Department of Pathology News

Teaming Up to Bring Life-Saving Immunotherapy to C

Monday, May 01, 2017

Teaming Up to Bring Life-Saving Immunotherapy to Cancer Patients



 



ZhuHalmos-microscope

Drs. Changcheng Zhu, left, and Balazs Halmos





 



When the world learned, in the summer of 2015, that Jimmy Carter had been diagnosed with metastatic cancer, the prognosis looked grim. The melanoma had spread to the then 91-year-old former president’s brain and liver. Just months later, Mr. Carter’s doctors pronounced him cancer-free. The secret to his miraculous rebound? Treatment with radiation and an immunotherapy drug called Keytruda.

Immunotherapy, a revolutionary approach to cancer treatment, uses a new class of drugs known as checkpoint inhibitors to harness the patient’s immune system to fight tumor cells. It’s an effective alternative to conventional chemotherapy, with fewer toxic side effects. But immunotherapy doesn’t work for everyone.

Manufactured by Merck, Keytruda (pembrolizumab) has been approved by the U.S. Food and Drug Administration (FDA) as a first- and second-line treatment for non-small cell lung cancer (NSCLC), the most aggressive form of lung cancer. Doctors have also used it to successfully treat several other cancers, including melanoma.

How do clinicians decide which patients are likely to benefit from Keytruda? They rely, in part, on a diagnostic tool called the PD-L1 test. Fortunately for Montefiore oncologists and their patients, a PD-L1 test--PD-L1 IHC 22C3 pharmDx, developed by DAKO and approved by the FDA—is now available in-house through the Pathology Department’s Immunohistochemical (IHC) Laboratory. This companion test for administering Keytruda is regarded as the gold standard for PD-L1 testing. Test results are delivered within 24 to 72 hours—a time frame that can make a critical difference for patients with advanced NSCLC.



 



A Fruitful Collaboration



 

























zhu-team  PD-L1 stain 


Dr. Zhu and members 





of the IHC Lab team. 


 


PD-L1 stain.



 


 



“Montefiore was the first and is now one of only three academic medical centers in the New York metropolitan area to offer the PD-L1 test,” notes Changcheng Zhu, MD, PhD, director of the IHC lab and an associate professor of clinical pathology at Einstein.

“We used to order the PD-L1 test through a commercial reference laboratory, but it took 10 days to get the results,” says Balazs Halmos, MD, MS, director of thoracic oncology at Montefiore and a professor of medicine and director of clinical genetics at Einstein. “The clock is ticking for these patients. Sending the test to an outside reference lab wastes tissue—and precious time. The more we can streamline the process, the better it will be for our patients.”

With this in mind, Dr. Halmos and his team reached out to Dr. Zhu’s lab in 2015 and asked if they could develop the process in-house. 

“We wanted to answer the call from our oncologists,” recalls Dr. Zhu, “but it was a challenge.” To validate the test, the lab needed positive cases with known PD-L1 status, as well as negative cases, and it took time to collect them from a commercial laboratory. After a 10-month implementation process, the PD-L1 test went live at Montefiore in July 2016.



 



Unleashing the Immune Response



 



“Keytruda is a humanized monoclonal antibody that increases the immune system’s ability to help detect and fight tumor cells,” Dr. Zhu explains.
The PD-L1 test detects the percentage of PD-L1—the target antigen for Keytruda—expressed in the patient’s tumor cells. Based on the test results, the pathologist reviews the stains and assigns the patient a Tumor Proportion Score (TPS). A TPS of greater than 50% PD-L1 expression is considered positive; however, a recent clinical trial showed that even patients with a score as low as 1% can benefit.
“If you think about it logically, tumor cells should be killed by the patient’s own immune system,” says Dr. Zhu. “But tumor cells are smart. When they grow, they go undetected and suppress the patient’s immune system to prevent the immune cells from attacking them.

“PD-L1, an immune checkpoint protein, regulates the immune response by keeping cytotoxic T cells from attacking healthy tissue as well as tumor cells. Keytruda unleashes the suppressed immune reaction against the tumor cells, and kills them.

“We don’t interpret test results as either positive or negative,” he adds, “we just report the percentage of cells expressing the target as a TPS. We give this information to the oncologist. The oncologist then uses his or her judgment to assess whether or not a particular patient is a good candidate for the drug.”



 



The Power of Immunotherapy: Case in Point



 



“Patients who show evidence of the protein do much better on immunotherapy,” says Dr. Halmos. “They maintain their functionality better and experience long-term benefits.” To illustrate this point, he recounts a remarkable story: “One of our patients, a contractor and family man in his mid-40s, presented with NSCLC. Our initial treatment approach, targeted chemotherapy with detailed sequencing, was unsuccessful. Then we ran the PD-L1 test. The results showed that the patient was in the highest category of PDL expression, making him an excellent candidate for Keytruda.

“By the time he started treatment his life expectancy was measured in days. He actually ‘died’  and was resuscitated, twice. We began prepping him for hospice care when, suddenly, he started to improve. He got better and better, and has continued ever since. He’s running his business again, and he’s still receiving immunotherapy.” Dr. Halmos shared the story with a global audience, as a guest contributor to the http://health.usnews.com/health-news/patient-advice/articles/2016-04-12/harnessing-the-bodys-immune-system-to-fight-cancer" target="_blank">U.S. News & World Report. 



 



Impact on Patient Care



 



Currently, the IHC lab performs 5 PD-L1 tests per week. That volume will be increasing, say Drs. Halmos and Zhu, because PD-L1 will soon be a reflex test—that is, instead of being requested at the discretion of an individual oncologist, it will be performed as a routine test whenever the lab receives a tissue sample with a lung cancer diagnosis.

“We don’t dismiss chemotherapy completely, but it’s better for the patient to receive something more effective and less toxic, whenever possible,” says Dr. Halmos.

“PD-L1 is not a consistent or reliable predictive biomarker to exclude patients from checkpoint inhibitor treatment,” he adds, “but it can be used to predict how well a particular patient will respond to treatment. It can also help identify patients who are candidates for more aggressive, combined treatment strategies.”
 



 



Pathology’s Critical Role



 



“As oncologists, we’re committed to providing our patients the best possible care,” says Dr. Halmos. “And we’re relying more and more on our colleagues in the Pathology lab as an integral part of our team.

“We’ve been lucky to work with Dr. Zhu and his staff. They’ve been incredibly responsive. They steward the tissue specimens, maintain reasonable timelines and avoid running unnecessary tests. They read the results in a way that we can trust the information. Their expert interpretation is critical.”

For some patients, immunotherapy can have a downside. As recently reported in the New York Times, certain individuals whose cancer has been arrested by checkpoint inhibitors go on to develop unexpected, severe or life-threatening reactions such as a new type of acute-onset diabetes. Still, says Dr. Halmos, he and his colleagues in the oncology field remain optimistic.

“We’re finding that patients treated with immunotherapy do much better than those receiving conventional chemotherapy,” he says. “We’re just at the dawn of this exciting new era in cancer treatment. Obviously, more research has to be done.”

“The ability to do the PD-L1 test in-house is a win-win for our clinical staff, and for our patients,” says Dr. Halmos. “Our collaboration with Dr. Zhu and his team has put Montefiore on the cutting edge of cancer treatment. I am super happy with that.”
 



Recent News 

Cross-Campus Collaborations 

Recent Grants

joan-bermanJoan W. Berman, PhD, professor of pathology and of microbiology & immunology, and the Irving D. Karpas MD Chair of Excellence in Medical Research at Einstein, has been awarded a $3.5 million R01 grant from the National Institute on Drug Abuse to study the opioid derivate Bupenorphine as a potential therapy for neurocognitive symptoms in HIV patients.

 

Thanks to antiretroviral drugs, fewer HIV-infected people experience frank dementia, but more than half of those treated with anti-retrovirals suffer from milder, lifelong HIV-associated neurocognitive disorders, or HAND. Joan W. Berman, PhD, has been awarded two NIH grants totaling $7.4 million to study the sequence of events that lead to HAND; examine how certain drugs of abuse increase the risk for HAND; and develop strategies for preventing the disorder.  

  

Dr. Berman and Susan Morgello, MD, of Mount Sinai Icahn School of Medicine, were awarded a five-year, $3.6 million grant from the National Institute of Mental Health to study a population of white cells known to be responsible for HAND. The researchers will follow the migration of these cells in HIV-positive patients and study the proteins that regulate the transit of white cells across the blood brain barrier. The research may lead to therapies that block HIV-infected white cells from entering the brain. (1R01MH112391-01A1)

 

  

Dr. Berman and Harris Goldstein, MD, have been awarded a five-year, $3.8 million grant from the National Institute on Drug Abuse to study the interactions among methamphetamines and other drugs of abuse, antiretroviral therapeutics and HIV infection. The researchers hypothesize that methamphetamines and some anti-retrovirals weaken the integrity of the blood brain barrier, making it easier for HIV-infected white blood cells to enter the brain. Their research will also use a mouse model of HIV. Dr. Goldstein is professor of pediatrics and of microbiology & immunology and director of the Einstein-Rockefeller-CUNY Center for AIDS Research. He holds the Charles Michael Chair in Autoimmune Diseases at Einstein. (1R01DA044584-01) 

 

chandan-guhaChandan Guha MBBS, PhD, has been awarded a five-year, $2.3 million NIH grant to develop measures to prevent radiation-induced vascular injury (RIVI). In collaboration with Janssen Pharmaceuticals, Inc., Dr. Guha and colleagues will test whether the drug Thrombopoietin Mimetic can protect against vascular injuries caused by radiation. Dr. Guha is director of the Einstein Institute for Onco-physics, professor and vice chair of radiation oncology, and a professor of pathology and of urology at Einstein and Montefiore. (1U01AI133608-01) 

 

DavidFooksmanDavid Fooksman, PhDhas received a $417,500 R56 grant from the National Heart, Lung and Blood Institute to investigate myeloid-cell regulation of plasma cell engraftment into bone marrow. Dr. Fooksman is an assistant professor of pathology and of microbiology & immunology at Albert Einstein College of Medicine. 

Research

Experimental pathology aims to define disease in terms of fundamental molecular and cellular processes. Research in our Department is focused on critical issues in multiple disease classes. Areas of focus include 

Research in each of these areas is highly interactive, and the Department strives for a collegial atmosphere in which collaborations can flourish. This effort is conducted through a variety of department-level activities, including regular meetings to discuss work in progress and a departmental retreat at which students, postdoctoral fellows, residents and faculty all have opportunity to present and discuss their research.

Research Funding Program

The Department of Pathology has established a research funding program to encourage residents and fellows to participate in clinical pilot research projects. Up to $2,000 will be awarded per research project, for projects of up to two years in duration.

Research Faculty

Amanda Beck, DVM 

Geoffrey Childs, PhD 

Joan W. Berman, PhD 

Mahalia Desruisseaux, MD, PhD 

Amy Fox, MD  

David Fooksman, PhD  

Rachel Hazan, PhD 

Lawrence Herbst, DVM, PhD 

Huan Huang, MD 

Sunhee C. Lee, MD  

Fernando Macian, MD, PhD 

Maja Oktay, MD, PhD 

Harry Ostrer, MD 

Thomas J. Ow, MD 

Michael B. Prystowsky, MD, PhD 

Moshe Sadofsky, MD, PhD 

Laura Santambrogio, MD, PhD 

Bridget Shafit-Zagardo, PhD 

Herbert Tanowitz, MD 

Louis Weiss, MD 

 
 

Awards, Honors & Appointments

Michael PrystowskyMichael B. Prystowsky, MD, PhD, FCAP, Professor and University Chair of Pathology at Montefiore Einstein, has received the College of American Pathologists (CAP) President’s Honor. The award, which recognizes “outstanding and dedicated service to Pathology and to the College of American Pathologists,” was presented by Richard C. Friedberg, MD, PhD, FCAP, outgoing CAP President, at the CAP annual meeting in October. Dr. Friedberg thanked Dr. Prystowsky -- a longtime CAP fellow, a governor of the College, and a past chair and current vice chair of its Council on Education -- for his “thoughtful assessments” and “calm and analytical discussion, counsel and debate.” He added, “Michael’s enthusiasm to educate is legendary, and he has been a tremendous asset to the educational mission of the CAP. Residents around the world have benefitted from his analytical mind.”  Photo: Dr. Michael Prystowsky, right, with Dr. Richard Friedberg, immediate past president, College of American Pathologists, at the 2017 CAP annual meeting. 
 

Mark SuhrlandMark J. Suhrland, MD, director of cytology at Montefore and a professor of pathology at Albert Einstein College of Medicine, has received the College of American Pathologists (CAP) Foundation’s 2017 Herbek Humanitarian Award. The award was presented to Dr. Suhrland by Karim Sirgi, MD, CAP Foundation President, at the 2017 CAP annual meeting held in National Harbor, MD, in October. The Herbek award is bestowed on a CAP Fellow who provides outstanding direct patient services to individuals in underserved communities through a See, Test & Treat program. The award includes a grant which Dr. Suhrland will use to fund the production of public health brochures aimed at educating parents about the importance of HPV vaccinations for pre-teens and teens. The brochures will be distributed to attendees at Montefiore’s See, Test & Treat event in spring 2018. Photo: Dr. Karim Sirgi, CAP Foundation president, left, presents Herbek Humanitarian Award to Dr. Mark Suhrland, at CAP17.  Read more. 

 laura Laura Santambrogio, MD, PhDprofessor of pathology, of microbiology & immunology, and of orthopaedic surgery at Einstein, has had a busy spring, summer and fall. In May, Dr. Santambrogio was an invited speaker at the American Association of Immunologists annual meeting in Washington, DC, where she also served as leader of the Immunology Teaching Interest Group and organized the Block Symposium on Antigen Processing and Presentation. In July, she was an invited speaker at a Symposium on Proteostasis and Aging, in San Francisco. In September, she served as co-organizer of the 9th International Conference on Annexins, held in Cold Spring Harbor, NY. In October, she was an invited speaker at Jefferson University, Philadelphia, PA; Instituto Galeazzi, Milan, Italy; and Instituto Gaslini, Genoa, Italy. 

 

 James_SzymansiRandin NelsonRandin Nelson, MD, and James Szymanski, MD, are recent recipients of the AABB-Fenwal Transfusion Medicine Fellows (TMF) Scholarship Award. Funded by Fresnius Kabi, the TMF Awards Program recognizes professionals with a Doctor of Medicine or Doctor of Osteopathic Medicine degree who are current fellows in a Transfusion Medicine program or training program that includes at least one continuous year in Transfusion Medicine training. Recipients receive a $1,500 honorarium. 

Drs. Nelson and Szymanski are both graduates of the Montefiore Einstein Pathology Residency Program. Dr. Nelson completed his residency in 2014 and went on to do a two-year fellowship in Transfusion Medicine at the National Institutes of Health (NIH) in Bethesda, MD. He recently joined Montefiore Einstein as director of the Stem Cell Processing Laboratory and assistant director of Transfusion Services. Dr. Szymanski completed his residency in 2016. He is presently a fellow in Transfusion Medicine at the NIH. 

 

 MayaMaja H. Oktay, PhD, MD, has been promoted to the rank of Professor of Pathology. Dr. Oktay is a co-author of a study recently published in Science Translational Medicine (To read more, see Recently Published Research). 

 

 

 

 Nicole PanarelliNicole C. Panarelli, MD, has been promoted to the rank of Associate Professor of Pathology.  

 


 

 

 

 LeanaSerannoLeana Serrano-Rahman, MPH, (MT) ASCP, (CQA) ASQ, Blood Bank Manager, Moses, Weiler and Wakefield Divisions, is the lead author of a study, “Blood Management: One Hospital System Experience,” which was selected for display at the annual meeting of the AABB, held in San Diego, CA, in October. The study showed how an interdisciplinary committee successfully collaborated to reduce blood-product expenditures at Montefiore by nearly $1M in 2016 (as compared to 2015) despite higher patient volumes and a more complicated patient mix. Ms. Serrano-Rahman’s co-authors are Mallika Gupta, MBA, MPH, senior business operations consultant, Performance Excellence department; Susan Solometo, former vice president, Clinical Services; Ronald P. Walsh, MD, associate director, Transfusion Services; and Joan M.Uehlinger, MD, director of Transfusion Services at Montefiore and professor of pathology and of medicine (hematology) at Einstein. Ms. Serrano-Rahman represented the group in a poster session at the AABB meeting. The abstract will be printed in Transfusionthe AABB journal.   

RECENTLY PUBLISHED RESEARCH

In recent months, research studies by Pathology Department faculty members and trainees have been published in prestigious, peer-reviewed scientific journals.   View a sampling of these articles here.  

 

TRAINEE SPOTLIGHT

 

Matias Jaureguiberry-BravoMatias Jaureguiberry-Bravo, PhD 5th Year:  

Exploring a Novel Approach to Preventing HIV-Associated Brain Disorders    

  

 

NEW FACES

Welcome! 

New Faculty 

 

   

Debora Nautcsh Deborah Nautsch, MD, , has joined the Department of Pathology, in the Division of Surgical Pathology at Montefiore Medical Center, Montefiore New Rochelle and Montefiore Mount Vernon. Dr. Nautsch comes to us from InCyte Diagnostics in Yakima, WA. She earned her medical degree at Albert Einstein College of Medicine in 2011, and completed a Pathology Fellowship in GI/Liver at Montefiore in 2016.

 

 

  

Jennifer Oliver Jennifer Oliver-Krasinski, MD, has joined Montefiore Einstein as an attending physician in pediatric pathology, division of surgical pathology.

 

 

  

Shwerta Gera Shweta Gera, MD has joined Montefiore Einstein as an attending physician in cytology. Dr. Gera completed a fellowship in cytology at Montefiore Einstein in June 2017.

 

 

  

Randin Nelson Randin Nelson, MD, a 2014 graduate of the Montefiore Einstein Pathology Department’s residency program, has joined Montefiore Einstein as director, Stem Cell Processing Laboratory, and assistant director, Transfusion Services. 

 

New Residents  

RidinRidin Balakrishnan, MD. Dr. Balakrishnan comes to the Montefiore Einstein from Weill Cornell Medical College in Qatar. 

 

 

Angela-BaldwinAngela Baldwin, MD, MPH. Dr. Baldwin earned her medical degree at Howard University College of Medicine and her MPH at University of California San Francisco.

 

 

Mohammad-BarouqaMohammad Barouqa, MD. Dr. Barouqa is a graduate of the University of Jordan Faculty of Medicine in Amman, Jordan.

 

 

George-LominadzeGeorge Lominadze, MD, MPH, PhD. Dr. Lominadze is a graduate of Tbilisi and Ilia State Medical University in Tbilisi, Georgia.

 

 

Lin-WangLin Wang, MD, PhD. Dr. Wang received his medical degree from Heibei Medical University in Shijiazhuange, Heibei, China, and his PhD from the University of California San Francisco.

 

2017 - 2018 Fellows     

 BeamonAgarwa
Beamon Agarwal, MD, PhD
Hematopathology
 
 Abul Azad
Abul Azad, PhD
Molecular Genetics, ABMGG
 
 Aegean Chan Burnett
Aegean Chan Burnett, MD
Dermatopathology
 
 Mohammad Eskandari
Mohammad Eskandari, MD
Molecular Genetics
 
 Sonali Lanjewar
Sonali Lanjewar, MD
Women’s Health
 
 Patricia Raciti
Patricia Raciti, MD 
Dermatopathology
 
 Gloria Ramos-Rivera
 Gloria Ramos-Rivera, MD
Cytopathology
 
 Saed Sadeghi
Saed Sadeghi, MD
Hematopathology
 
 Sheila Segura
Sheila Segura, MD
Cytopathology
 
 Wei Zhang
Wei Zhang, MD, PhD
GI/Liver
 

Welcome Back!  

  

 Bing HanBing Han, PhD, a post-doctoral fellow in Pathology, Division of Parasitology and Tropical Medicine, has joined the Weiss Laboratory. Dr. Han comes to Einstein from the State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China, where he earned his doctoral degree. He previously trained in the Weiss Laboratory as a visiting student. 

  

Congratulations! 

Newly Minted PhDs  

The following graduate students successfully defended their doctoral theses:

 Nicole AnayannisNicole Anayannis PhD   

Mentor: Michael B. Prystowsky, MD, PhD 

Thesis Topic: “HPV-16 E2 Disruption and E6 and E7 Expression in Relation to Clinical Outcome in Head and Neck Squamous Cell Carcinoma”

 

 Nicole AnayannisIgnacio Guerrero-Ros, PhD 

Mentor:  Fernando Macian-Juan, MD, PhD  

Thesis Topic: “Lipid Challenge Negatively Affects Macroautophagy and Results in Reduced CD4 + T Cell Function” 

 

 Mike VeenstraMike Veenstra, PhD  

Mentor: Joan W. Berman, PhD 

Thesis Topic: “Mechanisms of Viral Seeding and Inflammation of CNS: Potential Therapeutics and Biomarkers for NeuroAIDS”

 

 RamaYakubuRama R. Yakubu, PhD   

Mentor: Louis M. Weiss, MD, MPH 

Thesis Topic: “The Arginine Monomethylome of Toxoplasma gondii and an examination of the role of MAG-1”  

Dr. Yakubu, an MD/PhD candidate, is currently working toward his medical degree at Albert Einstein College of Medicine. 

 

Recent Programs and Events  

Welcome Breakfast for New Residents - July 5   

The five incoming residents received a warm welcome from the Pathology Department’s faculty, residents and staff. Click to view photo. 

  

Residents Farewell Dinner - June 8   

Outgoing residents Evan Himchak, MD; Etan Marks, DO; Lauren McLemore, DO; Gloria Ramos-Rivera, MD; and Elizabeth Stuart Richards, MD, were honored at a festive celebration held at the Westchester Country Club in Rye, NY. Michael Prystowsky, MD, PhD, Professor and University Chair of Pathology at Montefiore and Einstein, congratulated the residents, thanked them for their outstanding dedication and service, and wished them well.  

All five residents were accepted to prestigious fellowship programs: Dr. Himchak in hematopathology (ACGME) at City of Hope Comprehensive Cancer Center, Duarte, CA; Dr. Marks in hematopathology at NYU Langone Health; Dr. McLemore in surgical pathology at MD Anderson Cancer Center, Houston, TX ; Dr. Ramos-Rivera in cytology at Montefiore. Dr. Richards is currently completing a fellowship in gastrointestinal and hepatopathology, University of Washington, Seattle. She will begin a second fellowship in general surgical pathology at Stanford University.  

The Davidoff Society Student Award went to Drs. Evan Himchak, Etan Marks and Gloria Ramos-Rivera, for their outstanding service as chief residents. Dr. Amy S. Fox presented the Resident Research Award to Dr. Marks. 

Pathology Department Annual Retreat 2017 - May 30  

Highlights of this year’s Pathology Department Annual Retreat included a poster session featuring the work of 30 students, post-docs, residents and fellows; oral presentations by predoctoral fellows Alex K. Ray (Mentor: Dr. Bridget Shafit-Zagardo), Rama R. Yakubu (Mentor: Dr. Louis M. Weiss), Matias Jaureguiberry-Bravo (Mentor: Dr. Joan W. Berman) and Mike Veenstra (Mentor: Dr. Joan W. Berman). Keynote speaker Alex Y. Huang, MD, PhD, associate professor of pediatrics, pathology, BME and general medical sciences, Case Western Reserve University School of Medicine, gave an inspiring presentation on “Cdk5 and PD-L1: Modulators of Immune Responses.” Click to view photo gallery.     

See, Test & Treat 2017 - May 13   

Funded by the College of American Pathologists (CAP) Foundation, See, Test & Treat offers uninsured and underinsured women from the Bronx free cancer screenings, onsite test results and referrals to follow up care. The Pathology Department spearheads this annual program at Montefiore in collaboration with the Departments of Radiology and of Obstetrics & Gynecology and Women’s Health. Click to read more and view photos.  

 

 Medical Laboratory Professionals Week 2017 - April 23 - 29   

The Montefiore-Einstein community marked this year’s Medical Laboratory Professionals Week with a series of educational programs and social events. Themed All-Stars Laboratory Team: Teaming Up for Patient Care, activities were held on all campuses to honor the diverse and dedicated group of individuals from the Montefiore-Einstein Pathology Department who staff our medical laboratories. Click to view photo gallery. 

 

 
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