The Sentinel

THE OFFICIAL BLOG OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC).

Showing posts with label Merkel Cell Carcinoma. Show all posts
Showing posts with label Merkel Cell Carcinoma. Show all posts

Tuesday, September 3, 2019

A Tribute to Stan Collender: The Budget Guy, Immunotherapy Pioneer (Patient #1), Colleague and Friend (1951-2019)

By Michael B. Atkins, MD


Stan Collender was a man of many remarkable talents. Among his many achievements, he was widely recognized as one of the foremost authorities on the federal budget earning himself the moniker, “The Budget Guy,” and in 2012 receiving both the prestigious Howard Award for lifetime achievement in federal budgeting from the American Society for Public Administration and the James L. Blum Award from the American Association for Budget and Program Analysis. Stan was also my longstanding patient- an immunotherapy pioneer and an advocate whose experience and efforts taught us much about the impact and limitations of immunotherapy. Stan died May 3, 2019. Below is his cancer story from my perspective.

Stan Collender
I first met Stan in 2012 when he presented to my oncology practice status post resection of a Merkel Cell Carcinoma (MCC) on the bridge of his nose. We reviewed his history and the pathology and recommended a wide local excision and a sentinel lymph node biopsy. On hearing this recommendation, he joked that he was a local television celebrity so needed to protect his looks. I assured him that the plastic surgeon was up to the challenge.

After the successful surgery, we followed Stan at regular intervals. About 1 year later we noted he had developed an enlarged neck lymph node. Upon hearing this news Stan became diaphoretic, pale and promptly fainted. While he was out cold lying on an exam table and then gradually regaining consciousness, I remember thinking, “this is not going to be easy.”  But I never anticipated the novel, groundbreaking twists and turns Stan’s case would take, nor the heroic role he would assume as a patient advocate, or that I would be writing this posthumous tribute to a man I came to admire and care deeply about as a courageous colleague and friend.

Despite Stan’s tremulous start, he was an absolute rock thereafter. He underwent lymph node dissection and post-operative radiation therapy without a hitch. He subsequently developed a solitary brain lesion, which was also resected and treated with adjuvant stereotactic radiation to the resection bed. Unfortunately he developed widespread systemic disease six months later. In weighing treatment options available at the time, I recommended he participate in a clinical trial involving a then experimental immunotherapy, pembrolizumab, that we’d had good experience with in patients with melanoma, but had yet to test in patients with MCC. He volunteered for the clinical trial without hesitation, despite it being conducted in Seattle. He was literally Patient # 1 - a pioneer- on this important Cancer Immunotherapy Network (CITN) trial led by Drs. Paul Nghiem and Shailender Bhatia. Every 3 weeks he flew from DC to Seattle to receive his experimental treatment.  The pembrolizumab worked well: after two years of treatment his disease there was no visible signs of residual disease on imaging studies- his disease was apparently gone.  Not only did this treatment help Stan, but based on the results of this groundbreaking clinical trial, pembrolizumab receive FDA approval and is now the standard of care for patients with treatment naïve advanced MCC, providing benefit to countless patients with this disease.

Stan embraced this treatment success and his new lease on life with his typical gusto. He wrote an OpEd in the New York Times where he described his clinical trial experience. Rejecting the concept of being a guinea pig, he wrote he felt more like Chuck Yeager breaking the sound barrier and going where no one else had gone before. He encouraged others to participate in clinical trials and became a leading spokesman and a tireless advocate for the immunotherapy, MCC and cancer clinical trials communities. Just like Chuck Yeager in aviation, in MCC and immunotherapy circles, he became a national hero.

With his cancer in remission, Stan and I moved beyond our traditional patient-physician relationship: we became collaborators and friends. When Stan joined the Georgetown faculty, teaching public relations and public policy classes, we officially became colleagues.  Over lunches we strategized on how we could best represent the value of immunotherapy relative to other cancer treatments, as well as how to encourage cancer clinical trials participation and more public private partnerships such as the CITN trial he’d participated in.

Stan was frequently in attendance when I gave educational briefings to Congressional staffers, and welcomed me singling him out as Patient #1 on the MCC CITN trial. We served together on SITC committees focusing on measuring the value of immunotherapy, where Stan’s personal experience and budget expertise were both unique and invaluable. When I received my endowed chair, I was honored to have Stan and his beloved wife Maura, join me at the dinner ceremony and celebration.

In 2017, Stan was invited to give the Keynote lecture at the annual American Association of Cancer Institute’s meeting in DC. He talked about his views of the upcoming federal budget and its potential impact on cancer research funding, but he also described his personal battle with cancer, his experience as a survivor, and thanked me publicly for having encouraged him to pursue the CITN trial. Sitting in the audience, I felt both like a proud teacher witnessing my prized pupil excel, and grateful to see him healthy and choosing to apply his experience, talent and renewed health to benefit others.

Over lunches, we talked about his potentially running for Congress in the Virginia 6th in 2018 and how wonderful it would be to have a vocal cancer survivor and immunotherapy and clinical research advocate in Congress. He ultimately withdrew this pursuit, but came to my house for a gathering of concerned voters in his ex-candidate’s capacity to discuss the race and promote the candidacy of Jennifer Wexton - who ultimately was elected to serve the district.

And so it went. Stan and I had developed a shared mission and fought together on several fronts for its success. I thought we’d be doing this together for the rest of our careers.

Then all hell broke loose. Stan was almost 2 years out from his last therapy, a time when we usually consider patients who have responded to immunotherapy to be cured. So it was a shock when he presented in December 2018 with hand weakness, headaches and difficulty swallowing and a head MRI which showed that his lateral ventricles were packed with tumor. I had never seen anything like this presentation before and had no idea that MCC could do this. His tumor had recurred exclusively in one of the few places where the immune system doesn’t reach.

The word spread like wildfire through the MCC and immunotherapy communities. It was devastating. The pioneer/ hero- MCC patient # 1 - had relapsed. I was once again thrust into action as his physician, proposing a variety of approaches all focused on trying to get his immune system re-activated and into his ventricles where the tumor was hiding. A lot of my proposed treatments were quite involved and associated with considerable risk, but Stan was always positive. He would respond to my carefully chosen words of encouragement such as,  “I hope this works” or “This could work” with an optimistic “It is going to work” and a courageous “Let’s do it!”  Although Maura was more attuned to the uncertainty in my recommendations, Stan’s optimism usually prevailed.

Ultimately, the tumor could not be controlled and we ran out of both treatment options and optimism. Maura and Stan decided to focus on comfort measures. Stan passed away peacefully at home on May 3rd, 2019.

At his memorial celebration a few weeks later, person after person spoke about how they knew Stan, each describing a unique contribution he had made during his remarkable careers in Government, public policy, public relations, as well as in intramural football and as a family man. Clearly Stan was a true “mensch” with his many interests, passions and strong commitment to both his family and the world around him. His impact on the MCC, immunotherapy and cancer clinical trials communities was profound and enduring. Even in death, Stan remains a teacher and an advocate: his cancer taught us about potential new obstacles to effective immune therapy and like Chuck Yeager, his legacy as “Patient Number 1” will undoubtedly inspire research efforts to overcome them. I will miss this remarkable man- rest in peace my friend.

Sunday, November 12, 2017

SITC 2017 Scientific Highlights - Nov. 11

The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights from the Saturday programs (Nov. 11, 2017) of the 32nd Annual Meeting in National Harbor, Md. (Scroll to the bottom of this blog post to view the Glossary).



Dendritic cell acquisition of MHC I controls CD8+ T cell priming

Brandon MacNabb, BS (University of Chicago) presented data supporting the concept of MHC I antigen presentation by Batf3-lineage DCs as a critical component of CD8+-mediated anti-tumor response. Researchers initially generated H2-KbAB (MHC I+) and Kb-/-(MHC I-) C1498.SIY acute myeloid leukemia cell lines and subsequently engrafted C57BL/6 mice to determine the contribution of tumor cell MHC I presentation in CD8+ T cell priming. Initial assessment revealed reduced tumor growth in C1498.SIY KbAB mice compared to C1498.SIY Kb-/- mice. CD8+ T cell proliferation was also increased in KbAB mice compared to Kb-/- mice (p < 0.05). The observed C1498.SIY KbAB-dependent CD8+ proliferation was abolished in Batf3-/- C57BL/6 mice (p < 0.01). IFN-Ï’ secretion was also decreased in Batf3-/- KbAB mice, suggesting that Batf3 initiates CD8+ priming. Transfer of autologous T cells from KbAB tumor-bearing mice offered complete protection from tumor growth in tumor-free mice. Conversely, autologous T cells from Kb-/- mice offered no such protection. Interestingly, DCs isolated from the TME and the tumor-draining lymph node in tumor-positive mice had increased KbAB MHC I expression (p < 0.001), suggesting DC acquisition of tumor-derived MHC I. Ex vivo experiments confirmed that migratory KbAB DCs are capable of CD8+ priming. These data reveal the importance of Batf3-lineage DCs and tumor-derived MHC I presentation in CD8+ T cell activation of anti-tumor response, providing insight into potential development of DC-oriented therapies.