6 g/dL; Albumin 4.67 g/dL
8. Hemoglobin: Jan. 2015: 13.5; Feb. 2016: 13.9; Aug. 2016: 12.3.

My first opinion doc confirmed the multiple myeloma diagnosis and staged it at smoldering based on these results. She said I was low risk for advancing and told me I would live a long life.

I decided to get a second opinion at the Karmanos Cancer Institute on September 1, where the diagnosiss was confirmed, but the doctor said I meet the criteria for participate in a clinical trial using Empliciti (elotuzumab), Revlimid, and dexamethasone in high-risk smoldering multiple myeloma patients.

We did blood work again which showed little change other than in the free light chains, where we saw the following change.

Free kappa - 6.03 mg/dl;
Free lambda - 0.74 mg/dl;
Free kappa-lambda ratio - 8.15

According to what I have read, this moves me from the low risk for advancing to the moderate risk.

The criteria for the clinical trial are below. I meet 1 and 4.

1. Bone marrow plasma cell percentage greater than or equal to 10%
2. M-protein greater than or equal to 30 g/L (3.0 g/dl)
3. Ratio of abnormal to normal bone marrow plasma cells greater than or equal to 95 percent
4. At least one immunoglobulin level lower than the normal range.

I an struggling with the decision on whether to enter the trial. I have neuropathy in my hands and feet, but otherwise feel pretty good. I have started on a supplement regimen.

Looking for advice. Thank you so much in advance!

[JPC]

Re: Empliciti, Revlimid, and dex trial for smoldering myelom

by JPC on Tue Sep 13, 2016 1:52 pm

Hello Jessica:

This is a really current topic, with not many forum participants, I think, having direct experience in the question you are asking. I cannot give you a specific recommendation. If we were in­terested in a clinical trial, I would do a ton of research and weigh all the factors, which I have not done, and I do not know all of your issues. I do think (and have mentioned in the past) that I have observed doctors speculate that it will probably turn out to be the case that smoldering and early stage multiple myeloma in general will be one of the better phases to deploy the monoclonal antibodies such as Empliciti (elotuzumab).

A couple of general comments on clinical trials.

First, this is unproven. There is no hard data yet to suggest this will work, that is the purpose of the trial. On the other hand, in most cases, Empliciti has proven to be very active so far (not on its own, but in combination with Revlimid), and it's expected that it will be active in this setting also.

Second, understand how long will be the treatment plan. I think I have read that the treatment plan for Empliciti in its approved setting (relapsed) is for one year. Then they might add a year of maintenance. At that point, would they stop treatment? I would understand that question. I would expect that the purpose of knocking down the M-spike now with treatment would be to get you back to a better "watch and wait" scenario, and, in the long run, a hopefully longer time off treatment.

Third, I would hope that the trial does not require you to limit future treatment options in any way. Of course, you could go off trial if you needed to. However, sometimes the doctors will try and persuade you to stay on the trial, and as a practical matter, this could create a conflict in your treatment approach. Also, understand the side effects of the drugs. You really don't need them today.

All that being said, I think recent studies using Revlimid maintenance in high risk smoldering multiple myeloma have shown that patients on treatment delay the start to active multiple myeloma by something like 4 years. There was a recent update of a study on this topic by Dr. Mateos of the Spanish group, for instance. So, for example, an average high risk smoldering multiple myeloma patient under "watch and wait" progressed to active after about 4 or 5 years, with the treatment arm getting to 8 or 9 years.

However, in your case, there is no way to know ahead of time whether or not you are going to turn out to be "average", better, or worse (as with any individual). So I think the point of the trial is to prove that Empliciti, Revlimid, and dexamethasone will do better than Revlimid and dexamethasone. So far, Empliciti has done better in all settings that it has been subjected to on clinical trial, and the expectation or the hope is that it would also do better in this setting.

Now, here is another general comment, that again, we cannot be sure would apply to you. But IF the patients on this trial gain a number of years until progression, say, instead of 4 years, 6 to 8 years, for example, then, at the time you would need it, the treatment options would hopefully be BETTER, based on better understanding of the recently approved drugs, and new drugs that are in the pipeline, now. That I think would be the major upside of entering this study, which of course, needs to be weighed against the downside.

One last thing worth mentioning, just based on my recent research. Empliciti and Darzalex (daratumumab) are both new, but the early data seems to be that Darzalex is getting better results than Empliciti. You may not have a Darzalex clinical trial as an option to you, but if you did, I would look at that as potentially being more attractive than the Empliciti clinical trial.

Good luck to you.

[JessicaWynn]

Re: Empliciti, Revlimid, and dex trial for smoldering myelom

by JessicaWynn on Wed Sep 14, 2016 10:47 am

Thank you for your response JCP. I really appreciate your perspective as someone that has become very knowledgeable about multiple myeloma from the patient perspective. It is obvious that you are very well read and give excellent advice demonstrating your ability to navigate this complicated disease.

I will be getting a third opinion at the University of Michigan later this month and then back to Karmanos to make the final decision on trial participation. At this point, I am leaning towards participation. I would prefer to participate in a trial with Darzalex, but there does not appear to be any trials recruiting for smoldering. I find it somewhat perplexing that, while I hear many of the experts talk about the likely future of care to be treating early, there are very few trials available for smoldering. I could roll the dice and see if that changes over the next year or two, but I don't want to regret losing my spot in this study if it is my best shot and delaying progression.

Thanks again for your response. It was very helpful to hear someone else walk through their decision-making process for trial participation.