Honestly, Not Such a Good Friday

This past Wednesday, I had a thoracentesis procedure in which a needle was inserted into the pleural space between my lungs and chest wall. This procedure was done to remove excess fluid, known as a pleural effusion, from the pleural space to help me breathe easier.

Michael Becker blogging from his laptop at NIH on April 15, 2017

During the procedure, Dr. Elliot Levy, an interventional radiologists at NIH trained in radiology and minimally invasive procedures, drained 1.5 liters from the pleural space. Almost immediately, I felt better and even while I was being wheeled back to my recovery room, I asked my wife Lorie to grab me a turkey sandwich from the cafeteria as I was quite hungry. It’s possible the large amount of fluid on my left side was putting some pressure on my stomach, which could help explain why I haven’t had much of an appetite lately.

By Thursday, however, the fluid was returning, prompting yet another thoracentesis procedure on Friday to remove 1.5 liters of fluid. The rapid nature of the fluid buildup means that I will most likely have an Aspira® drainage system surgically installed to conveniently let me drain the fluid buildup at home via a small catheter and drainage bags. That procedure is planned for Monday, so I have been staying at NIH since Wednesday and will be here over the weekend.

More importantly, however, a CT scan was also done on Friday morning with disappointing results. The cancer nodules grew since the last CT scan on March 7, 2017. This reflects true disease progression as opposed to “pseudo-progression” as discussed in a prior post. I have been taken off the clinical study with M7824.

My individual results do not reflect poorly on the future of M7824, but rather underscore that we still have a lot to learn about immunotherapy and cancer. While I may not have benefited from the drug, the resulting knowledge and clinical data may help guide future development and I am proud to play a part in that process.

At this point, if I received no further treatment and went on hospice, my likely survival would be about two months – although every patient is different. I have scheduled an appointment with my oncologist at MSKCC to discuss the pros and cons of chemotherapy at this stage, but the balance between quality of life and quantity of life is not trivial and I haven’t made a firm decision to go in this direction. Chemotherapy may only add a month or two of survival with a negative impact on my quality of life.

While I have been very open about my disease since originally being diagnosed in December 2015 and enjoy blogging, I will now be focusing much more time with my wife and daughters and finishing up my memoir, which I hope to have published. This will unfortunately mean less time for updating this blog and responding to emails.

Thank you to everyone who has offered their best wishes, thoughts, and prayers during my cancer journey. Having such an amazing support network of family, friends, and social media contacts has been a great source of strength and inspiration. Special thanks to my wife, Lorie, who has been by my side the entire time.

If you’ll indulge me, I would like to end this post with three requests:

  1. If you have a son or daughter, please talk to your doctor about the HPV vaccine, which protects against cancer of the cervix, vagina, and vulva in women; penis in men; and cancers of the anus and head/neck (including the base of the tongue and tonsils) in both men and women. HPV is a very common virus; nearly 80 million people are currently infected in the United States. About 14 million people, including teens, become infected with HPV each year, resulting in 30,700 cancers in men and women. HPV vaccination can prevent most of the cancers (about 28,000) from occurring.
  2. Help preserve federal funding levels by communicating with lawmakers about the critical importance of investing in medical research. There are far too many people suffering from cancer and this is not the time to cut the budget for the National Institutes of Health (NIH) by 18.3 percent, about $5.8 billion, as has been proposed. In an Op Ed by Harold Varmus appearing in the New York Times on March 22, 2017, he states that  only about 10 percent of the NIH’s budget supports the work of government scientists and that “over 80 percent of its resources are devoted to competitively reviewed biomedical research projects, training programs and science centers, affecting nearly every district in the country.” Harold Varmus, a professor at Weill Cornell Medicine and a co-recipient of the 1989 Nobel Prize in Physiology or Medicine, was the director of the National Institutes of Health from 1993 to 1999 and of the National Cancer Institute from 2010 to 2015.
  3. If you or someone you know is battling cancer or another disease, please talk to a physician about available clinical trial options. Clinical trials are a key research tool for advancing medical knowledge and patient care. Such trials are important to learn whether or not a new approach works well in people and is safe and which treatments or strategies work best for certain illnesses or groups of people.

Week Nine Just Fine

This is week #9 on clinical study, as I received my infusion of M7824 yesterday as planned. All of my pre-therapy vitals and bloodwork came back fine, which meant the treatment was a go. As with previous infusions, there were no issues during or after. Everything went just fine.

It was unfortunately a later night than expected, as Lorie and I just missed our 7:30pm train and had to catch one leaving the next hour. So, we ended up walking in the door at home around midnight. Could always be worse!

Following the discussion in my past few blog posts, I’ve been learning more about the concept of “pseudoprogression,” or the apparent growth of a tumor followed by sustained regression, which is common following treatment with checkpoint inhibitors. For example, I came across the video clip below by OncLiveTV that contains a discussion of “Pseudoprogression With Checkpoint Inhibitors in Non-Small Cell Lung Cancer,” where panelists explore the implications of this phenomenon for patients with NSCLC. While I do not have NSCLC, the overall concept of pseudoprogression with checkpoint inhibitors is relevant to my treatment and latest scan results – whereby the tumor growth exhibited could be from inflammation due to an ongoing positive immune response, or from an actual increase in the tumor that continues until the body’s immune system overpowers the cancer. It could also be a combination of the aforementioned. In any event, I think that pseudoprogression is an important concept for patients receiving some immunotherapies to better understand – especially when getting imaging results following treatment.

 

PS – anyone who knows me, knows that I’m a big Chicago Cubs baseball fan (having grown up in Chicago)…so I’d be remiss if I didn’t ask you to keep voting for retired catcher David Ross on this season’s ‘Dancing with the Stars’. In case you missed his debut performance, here’s a clip where he danced to Steve Goodman’s “Go Cubs Go” – while wearing Cubs gear.

Keeping the Faith with M7824

As evidenced by the extensive discussions following my biopsy from last Friday, a tumor is indeed a very complex structure. It comprises cancer cells and stromal cells, tumor infiltrating cells—both cells of the immune system and cells not by convention being of the immune system, as well as an extracellular matrix mainly of proteins and carbohydrates.

Following my recent CT scan, the hope from obtaining core biopsies from one of my lung nodules was to get a better sense of the cancer at a cellular level, which may help shed some light on whether or not treatment with M7824, a completely novel, first-in-class, bispecific fusion protein is working (see prior posts for more details).

In particular, the presence of immune system cells (T cells, or T lymphocytes) in tumor biopsies and their potential impact on prognosis have been studied for decades. T cells are a type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections. Broadly speaking they can be divided into two different types, “killer” CD8-positive T-cells and “helper” CD4-positive T-cells. CD8-positive T cells are critical mediators of adaptive immunity. They include cytotoxic T cells, which are important for killing cancerous or virally infected cells, and CD8-positive suppressor T cells, which restrain certain types of immune response.

Despite contributions by other immune cell subsets, CD8-positive T cells have emerged as the predominant effector in most cancer immunotherapy settings¹. Accordingly, many immunotherapeutic strategies (including checkpoint inhibitors, such as anti-CTLA4, PD1, and PD-L1 antibodies) are dedicated to stimulating, enhancing and maintaining responses by tumor-reactive CD8-positive T-cells.

Favorable outcomes have been demonstrated in patients where high numbers of CD8-positive cells were found at the tumor site in patients with head and neck cancer, breast, colorectal cancer and also for others solid cancers. In one study, head and neck cancer patients whose tumors were densely infiltrated by CD3-positive and CD8-positive T cells had a significantly longer overall survival (OS) and progression-free survival (PFS) compared with patients whose tumors were poorly infiltrated².

While there seems to be a consensus that CD8 infiltration is a good prognostic marker in most malignancies analyzed, however, the impact of CD8-positive T cells on clinical outcome may differ and is difficult to quantify. Not only is the type of T cell important, but also its location, and moreover the specific phenotype and function of those cells in the particular environment.

Nonetheless, based on the preliminary results from my recent tumor biopsy and other factors, it appears that there is sufficient evidence of immune system activation in the vicinity of the tumor to indicate that the experimental agent M7824 may indeed be performing as we hoped. Accordingly, I am in 100% agreement with my doctor’s recommendation to continue on the therapy and will receive my next infusion this coming Tuesday at NIH. After a few more cycles of therapy, another CT scan will be taken in the future with the hope of demonstrating that the recent tumor growth was from treatment effect “pseudo-progression” rather than true disease progression, which has been previously described with immune checkpoint inhibitors like M7824.

References:

¹ Targeting CD8+ T-cell tolerance for cancer immunotherapy. Stephanie R Jackson, Jinyun Yuan, and Ryan M Teague. Immunotherapy. 2014 Jul; 6(7): 833–852.

² Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. P Balermpas, Y Michel, J Wagenblast, O Seitz, C Weiss, F Rödel, C Rödel and E Fokas. British Journal of Cancer (2014) 110, 501–509. doi:10.1038/bjc.2013.640

 

 

 

Not as We Had Hoped

The results of today’s CT imaging procedure were not as we had hoped. Ideally, the dozen or so tumors in my lungs would have shown signs of shrinkage – indicating that the investigational drug was having a positive effect on the cancer. Instead, several of the tumors actually increased in size and a new spot even appeared in my spleen.

One of the hallmarks of immunotherapy, such as the checkpoint inhibitors, is the potential for a “delayed” response, which is not routinely seen with chemotherapy or other cytotoxic agents. Another biologic phenomenon unique to immunotherapy is “pseudoprogression,” or the initial radiologic appearance of an increase in tumor burden subsequently followed by tumor regression¹.

The CT imaging study cannot distinguish between cancer progression or inflammation as the reason for the increase in tumor size, so there is a chance that it’s due to inflammation and subsequent imaging tests in a month could demonstrate a reversal. However, it is also possible that the cancer isn’t responding to the investigational treatment.

To get more details, I’m undergoing a biopsy this Friday so that one of the lung tumors can be sampled. The preliminary information from that biopsy, which should be available next week, will help guide between cancer progression and inflammation. Decisions regarding how to proceed will depend on that outcome.

Needless to say, everyone’s hope was to have seen some sign of cancer regression on today’s CT scan and many teardrops were shed. The chances for a favorable outcome have diminished and must be acknowledged, but for now I’m persevering and will evaluate next steps following the biopsy results.

Sincere thanks to everyone who has offered their positive thoughts, prayers, and support. It is difficult to respond to each and every communication, but please know that I read “everything” and your time and effort is greatly appreciated. Special thanks to everyone at NIH for being so wonderful — even when faced with delivering bad news.

Now, more than ever, please keep all those positive vibes coming my way.

References:
¹ Amidst the excitement: A cautionary tale of immunotherapy, pseudoprogression and head and neck squamous cell carcinoma. Baxi SS, Dunn LA, Burtness BA.
Oral Oncol. 2016 Nov;62:147-148. doi: 10.1016/j.oraloncology.2016.10.007. Epub 2016 Oct 21.

Positive Mental Attitude (PMA)

Monday evening, my wife Lorie and I traveled to Bethesda, MD in advance of my third infusion with M7824, a completely novel, first-in-class, bispecific fusion protein (see prior posts for more details). However, this was my first time being infused as an outpatient in the day hospital, as prior infusions required a short stay in the hospital for blood work, observation, etc. As with the first two infusions, everything went smoothly yesterday, with no adverse reactions during or following treatment. We caught a 9pm train home and were in bed by 12:30am ET.

image

Caught sleeping on the Amtrak train ride home by Lorie on February 21, 2017. Long day!

As I posted on social media throughout the day while at the NIH, I was truly humbled by the outpour of support – especially hearing from people I haven’t seen in years or decades. Amid the sea of political rants and opinions via these channels, it was nice to be reminded that social media can be a positive experience. Throughout the emails, Tweets, and posts, a lot of people remarked that I sound and appear “surprisingly positive” and “happy.” And truth be told – they’re RIGHT.

Sure, I have advanced cancer – and I’m not Pollyanna about what the future may have in store for me as a result. But, I was very fortunate to participate in a clinical study with a quite promising, investigational immunotherapy that has, so far, had no negative impact on my day-to-day quality of life. That is a very stark contrast from what I experienced after going through chemoradiation. While the outcome is far from certain, participating in this clinical study has given me every reason to “hope” that the therapy will work. And it is that hope that gets me up in the morning…smiling…ready to face the new day.

Michael D. Becker receiving IV infusion with M7824 - a novel, first-in-class, bispecific fusion protein

Michael D. Becker receiving his third IV infusion with M7824 – a novel, first-in-class, bispecific fusion protein on February 21, 2017

If anything has changed recently, it has been for the better. I’m now focusing my existing time and energy where I want, and it has been liberating. Death is always knocking on our doors, but it isn’t until the sound becomes louder later in life that you discover new priorities and sense of urgency. In this regard, I’ve started writing my memoir covering a +20-year biotechnology career and have been working with an amazing editor. I always enjoyed writing blogs and newsletters, but Lorie strongly encouraged me to finally write a book and it has been quite rewarding thus far. My goal is to get it done by late summer or so (30,000 words so far…), and I will definitely let everyone know more details via this blog as the project advances. I also recently started a coffee table book project to showcase my photography work over the past few years, with approximately 200 images selected and a draft layout complete. To fund the latter, I plan on launching a KickStarter campaign to finish the design and secure a larger order to reduce the per unit cost. And most importantly, through my disease openness and this patient blog, I’m exploring numerous opportunities to help raise awareness for currently available vaccines that can protect boys and girls against human papillomavirus (HPV) subtypes that most commonly cause anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers.

So, yes…I’m a cancer survivor and I’m positive because I have “hope” and will continue until life shows me otherwise. Inspired? Good…that’s my goal!

Finally, special thanks to everyone for the thoughts, gifts and support. Hearing from people I haven’t seen in years has also been amazing. A truly humbling experience and greatly appreciated.

Round Two

It’s been two weeks since my last blog update, so I thought it was about time for a status report.

Earlier today I had my periodic clinic evaluation at the NIH following last Wednesday’s second infusion of M7824. Recall M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap (see prior posts for more details). At 22 days into this Phase 1 study, I’m still feeling good and haven’t experienced any side effects. Blood work, vitals, etc. all okay.

Michael and Lorie Becker; Valentine's Day 2017

Michael and Lorie Becker; Valentine’s Day 2017

It was a quick roundtrip between home and the NIH today, which allows me to be back home to spend dinner with my Valentine, wife, best friend and birthday girl (ps – all the same person). Before I headed out for my appointment in the morning, we had a few minutes to exchange cards and snap a quick photo (see right).

I’m now done with the inpatient infusions for the study, so my next dose will be administered one week from today and I can go home afterwards. Here’s hoping for more, completely uneventful updates in the coming weeks!

 

Feelin’ Alright

Standing on the train platform this morning on my way to NYC, the late British rocker Joe Cocker’s version of Feelin’ Alright was playing over the sound system. Not only a good song to start the daily commute, it seemed an appropriate theme for this blog post.

It was exactly one week ago today that I received my first infusion of an experimental cancer immunotherapy agent, called M7824, as part of a Phase 1 clinical trial at the National Institutes of Health (NIH). Recall from my prior post that M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap. While very early in the process, I’m happy to report that so far I’m feelin’ alright.

As someone who has received three cycles of chemotherapy and a total radiation dose of 70 Gray over seven weeks, I can say with conviction that, so far, being treated with an immunotherapy agent has been a proverbial walk in the park. In fact, if it weren’t for the fact that this clinical study is not placebo controlled, I would seriously question whether or not I was in the active arm of the study.

For example, in contrast to chemotherapy and radiation, I haven’t experienced any of the hallmarks of traditional cancer therapy, such as nausea or fatigue, with the experimental immunotherapy agent. Important to note, however, every drug has side effects and checkpoint inhibitors like M7824 are associated with their own unique spectrum of immune-related adverse events. These include dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. In some cases, these side effects can be managed with corticosteroids or diphenhydramine. Less frequently, clearly defined autoimmune systemic diseases, such as lupus, have been reported.

In fact, approximately 30-40% of patients treated with approved PD-1/PD-L1 checkpoint inhibitors (nivolumab/pembrolizumab) will have dermatologic complications. For most patients, dermatologic toxicity is the earliest immune-related adverse event experienced, with onset an average of 3.6 weeks after treatment initiation¹. Accordingly, it may be too early for me to be experiencing any such side effects.

Of course, having a “safe” drug is important – but for me, the real hope is that M7824 is effective in treating my recurrent disease. In this regard, in an interview with EP Vantage earlier this month, Luciano Rossetti, Merck KGaA’s head of R&D, told EP Vantage that M7824 is “the most exciting clinical asset in our pipeline right now” adding that it has yielded “spectacular” early data. You can read the full interview by clicking here.

I remain hopeful and strongly believe that my generation could be among the last to experience toxic upfront treatments like chemotherapy and radiation thanks to the many advances being made with immunotherapy.

References:

¹ Source: http://www.uptodate.com/contents/toxicities-associated-with-checkpoint-inhibitor-immunotherapy