Cycle 3 Results

I finally got the last of the Cycle 3 test results today. The 24-hour urine analysis came back as "No monoclonal protein detected", which is the same result as last month. That's great news!

However, the serum protein electrophoresis revealed a Gamma M-Spike of 0.10 g/dl. That's also the same result as last cycle. I'm disappointed that it didn't go down, but at least it didn't go up. It is still well below the initial value of 0.29 g/dl before I started the clinical trial. This will be an important parameter to track as I continue this protocol. Overall, I'm responding quite well to this clinical trial.

As for my high Vitamin B12 issue, I now realize that I overreacted to that. You know how it goes when you tell someone "It hurts when I do this", and their response is, "Then don't do that anymore"? That sort of happened to me with the B12 thing. 

I said in my last post that I wasn't going to bother Dr. Richardson with this, but I did email the trial coordinator, Alice, about it. She asked if I was taking Vitamin B12 pills, and I acknowledged that I had been. She suggested that I stop taking them (duh!) and we can check the levels again in 3 months. 

The fact that she wasn't alarmed about my high B12 and didn't suggest doing anything about it shows that this whole issue is a big nothing burger! I need to chill out a little bit about some of these test results.  Oh, and I have some extra Vitamin B12 pills if anyone needs some.

I came across a video of Dr. Richardson discussing the results of this clinical trial after the ASH Symposium in December. It's somewhat technical, but if you are interested, here is the link:

Mezi Combo Therapy for Relapsed Myeloma

These results are pretty spectacular! Considering how well 90% of us patients are doing on the C3 arm of this trial, maybe there's another thing I should be more relaxed about, which is my amp(1q) cytogenetic glitch. Yes, it's a high risk, but I've always been high risk, and here I am 13 years later, still alive and kicking. So as long as I continue to respond well to this therapy, then it's all good!

Cycle 4 Day 1

I started my 4th cycle on the clinical trial yesterday at Dana Farber. Everything went well, as far as I could tell. I couldn't learn much from the early results of the blood tests, but most everything looked okay. so far.

I did get one very satisfying result. As you recall, my kappa light chain level had risen over the threshold for MM relapse, which got me into this clinical trial in the first place. I was relieved to see that it has not only continued to stay in the normal range but in fact has gone down. Here is the graph:

This result has given me some early hope that my remission might be back on track. I'm going to have to wait several more days before some of the other results come in. I'm most interested in the serum electrophoresis result, which won't be available until later next week. That's the one that went up last cycle. 

I'm hoping that that might have been due to the 3-week treatment delay caused by my Covid. When I spoke to the clinical trial team yesterday, they also thought that could be the reason. I'll just have to wait and see. 

One concern is that I have been becoming slightly anemic, even though I am taking iron pills daily. The trial team isn't too concerned, because this can be caused by the treatment itself. They did order some additional analysis of my blood draw, and one of the things that showed up is that my vitamin B12 level is very high! Here is a graph of previous results:

Now this isn't a parameter that is normally tracked.  The last time this was tested was in June 2022, and as you can see, it has been in the normal range for the last 12 years! So what is going on here? This could be something that has been going on for a while and may have nothing to do with my current treatment.

I did some online research to see what elevated B12 means for myeloma. The results I got were confusing. Elevated B12 is often associated with liver or kidney problems, diabetes (none of which I have), or certain forms of leukemia. Myeloma is usually associated with a low B12 count. Hmm.

Based on a bone marrow biopsy result back in 2016, Dr. Richardson thought I was at risk of developing Myelodysplastic Syndrome (MDS), which can develop into Acute Myeloid Leukemia (AML). However, nothing ever came of that at the time, although I am now taking folic acid and vitamin B1 as a preventative. 

Could it be that this has now raised its ugly head? Could it be that myeloma might be the least of my problems? Perish the thought! Obviously, I plan to discuss this during my meeting with the clinical trial team next month. I'm not going to bother Dr, Richardson with my frivolous concerns. I'm just bothering you with my frivolous concerns, which of course I expect to remain frivolous.

I'm glad I can share such an uplifting report. I'll have more news over the next week. Stay tuned.  

Silver Lining

I want to apologize for my last post. It was a bit negative, so I thought I would balance that with something a little more cheerful. 

I still haven't been able yet to get ahold of Dr. Richarson's ASH paper about my MeziDaradex clinical trial. His abstract talked about the Overall Response Rate (ORR). ORR is defined as the proportion of patients who have a partial or complete response to therapy. His presentation with updated results showed that the ORR has been over 80% on this trial. There was also a teaser in one of his YouTube videos that one of the cohorts in the trial achieved an ORR of 89%. 

There are three cohorts in the MeziDaradex clinical trial, B1, B2, and B3. When Dr. Richardson offered me the opportunity to participate, he suggested I enroll in Cohort B3, which I did.

After the ASH convention last month, the maker of Mezigdomide, Bristol Myers Squibb, issued a press release on Dec. 11. Their press release spilled the beans! It revealed that results at ASH showed that Mezigdomide combined with  Daratumumab and dexamethasone in previously treated patients achieved a response regardless of dose and schedule, with ORR observed in 82.6% of patients in Cohort B1, 62.1% of patients in Cohort B2, and 88.9% of patients in Cohort B3.

Yahoo, that's me! Color me B3! In Dr. Richardson I trust!

Now I don't want to get ahead of myself here. The amp(1q) is still a big issue. After finding out about that, I got a bit down, but you all know me as an optimistic person. I like to look on the bright side of things. Finding this press conference today brightened my mood considerably. 

I'm not "out of the woods" yet, but I'm ready for the fight. Bring it on!

I don't want to be overly pedantic (or do I?), but the etymological origin of the idiom "'out of the woods" can be found. Abigail Adams used it in a November 1800 letter found in the Papers of Benjamin Franklin. Just sayin!  

Fly in the Ointment

So far, I've been very happy with my progress on this clinical trial. However, as one might say, there is a "fly in the ointment".

Now that's a phrase I've used unthinkingly for most of my life, but what does it mean, really? On the surface of it, it doesn't seem to make much sense, right? Where did this phrase come from? The answer appears to be Biblical. According to Wikipedia, the likely source is Ecclesiastes 10:1: "Dead flies cause the ointment of the apothecary to send forth a stinking savour." Now I get it! I'm glad that's settled. But I digress.

I got my Cycle 2 blood serum and urine protein electrophoresis results today. The urine results still show no m-spike, which is great! However, the serum results got a little worse from the last cycle. The previous result showed a "faint M-spike that is not apparent on the electropherogram and, therefore, cannot be quantitated". The latest result, however, shows an M-spike of 0.1 g/dL. That's still lower than the 0.29 g/dL that I had back in October, but it's going in the wrong direction! 

It could be that the 20-day hiatus from Dana Farber that I was forced to take due to Covid might have slowed down or reversed the progress of the treatment. I don't know. I hope that's the case and that this is just a temporary glitch.

But that's not the only problem! I just recently noticed from my October 13 bone marrow biopsy results that in addition to my known t(4;14) and hypodiploidy cytogenetic abnormalities, I also now have chromosome 1q amplification, or amp(1q).  This abnormality must have been acquired at some point, as it wasn’t noted in my previous bone marrow biopsies. It's not unusual for genetic abnormalities of MM patients to evolve over time.

On researching this, I quickly discovered that amp(1q) is associated with severely adverse outcomes for MM. Oops! Now that's a bummer. Nothing that I have read about it yet is very encouraging. None of the MM drugs in clinical use today seem to have any beneficial effect on amp(1q).

However, these projections seem to fly in the face of the good results I have been getting so far in my clinical trial. I was a bit bewildered, so I decided to email Dr. Richardson to get his take on this.

As is his wont, Paul responded promptly. Here is his assessment: "I would suggest this genetic profile in your disease validates the treatment we have recommended as this does suggest higher risk disease, but I am very hopeful we are going in the right direction with your treatment, which is designed to deal with just such additional “risk”."

Hmmm. That's not exactly a ringing endorsement, but I guess that's the best I can hope for. Maybe my long string of extraordinary good luck with MM is about to be tested. I have to say that these recent revelations have been like a "bolt from the blue".

Now that's another phrase I've often used without exactly understanding its meaning. I thought it might refer to a bolt of lightning. However, as it turns out, an ordinary bow shoots an arrow, but a crossbow shoots a projectile called a bolt. Since a crossbow has a lot longer range than a bow, the bolt can seem to come out of nowhere. Okay, that settles that. But then again, I digress...

Cycle 3 Day 1

I was at Dana Farber today for the beginning of my 3rd cycle on the MeziDaradex clinical trial. It was a long day. I got there at 1:00 and didn't get out until after 6:30! They were short-staffed and everything was backed up. I brought in a 24-hour urine sample, and the analysis of that along with my blood serum protein electrophoresis results will give another data point on my progress to date. I expect those results over the next 3-4 days. I hope the time I lost because of Covid doesn't mess things up. Fingers crossed!

A weird thing happened when I was getting my subcutaneous Dara injection. The insertion line filled with blood, meaning Emily had hit a vein. She said that happens very rarely, but she had to do it over. I suggested that she find a different spot in my stomach! The next one worked much better.

Everyone is still anxiously waiting to get a copy of the paper Dr. Richardson gave at the recent ASH conference on this clinical trial. I will share it with you if and when I can get access to it. Alice Tattersall told me that his presentation was very well received by the Myeloma community. 

I also found out from the nurses that at a recent meeting between Dr. Richardson's team and the trial sponsor, Bristol-Myers Squibb (developer of Mezigdomide), I was a topic of conversation because of the outstanding response I had to my first cycle of the clinical trial! Wow! Needless to say, that made me feel pretty good. 

I know I may sound like a broken record, but I have been so fortunate over the years with my MM between Dana Farber, Dr. Richardson, and the amazing clinical trials I have been lucky enough to get enrolled in. I'm just so grateful! 

From now on, I only go into Dana Farber every other week for the next four 28-day cycles. After that, it will be once a month. Yay! My next appointment is scheduled for February 5 to get me back on a Monday schedule cycle. I was supposed to get a Zometa infusion today, but I rescheduled that for February 5. It's not related to the clinical trial, so it's no big deal.

I'll update this blog after I get the results from today's blood and urine samples. In the meantime, stay warm!

COVID Gap

Since my positive COVID test on December 14, I have been exiled from Dana Farber until January. Since then, I have been wearing the badge of dishonor and shame.

I wasn't really sick, mostly just tired and lethargic. After a few days, I felt better, but to my dismay, I still tested positive for COVID on December 21. I had no choice but to cancel my Christmas lunch that day with my good friends and business associates, Bahar and Dave. I hope to reschedule that soon. 

A family Christmas get-together was planned at my son, Jeff's, place, so I took another COVID test on Christmas morning. It was still positive! This was a dilemma. What to do? After checking with the family, I decided to go to our Christmas gathering wearing a mask and practicing social distancing. It turned out great, and we all had a good time. 

As the week wore on, I was feeling guilty and wondered whether I had infected anyone with COVID on Christmas. So I texted everyone on Friday. What I discovered was that almost everyone wasn't feeling well, but no one said that they had COVID! I thought there might be one of two reasons for this: either they didn't want to let me know because they knew I would feel terrible, or they didn't really care whether they had COVID or not. 

I'm beginning to think it might be the second reason. Nobody takes a test to find out whether they have the flu or a bad cold. They just deal with it until they get better. I think it's becoming the same with COVID. Who cares why you don't feel good. You know you'll feel better in a few days. Just deal with it. No matter what you have, you don't want to cough in anyone's face until you feel better. Who needs a test? Things have come a long way since the dark days of the COVID lockdown in 2020. 

Except at the Dana Farber Cancer Institute, that is. They still take this very, very, very seriously. As it turns out, I have an appointment supposedly scheduled for this coming Wednesday, January 3.  Ever since I was blacklisted, I've been wondering how I could get back in their good graces.

To clear my sullied name, the trial coordinator, Alice, emailed me with their requirements. I had to take two COVID tests this weekend 24 hours apart, and if they were both negative, I would be allowed to grace their halls with my presence on Wednesday. 

So I took a Covid test yesterday, which fortunately was negative. I took another one today which was still negative. Hooray! I emailed Alice back pictures of the two negative test results with time and date stamps. Hopefully, this will be enough for me to pass muster. Fingers crossed! Now I just hope that this three-week delay hasn't impeded my progress on the clinical trial. 

I said I would share any results I found about Dr. Richardson's paper at the ASH Conference. I found two recent YouTube videos where he discusses the clinical trial I'm on. Here are the links:

https://www.youtube.com/watch?v=SnRFxuh-aHk 

https://www.youtube.com/watch?v=34hCmqrE2JY 

In both of these clips, he talks about two separate arms of the study, the Daratumumab arm and the Elotuzumab arm. I'm not involved with the Elotuzumab part, so you can ignore the last part of these videos. 

If you get through the technical jargon, there are two major takeaways from these results. First, the overall response rate to the MeziDaradex trial is over 80%, up to 89% in some cohorts. This is remarkable! The other takeaway is that these responses are durable and long-lasting, with some patients still in remission over three years later. No wonder the staff at Dana Farber are so excited about this trial. Now I just hope that I will see the same benefits that most of the other patients have seen.

Bone Marrow Biopsy (Part 2)

This past Monday, I was scheduled for the dreaded bone marrow biopsy.  Since I had decided to take drugs, Holly drove me in in the morning for my first appointment. When it came time for the biopsy, I was given "conscious sedation", which consisted of an IV of Fentanyl (for pain) and Versed (for relaxation and memory block). 

Wow, what a difference! The procedure was a piece of cake. I'm going to go this route from now on with these biopsies. Holly picked me up afterward and we went back to their condo in Boston. I had no aftereffects.

On my last bone marrow biopsy on Oct 13, the results showed "monotypic kappa plasma cells present". Flow cytometry showed 1.8% of aberrant plasma cells in the bone marrow aspirate.  I was clearly diagnosed with a plasma cell neoplasm.

On Thursday, I got the results from the latest biopsy. This time, the result was clear: "No monotypic plasma cells detected"! They just disappeared! I'm flabbergasted. I can't believe how well this clinical trial is working right now. 

There's only one fly in the ointment. Sunday, I went to a funeral for an old college friend. One of the mourners became sick on Monday, and he tested positive for Covid. Since then almost all of us there have come down with it. I tested positive on Thursday. Being a good doobie, I called Dana Farber to let them know. To my shock and surprise, they told me I couldn't come back there for 20 days! this means I can't go back again until January. 

I'm really upset about this. After all the wonderful results I've achieved to date, I have to allow 3 weeks for things to possibly reverse. I realize that in severe cases, Covid can remain infectious for up to 20 days. So they are just going to let their cancer patients twist slowly in the breeze for 3 weeks? It doesn't seem fair.

I'll have to keep my fingers crossed that things will just pick up where they left off in January.

Looking Good

On Monday, I began my second 28-day cycle of the Mezi/Dara/Dex clinical trial at Dana Farber. I had several tests done to monitor my progress after the first cycle. They only update these tests once every cycle, so this is my first real snapshot of how I'm responding. Some of the results just came in today, so I thought now would be a good time to update my blog.

Multiple Myeloma (MM) is a cancer of the white blood cells. In MM, cancerous monoclonal plasma cells build up in the bone marrow. These crowd out the healthy plasma cells and make proteins that don't work right. This increase in monoclonal proteins is called an M-spike and indicates the presence of MM.

There are two ways to measure the M-spike. One is by blood serum electrophoresis, and the other is by 24-hour urine electrophoresis. Electrophoresis is a lab technique that allows proteins to be separated by size, and thus identify the monoclonal proteins. I had both of these tests done this week.

To consider MM to have relapsed, the blood serum M-spike must usually exceed 0.5 grams/deciliter (g/dL). My last two serum tests on Oct. 3 and Oct. 30 showed levels of 0.3 and 0.27 g/dL, respectively. While those are below the relapse threshold, they still represent a significant M-spike. The current test result was summarized as follows: "Immunofixation shows a faint M-spike that is not apparent on the electropherogram and, therefore, cannot be quantitated." Wow! It almost went away!

I also got electrophoresis results from my 24-hour urine sample. The last one I had on Oct 3 showed an M-spike of 115 mg/24hr. Again, while that is below the usual relapse criteria of 200 mg/24hr, it was still significant. Monday's urine electrophoresis test result was summarized as follows: "No monoclonal protein detected"! That is amazing! 

In addition to that, my Kappa light chain number, which had mushroomed and actually triggered my clinical relapse, is still back down in the normal range, where it had plummeted to after the first week. All other indicators are also good.

There is one other test I need to do that will measure the number of plasma cells in my bone marrow. I have a bone marrow biopsy scheduled for next Monday, Dec. 11. My last bone marrow biopsy on Oct. 3 showed a 5% level of plasma cells, below the relapse threshold of 10%, but still quite noticeable. 

I hate bone marrow biopsies! After my last one, I decided to opt for drugs this time. I'm going to have "conscious sedation" via IV to minimize the pain. Since I won't be able to drive, I'll be staying with Holly and Ryan in Boston on Sunday, and she has offered to take me in and back for this procedure, bless her heart!

Dr. Richardson is presenting his paper on this clinical trial this weekend at the American Society of Hematologists. I'm trying to find a way to get a video or a transcript of his presentation. If I can get it, I'll be glad to share it with anyone interested.

While this is still in the very early stages, I am thrilled that I seem to have responded so well over the first month. Dr. Richardson saved my life once. Maybe he can do it again.

Back in the Saddle Again!

I didn't update my blog last week when I got sent home for low white blood cell counts. I didn't want to scare anybody. 

I went back to DFCI yesterday hoping to resume my clinical trial treatment. Fortunately, my low white blood cell and neutrophil counts had completely recovered to their normal values. The Neupogen shot I got last Monday probably helped. I'm also feeling better from my cold, which probably also helped. So I'm back on the trial with only a one-week delay. Yes! 

While in the waiting room after my blood draw, I picked up the local weekly DFCI news magazine, "Inside the Institute". One of the articles was about a recent study that Dr. Richardson published in the New England Journal of Medicine about the effectiveness of my trial drug, Mezigdomide. The article published clinical trial results of combining Mezi with dexamethasone alone, which showed a 40-50% response rate, which is quite good. Of course, that trial preceded the one that I am now on including Daratumumab, which should provide even better results. 

I met with Alice, the trial coordinator. She told me that they are all excited about the paper on this trial that Dr. Richardson will be presenting at the American Society of Hematologists (ASH) convention in December. The results are starting to leak out, showing about an 80% response rate, and patients and oncologists from all over the world are now clamoring to get in on this trial. Unfortunately for them, the trial is closed to new patients as of now. Maybe they might open it up again...I don't know. 

Alice said that Dr. Richardson has been asked to present his paper at one of the major sessions of the conference. This is all very encouraging. I hope to be able to get a video, audio, or a transcript of his presentation. 

I hope everyone has a Happy Thanksgiving! I'll update this blog when I get more news.

Early Bird

In my last post, I said I'd let you know what the high-dose 40mg of dexamethasone would do to me. I then went to bed and slept like a baby. Oh well, who's to figure?

I worked out a schedule for taking the Mezigdomide pills. I kept them chilled in my bathroom overnight. When I got up to pee at my usual time around 5:30 or so, I took the pills and went back to bed. When I got up later, I was able to have normal coffee and breakfast. It worked out well. This week is my week off, so I don't have to worry about it.

Today marked Cycle 1 Day 8 of my clinical trial at Dana Farber. I had spent the weekend at the farm with Jeff, Christine, and Khoren closing it up for the season. I hitched a ride to upstate New York with them and planned to spend last night in Boston with Holly and Ryan. However, they weren't feeling well, so I drove my car home instead from Lowell.

My first appointment was at 6:50 a.m., so I set my Alexa alarm for 5:30. I awoke with a start and saw the clock said 5:45!  I didn't hear Alexa go off. I leaped out of bed, hurriedly dressed, grabbed my phone and computer, and jumped in the car. I was relieved to see that my GPS said I would get there in an hour.

About 40 minutes into the drive, I noticed something a little weird. It normally gets light here around 7:00 a.m., but with the clocks set to Standard Time, it should now be around 6:00. My car clock said it was 6:30, but it was still pitch black outside! 

Then dawn broke over Marblehead! It was 5:30, and none of the clocks in my apartment or car had been set back. My computer and phone had been on chargers, and my watch was in sleep mode, so I hadn't checked the time on them. Of course, Alexa knew it was only 4:30. Why didn't I figure that out? Duh!

Despite my bumbling early start, today was a much shorter one at Dana Farber. I didn't need to wait around for hours monitoring for side effects, so I got a blood draw, premeds, then the dex dosage, waited the prescribed hour to get the Dara injection, and left. The whole process only took about 3 hours, which should be the norm going forward.

I was curious about what my test results might look like one week into my clinical trial. I was hoping at the very least that the upward trends of my Kappa light chains and M-spike might have slowed a bit or even leveled off.

I haven't gotten my monoclonal M-spike electrophoresis results yet, but I did get my light chain report this afternoon on the Patient Gateway. I was blown away. My Kappa light chains have dropped all the way back into the normal range! Here is the graph of past results:

Kappa light chain history

This is so exciting!!! The entire last year's history of my Kappa light chain inexorably rising has been undone just one week into the trial. This was the only indicator that my MM had relapsed. Does this mean I may be back in remission already?

I don't want to get too carried away here. This is just one parameter to track. There may be other indicators that are not responding as well (M-spike?). Who knows? But I sure am happy about this! Am I on the right clinical trial or what? Yahoo!