Patient Spotlight Marc Muskavitch Boston area, Massachusetts, USA
Marc Muskavitch is an ALK patient, Board member for ALK Positive, Inc., and one of the leading members of the ALK Positive Medical Committee. We interviewed him on his journey with ALK+ lung cancer so far, his work with the Medical Committee, and what most excites him about the future of ALK+ cancer treatments and collaborations to improve outcomes for ALK patients.
1)Tell us a little about yourself - your personal and professional background as well as your journey with ALK+ lung cancer so far.
Like so many of us, I was a nonsmoker in good physical condition when a persistent cough during spring 2020 (COVID times) led me to request a chest Xray. Just 30 minutes after the Xray, my doctor called to tell me I had advanced lung cancer! This diagnosis hit me and my family as I was nearing the end of a 40-year career as a geneticist and biochemist, as a university professor, and as a member of and consultant to pharma and biotech companies. After decades of learning and teaching about cancer, I was diagnosed with cancer. Diagnosed at age 67, my children were grown, and I was blessed to be married to Brenda, who quickly and graciously transformed from my loving wife into my loving wife and care partner. Brenda continues to be a wonderful companion and support through the emotional and medical dislocations that an advanced cancer diagnosis has imposed on our life together.
Because I had the good fortune to arrange my treatment through MGH in Boston, my thoracic oncologist knew, within days of my diagnosis, that I was ALK+, which I always tell family and friends is my “good bad luck.” After confirming I was Stage IV, I began with Alectinib (Alecensa) as my first line therapy. I feel very fortunate because I have experienced a stable partial response with Alectinib. The numerous tumors distributed throughout my lungs and thoracic lymph nodes when I was diagnosed have diminished in volume and seem to have remained stable so far.
2) What do you know now that you wish you knew back when you were first diagnosed? What would you advise a newly diagnosed patient and their loved ones?
Because of my professional background, I had the benefit of understanding, from my diagnosis onward, a great deal about the biological basis of my ALK+ lung cancer. The mechanisms and misbehaviors of cancer cells, the tricks they play to evade our immune systems, and the means we deploy in our attempts to destroy them are matters I’ve studied for years. My understanding of the biochemical “machinery” of cells and its genetic encoding means that I grasp a great deal, although not all, of what makes ALK+ cancer such a wily foe and potentially deadly disease.
What I did not know when I was first diagnosed was that the ALK Positive Facebook Group and the ALK Positive, Inc. organization (API) exist, and that they are tremendous resources for patients, care partners and physicians who live with and treat ALK+ cancer. Nor did I know that many ALK+ patients benefit from three, and soon possibly four, generations of targeted kinase inhibitors (TKIs) that often prove very effective in controlling our disease, at least for a number of years, for many of us. I began learning about these organizations over the first months after my diagnosis, but I wish I could have learned about them in depth as soon as I was diagnosed.
For those who are newly diagnosed, I would say “you have reasons for hope.” The existence of multiple generations of TKIs means that you have more treatment options than patients with many other types of cancer. The existence of the Facebook Group and API are evidence of a large community of ALK+ patients, care partners and physicians who are working together to support one another, deploy existing treatments, and enable the creation of new treatments even more effective in controlling, and some day curing, ALK+ cancer. I would say “the only certainty is change.” This disease will change your life and the lives of those who love you. But life is full of challenges, and there is a community to support you as you address the challenges of ALK+ cancer. I would say “prepare for the future.” As soon as my first wife (who passed away in 2009) and I had children, and once Brenda and I decided to share our lives, we worked through planning and documents to address our final days and the days that would follow our passing. Working through those decisions can be difficult, but we felt it was best to do those things for ourselves and our family while we were clear-eyed and able.
3) You are a Board member of ALK Positive, Inc. as well as one of the most prominent volunteer members of the ALK Positive Medical Committee, actively pushing ALK research forward and leading our Translational Investigation Group (TIG) among other things. Tell us about what you do within the Medical Committee and why this work is so promising for current and future ALK patients.
My roles within the Medical Committee are those of patient and “professional scientist,” although I am only one of many scientists on the Committee. Because I understand the machinery of cells, I can often comment on the molecular mechanisms by which a given therapy works. Because of my experience in pharma and biotech, I understand the interior workings of those companies, including the steps by which they develop new therapies for patients. The promising work of all the components of the Medical Committee is focused on one goal: finding cures for ALK+ cancer. Because ALK+ cancer strikes randomly, it touches patients and caregivers with experience in research, medicine, biotech, pharma, business, and finance. All of those professional areas, and more, are represented within the Medical Committee.
Within the Medical Committee, I enjoy serving on the Research Acceleration Committee (RAC), Clinical Trials Committee (CTC) and Grant Review Committee (GRC) and co-leading the Translational Investigations Group (TIG) with Ken Culver. The TIG is advancing an exciting project using RNA sequencing of oncogene-driven tumor samples to define the biochemical “parts lists” for ALK+ cancer cells, cancer-supportive cells within ALK+ tumors, and immune cells that can attack ALK+ cancer cells. Understanding the parts of those cells can help us identify approved drugs against those parts, and drugs against those parts that are in advanced clinical development. We can then decide whether to advocate that those parts-targeted drugs be tested alone against ALK+ cancer cells or in combination with TKIs, to learn whether such drugs or combination therapies are more effective for controlling and killing ALK+ cancer cells. The bottom line is that we hope to use these parts lists to find better drugs for ALK+ patients. We do this through research that is supported by financial contributions to API, and that is conceived of and driven by ALK+ patients and care partners, in collaboration with allied cancer researchers and contract research organizations.
Within the Committee, the GRC funds external research to generate new insights into the biochemical and cellular mechanisms that cause and control ALK+ cancer. The TIG directs internal research focused on obtaining those insights in an even more targeted manner. The RAC prioritizes these new insights into our disease and identifies new therapies against it. The CTC identifies clinical trials well-suited for ALK+ patients and lobbies for inclusion of ALK+ patients in relevant clinical trials. We can all feel hopeful and encouraged about our futures as ALK+ patients, because dedicated patients, care partners and clinicians with a wide variety of professional skills are focused, through the many activities of the Medical Committee, on finding cures for ALK+ cancer.
4) Based on your professional background and your work for the ALK Positive Medical Committee, what are you most excited about in terms of future treatment options and breakthroughs for ALK-positive cancer?
There are many prospects on the horizon and moving into clinical trials, for new therapies for ALK+ cancer. Therapies that will increase the ability of our immune systems to control and kill ALK+ cancer are the most exciting to me.
Vaccines and oncolytic viruses in development may stimulate the immune system to kill ALK+ cancer cells more effectively. Targeted pulsed electric field and ultrasound therapies moving into clinical trials may make treatment-killed cancer cells more visible to the immune system and provoke killing of ALK+ cancer cells at the sites of treatment and at other sites that can be reached by our stimulated immune system. Therapies that inhibit “immune checkpoint” proteins other than PDL1 and PD1, and that will reduce the abilities of those immune checkpoints to block the killing of tumor cells by our immune system, could also prove effective against ALK+ cancer. “Bispecific antibodies” that bring immune cells closer to ALK+ cancer cells and increase recognition and killing of those cancer cells by our immune system, also offer promise.
Beyond all those therapies, next-generation TKIs like Nuvalent’s NVL-655 and antibody-drug conjugates that deliver toxic chemicals to ALK+ cancer cells constitute additional promising therapeutic options now in clinical trials. Odd though it may be to say, there has never been a better time to be an ALK+ cancer patient.
5) ALK Positive, Inc. recently entered into a partnership with Break Through Cancer with the goal of eliminating minimal residual disease in eligible ALK patients. Tell us a little about this partnership, what it is about, what it means, and why it can prove so important for ALK cancer patients.
Break Through Cancer (BTC) is a consortium of outstanding researchers and research institutions dedicated to “radical collaboration” to discover cures for difficult-to-treat cancers. Lobbying by determined ALK+ patients led BTC to begin a pilot research program that, if successful, will lead to ALK+ lung cancer being the first type of lung cancer to be investigated under the BTC umbrella. In this way, ALK+ lung cancer will be added to BTC’s current targeted cancers: glioblastoma, ovarian cancer, pancreatic cancer and acute myelogenous leukemia. Clinicians and clinician scientists who are experts in researching, understanding and treating ALK+ cancer will be added to the BTC consortium, expanding its scope to include ALK+ lung cancer.
The partnership of API with BTC means that our investments in BTC research will benefit from a “Return on Investment (ROI) multiplier” effect in which the impacts of a given investment by API will be “multiplied” by the collaborative efforts of hundreds of cancer researchers within BTC-affiliated institutions. The emphasis of BTC efforts on elimination of minimal residual disease (MRD) constitutes a critical focus for efforts against ALK+ cancer because, for those of us who respond successfully to initial lines of ALK-targeted therapy, it is the remaining MRD that evades initially effective treatments, becomes the source of cancer progression, and can lead to insurmountable ALK+ cancer that takes us away from loved ones.
So this API-BTC partnership offers exciting prospects to help us better understand, treat and eventually eliminate MRD, ultimately creating cures for ALK+ cancer. Still, while this is an exciting prospect, even a consortium with the many strengths and the resources of BTC can effectively address only a subset of questions critical for adequate improvements in the treatment, control and eventual cure for ALK+ cancer.
This means that API will have to marshal additional financial and programmatic resources to address other facets of ALK+ cancer biology, enable additional improvements in ALK+ cancer treatment, and improve the quality of life for ALK+ cancer patients worldwide. There is still much important work for us to do – as individuals, and within and beyond our ALK+ community – to increase the likelihood that we will see cures for ALK+ cancer during our lifetimes.
Interview by: Christina Weber