Victor Velculescu

Victor Velculescu, M.D., Ph.D.

Nearly 19,000 de-identified genomic records from cancer patients treated by an international group of hospitals, including the Johns Hopkins Kimmel Cancer Center, have been collected in a database coordinated by the American Association for Cancer Research (AACR) and are now available to scientists across the globe.

The data was gathered from the genomic sequencing of thousands of patients’ tumor samples, including 59 cancer types. The clinical-grade genomics data included in the database focuses on a targeted set of genes typically used to diagnose the cancers or provide additional information to help doctors prescribe treatments, an indication of the high quality of the data.

In addition to the openly-available genomics data, scientists can apply to AACR to receive more in-depth clinical information about patients’ tumors, such as survival data and treatment regimens.

“We want other scientists to use this information to pursue their own scientific studies about cancer,” says Victor Velculescu, M.D., Ph.D., co-director of the cancer biology program at the Johns Hopkins Kimmel Cancer Center and member of AACR’s steering committee on Project GENIE (Genomics, Evidence, Neoplasia, Information, Exchange).

Velculescu says scientists could use to the data to find subgroups of patients with particular mutations to determine their response to certain anti-cancer drugs. The vast amount of data in the GENIE project and large numbers of patients enables this type of needle-in-the-haystack research, he says.

Each institution contributing to the GENIE project will continue to add data, and the effort aims to add more hospitals to its network.

Johns Hopkins Kimmel Cancer Center collaborators on Project GENIE include Alexander Baras, M.D., Ph.D., Christopher Gocke, M.D., and Ben Park, M.D., Ph.D.

VN:F [1.9.17_1161]
Rating: 0.0/5 (0 votes cast)
No Comments

Immunotherapy has become one of the hottest areas of cancer research, and the number of cancers successfully treated by immunotherapy is growing. Nearing the end of 2016, there are now four FDA-approved immunotherapy drugs that target immune system checkpoints to treat six types of cancer.

We asked Drew Pardoll, M.D., Ph.D., director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, to review this year’s research findings that have made a significant impact on this field.

Pardoll’s picks for the top five research findings are:

  1. Virus-associated skin cancer responds to immunotherapy.
    Results of a study published in April and presented at the American Association for Cancer Research annual meeting gave oncologists the first hints that “a new category of cancer may be highly responsive to immunotherapy,” says Pardoll. The study, led by the Fred Hutchinson Cancer Research Center and Johns Hopkins’ Bloomberg~Kimmel Institute, showed that half of 25 patients with Merkel cell carcinoma, a rare, virus-linked skin cancer, had major tumor shrinkage and outperformed conventional chemotherapy. Pardoll says that worldwide, more than 20 percent of cancers are associated with viruses, and scientists are studying such cancers for their response to immunotherapy.
  2. Immunotherapy replaces chemo as first-line weapon against lung cancer.
    The FDA approved two immunotherapy drugs as a second course of treatment for patients with lung cancer who do not respond to chemotherapy. Then, a study published in November, led by researchers at the Johns Hopkins Bloomberg~Kimmel Institute and other scientists, showed that lung cancer patients taking the immunotherapy drug pembrolizumab as first-line therapy fared much better than those who took chemo. Pardoll says that the study was a “dramatic demonstration” that so-called PD-L1 proteins are a biomarker for response to the therapy. Results from this study led the FDA to approve pembrolizumab as the first treatment for patients with lung cancer whose tumors express PD-L1 proteins.
  3. Safety Trials of Immunotherapy for Early Lung Cancer Pass “Go.”
    At an international cancer meeting in October, researchers from the Johns Hopkins Bloomberg~Kimmel Institute presented early data in a small number of patients with lung cancer that giving the immunotherapy drug nivolumab before their surgery to remove the cancer is safe and feasible. At the time of surgery, 40 percent of patients had over 90 percent regression of their tumor associated with influx of killer T cells. “Immunotherapy could potentially work inside the early-stage tumor as a vaccine that activates T cells, which can circulate through the body and attack residual deposits of cancer, ultimately causing relapse after surgery,” says Pardoll.
  4. When Immunotherapy Doesn’t Work, Researchers Ask Why.
    Despite response rates of between 20 to 50 percent in certain groups of patients, scientists still don’t know why the majority of people with cancer don’t respond to immunotherapy drugs. Some of the first clues to immunotherapy resistance are beginning to unravel. This month, a team of researchers led by UCLA, including those at the Bloomberg~Kimmel Institute, published results in Cancer Discovery that point to mutations in genes called JAK1 and JAK2 in a small number of patients. The genes produce receptors that glom onto an immune system-signaling product called interferon gamma, which is made by T cells when they spot a cancer cell. When mutations disrupt the production of JAK1 or JAK2, the signaling system fails to rouse the immune system’s attack on cancer cells. Additional research is being done to see if more patients who are resistant to immunotherapy have these and other mutations that influence the immune system.
  5. Oncologists need more education on how to spot immunotherapy side effects early.
    No drug is immune from side effects, and immunotherapy is no different. Oncologists are sharing their knowledge of immunotherapy’s side effects and how to combat them at medical meetings and educational seminars. A recent story in The New York Times highlights some of the drugs’ known side effects, including rare cases of diabetes, inflammatory arthritis and even death. Kimmel Cancer Center oncologist Julie Brahmer, M.D. speaks at medical meetings about recognizing immunotherapy-related side effects. In a panel discussion during The Washington Post’s Chasing Cancer summit, Pardoll said that oncologists “need to go back to school” to learn about a different set of toxicities than what they are used to managing with chemotherapy. “We know that when clinicians spot and treat toxicities early, most of the effects can be mitigated before they get serious,” says Pardoll. He adds that oncologists also need to educate patients receiving immunotherapy about symptoms that should prompt an immediate call to the doctor.

Looking forward, Pardoll says that emerging basic science research and clinical trials are demonstrating how to block multiple immune checkpoints simultaneously. Immunologists also are studying ways to develop therapies that target the metabolism of the immune system, thereby strengthening tumor-killing activity. The final frontier, he says, may be in gaining more understanding about how the microbiome or microorganisms, such as bacteria, influence tumors. Overall, he says, 2016 has been a “good year” for immunotherapy.

Watch a video introduction to immunotherapy.

VN:F [1.9.17_1161]
Rating: 4.5/5 (2 votes cast)
1 Comment

A ceremony was held yesterday at the White House to sign the 21st Century Cures Act, which authorizes $4.8 billion in National Institutes of Health funding for a broad range of biomedical initiatives, including cancer and precision medicine. Immunotherapy patient Stefani Joho [watch a video of Stefani's story] and Dr. Elizabeth Jaffee, deputy director of the Johns Hopkins Kimmel Cancer Center, co-chair of the Blue Ribbon Panel of advisers for Vice President Joe Biden’s Cancer Moonshot Initiative and associate director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy, attended the signing ceremony. The “Cures” Act provides funding for the Moonshot initiative, which is now named for Joe Biden’s late son, Beau, who died of cancer. “This is a national effort with broad bipartisan support during a time when new technologies are revolutionizing medical science,” says Jaffee.

 

VN:F [1.9.17_1161]
Rating: 0.0/5 (0 votes cast)
No Comments

In a head-to-head comparison between the immunotherapy drug pembrolizumab and standard chemotherapy as a first-line therapy for advanced nonsmall cell lung cancer, patients taking pembrolizumab had a 50 percent greater drop in the risk of death or disease progression and a four-month greater increase in progression-free survival compared with those who took chemotherapy.

JulieBrahmer2

Julie Brahmer

A report on these findings of an international clinical trial of 305 patients with stage 4 nonsmall cell lung cancer appeared Oct. 9 in The New England Journal of Medicine and is noted in today's Washington Post. What made the trial significant and novel, say the researchers, is that it included only people whose tumor cells were abundantly studded with so-called PD-L1 proteins.

“This is a group of patients we think should get anti-PD-1 therapy first before chemotherapy,” says Julie Brahmer, M.D., director of the Thoracic Oncology Program at the Johns Hopkins Kimmel Cancer Center co-director of the Upper Aerodigestive Program of the Bloomberg~Kimmel Institute for Cancer Immunotherapy. Pembrolizumab and another immunotherapy drug, nivolumab, are approved by the Food and Drug Administration to treat patients with advanced nonsmall cell lung cancer, but only after their cancers have progressed after treatment with chemotherapy.

Pembrolizumab, which is sold under the trade name Keytruda, blocks a molecular “handshake” between immune system T cells and cancer cells carrying PD-L1 proteins on their surface. With no handshake, T cells target the cancer cells for destruction.

Brahmer, who led the trial with a group of international scientists, says that another study showed little difference in progression-free survival of patients with nonsmall cell lung cancer who took a different PD-1 inhibitor compared with chemotherapy. “That study included nonsmall lung cancer patients with any level of PD-L1 protein on their tumors, but this study included only those with high levels of PD-L1 proteins on their tumor cells, whose tumors are more likely to respond,” says Brahmer. Some 23 to 28 percent of patients with advanced nonsmall cell lung cancer have high levels of PD-L1 proteins on their tumor cells. Nonsmall cell lung cancer accounts for more than 80 percent of an estimated 220,000 lung cancers diagnosed annually in the U.S.

For the study, funded by Merck, which makes pembrolizumab, tumor biopsy samples from 1,729 patients from 142 hospitals worldwide were evaluated by the researchers to determine which of them had more than 50 percent of tumor cells marked with PD-L1 proteins. From that group, 305 patients were randomly chosen to receive 35 intravenous doses of pembrolizumab over more than two years versus the standard treatment of four to six cycles over six months of one of five types of chemotherapy.

Among the two groups, 154 patients who received pembrolizumab had a median progression-free survival rate of 10.3 months, compared with six months for 151 patients on chemotherapy. Median follow-up was 11.2 months. The researchers estimated that patients who took pembrolizumab were 50 percent less likely to die from their cancer or have disease progression over the duration of the trial, which began in 2014. “Extending the time we can keep these patients’ cancer under control is an important step in creating more long-term survival,” says Brahmer.

The trial was stopped early because researchers’ interim analysis revealed the pembrolizumab’s benefit on progression-free survival. As a result, 66 patients who had received chemotherapy were switched to pembrolizumab, and more than half of them were still taking the drug at the end of the trial.

During the study, 108 patients died. One of the patients died after taking pembrolizumab potentially associated with that treatment, and three deaths were potentially caused by chemotherapy. The most common side effects in patients taking pembrolizumab were diarrhea, fatigue and fever. In patients taking chemotherapy, common side effects were anemia, nausea and fatigue.

“This study shows that immunotherapy can benefit some patients early on in their treatment, and our hope is that when we determine the best combinations of immunotherapy and targeted anticancer drugs, these patients may never need chemotherapy,” says Brahmer.

In her practice, Brahmer says treatment options for patients whose cancer progresses after taking pembrolizumab include clinical trials using combinations of immunotherapy drugs as well as chemotherapy.

Pembrolizumab’s cost can reach more than $100,000 annually for each patient, and Brahmer says her goal is to determine which groups of patients are more likely to benefit from it by itself. Plans are underway, she says, to study more closely the drug’s effectiveness in lung cancer patients whose cancers have lower levels of PD-L1 proteins.

Funding and materials for the study described in this press release were provided by Merck. Dr. Brahmer is also a paid consultant to Merck. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies.

Researchers who contributed to the study include Martin Reck from the German Center for Lung Research; Delvys Rodriguez-Abreu from the Hospital Universitario Insular de Gran Canaria; Andrew Robinson from the Cancer Centre of Southeastern Ontario; Rina Hui from Westmead Hospital and the University of Sydney; Tibor Csoszi from the Jasz-Nagykun-Szolnok County Hospital; Andrea Fulop from Orszagos Koraanyi TBC es Pulmonologiai Intezet; Maya Gottfried from the Meir Medical Center; Nir Peled from the Davidoff Cancer Center; Ali Tafreshi from the Southern Medical Day Care Centre; Sinead Cuffe from the St. James’ Hospital and Cancer Trials Ireland; Mary O’Brien from the Royal Marsden Hospital; Suman Rao from MedStar Franklin Square Hospital; Katsuyuki Hotta from Okayama University Hospital; and Melanie Leiby, Gregory Lubiniecki, Yue Shentu and Reshma Rangwala from Merck.

VN:F [1.9.17_1161]
Rating: 4.5/5 (2 votes cast)
No Comments

The University of Chicago and Johns Hopkins' Bloomberg~Kimmel Institute for Cancer Immunotherapy  have published a pair of studies looking at biomarkers involved in the immune system's response to tumors in the Nov. 7 issue of the Proceedings of the National Academy of Sciences.

The University of Chicago studies are explained here.

Janis Taube

Janis Taube

For the Johns Hopkins research, scientists studied 3500 tumor samples among nine cancer types recorded in The Cancer Genome Atlas to analyze five biomarkers of immune activity within tumors. They include: whether the microenvironment within a tumor is inflamed, the number of mutations present in tumor cells, and expression levels of immune-system related proteins called PD-1, PD-L1, and PD-L2, which can be coordinately expressed in the environment surrounding a tumor to ward off an immune system attack.

"Scientists have been looking at these markers independently, but we wanted to know how

they relate to each other and which was most influential in patients' survival," says Janis Taube, M.D., associate professor of dermatology and pathology at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Taube and her team found that all five factors were important in predicting survival of patients with metastatic melanoma.  Four of the factors — PD-1, PD-L1, PD-L2 and inflammation — have very tight links, they say, and their research suggests that when expression levels of these factors are high, they are more important in predicting patients’ survival than the amount of mutations present in the tumor.  However, when these factors are low, mutational load plays an important role in predicting survival.

"This is an important step in understanding how to develop multifactorial-biomarkers for predicting patient outcomes," says Taube.

VN:F [1.9.17_1161]
Rating: 5.0/5 (1 vote cast)
No Comments

Endocrinologists, or hormone doctors, are on your lung cancer treatment team “if it's clinically appropriate for them to be a part of it,” says radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus.

Hales notes that “Endocrinologists often look at hormone levels, and we use their expertise in patients who have underlying endocrine problems. We ask endocrinologists to evaluate some patients right after their therapy, patients whom we feel may be at risk for endocrine problems due to their radiation, chemo, or surgery. In that way, we can help these patients avoid some long-term side effects or manage them better.”

VN:F [1.9.17_1161]
Rating: 0.0/5 (0 votes cast)
No Comments

“Every clinical trial is done in a way to try to get a very homogenous group of patients, so we can better draw conclusions about whether the innovation we’re testing is actually working,” says radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus.

“A patient can be evaluated for a clinical trial, and we would look carefully at the stage of their disease, at their overall health, and at other factors to determine whether they're appropriate candidates for a clinical trial,” Hales added. “Clinical trials are available for patients with all stages of disease, from early stage disease to very advanced disease, and for patients newly diagnosed, as well as for those with recurrent disease. Trials are not one-size-fits-all. They're custom made for patients at varying points on the continuum of lung cancer treatment.”

VN:F [1.9.17_1161]
Rating: 0.0/5 (0 votes cast)
No Comments

Many lung cancer patients are concerned about the side effects lung cancer radiation can cause, such as heart or kidney damage, or fertility problems, says radiation oncologist Russell K. Hales, M.D. of the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus.

“Any therapy can cause short-term or long-term problems, and side effects,” Hales notes. “When we look at the benefit of these therapies, though, they have to be taken in context of the risks. If your physician has recommended radiation as part of your lung cancer treatment, it is far more likely to be beneficial, than to be risky. New therapies that help us target our radiation treatment more precisely have helped lower the risks to nearby organs.”

VN:F [1.9.17_1161]
Rating: 0.0/5 (0 votes cast)
No Comments

This blog post was written by Kristina Baum, who has melanoma and is participating in a clinical trial on immunotherapy at the Johns Hopkins Kimmel Cancer Center. For more information on Kristina's story, watch her interview with Denise Grady on the New York Times' Facebook page or follow her on Twitter at @kristinabaum. For the post, we asked Kristina to discuss what led her to join an immunotherapy clinical trial. 

When I was first diagnosed with melanoma in September 2012, cancer research was light years behind what it is now. When I was diagnosed this second time in June 2016 with metastatic melanoma, my oncologist, Dr. Evan Lipson, mentioned a clinical trial as my first option. Admittedly, the words “clinical trial” scared me. As I weathered cancer the first time, I remember patients going on clinical trials simply when they had no other options to consider. Clinical trials seemed like a last resort, or a type of lab rat experience when there was no other hope. However, as I gathered myself in the midst of the diagnosis conversation, I knew that Dr. Lipson and the team at Johns Hopkins were ones I trusted. Therefore, I knew there must be a good reason for their suggestion – and there was.

Kristina Baum

Kristina Baum

By going with an immunotherapy clinical trial, I ended up having more treatment options than I had initially anticipated. We pursued a trial with Opdivo and an experimental drug known as a LAG-3 monoclonal antibody made by Bristol-Myers Squibb. There were a limited number of slots on the clinical trial provided to patients at Johns Hopkins and I received one of them, which was a miracle because that spot was not available the week before I was diagnosed. I eagerly learned about the trial, and quickly heard about the many successes patients were having with immunotherapies. Dr. Lipson, my family, and I were all very optimistic.

However, bumps in the road occurred.

As I went in for my third infusion, I experienced a side effect that occurs in less than one percent of patients known as auto-immune meningitis. Basically, I had a terrible headache and was completely oblivious to the seriousness of what was happening. I was admitted to the hospital and carefully watched by a team of doctors, including Dr. Lipson, and was later released on a strict regimen of steroids. The inflammation quieted, and I resumed normal life at work. Each week, I get lab work done to watch my numbers and to keep track of my progress. Then, on August 1, great news emerged. My very first CT scan since being diagnosed the second time revealed that the tumor in my left kidney shrank from 2cm to a smaller 7mm! No other metastasis were present either.

The immunotherapy clinical trial was working!

Pursuing the experience of an immunotherapy clinical trial no longer has the frightening stigma I feel that it once had. I would encourage any patient to pursue an immunotherapy clinical trial for a number of reasons with one being that a clinical trial might allow you to receive medications based on the most cutting edge, up-to-date, freshly researched cancer developments.

One person encouraged me to not Google my cancer, as any cancer patient already knows, but for a different reason. Developments are being made in cancer research, especially at places like Johns Hopkins, at such a rapid speed that some articles or information that’s more than a few months old might well be out-of-date. Research in cancer immunotherapy is not only developing and growing quickly, but the word about its successes is spreading like wildfire. And I noticed that this “wildfire effect” is usually from the patients’ stories themselves. In other words, I was seeing that there were people out there with stage four cancer, just like me, who were achieving "No Evidence of Disease" results rather quickly through immunotherapy clinical trials. I was so encouraged, so hopeful, so inspired, and so sure that I had made the right decision. I also thought that in some small way, I could be a part of a choice group of people that hopefully help other patients that were like me, too.

I imagined another young woman in her early 30’s receiving the news of a metastatic melanoma diagnosis. I imagined her, just as I had been, as scared, unsure of next steps, her family and career somehow unfathomably having to go on hold and the overwhelming thought of “how do you even tell your loved ones?” I imagined her flooded with emotions from the news of the word “it’s cancer” and the swirling survival statistics doing gymnastics in her mind. The truth is, with an immunotherapy clinical trial, there is hope. Your life doesn’t have to go on hold, but you do need to be careful and listen to your oncologist. And the support I received from not just loved ones but also the Hopkins family has made this road an easier one to walk down. It’s not a “cure” but it sure is evidence to me that we’re moving in the right direction.

--Kristina Baum

VN:F [1.9.17_1161]
Rating: 4.8/5 (6 votes cast)
No Comments

“The best way to prevent lung cancer now is to make sure you're not currently smoking,” says Russell K. Hales, M.D.

Hales, who is a radiation oncologist at the Johns Hopkins Kimmel Cancer Center on the Johns Hopkins Bayview campus, notes that smoking, even as late as when you’ve had a lung cancer diagnosis, can improve the outcome of your treatment, in part because you can better tolerate therapy.

Is there anything that you can do to reduce your risk more, now? Hales says, “Lung cancer screening may be appropriate, although the benefits of screening have only been established for lung cancer patients who smoked for 30 years or more. Screening is also more than just a CT scan. We have other tests that we look at, markers in the blood, or in a patient's sputum, that can help us better identify which patients are likely to be at risk for lung cancer. Call 410-955-LUNG to find out more about screening.

VN:F [1.9.17_1161]
Rating: 0.0/5 (0 votes cast)
No Comments