Ibrutinib Continues to Demonstrate Viability in Treatment of CLL

Based on the results of the first in-human clinical trial of ibrutinib in chronic lymphocytic leukemia (CLL) – conducted in 2010 at Weill Cornell Medicine/NewYork-Presbyterian Hospital and other centers – researchers led in part by Dr. Richard Furman moved forward with the first phase II trial of the drug. According to a five-year follow-up study recently published in the American Society of Hematology’s Blood journal, ibrutinib continues to demonstrate excellent efficacy and tolerability as a single agent therapy for people with previously untreated and relapsed or refractory CLL.

CLL is characterized by uncontrolled growth of mature B-cells that accumulate in the blood, bone marrow, lymph nodes and spleen. As CLL cells fill these various organs, they interfere with normal cell functions. Ibrutinib is an oral treatment that inhibits Bruton’s tyrosine kinase (BTK), an enzyme involved in B-cell development that plays a critical role in CLL cell survival.

Prior to the Food and Drug Administration (FDA) approval of ibrutinib for CLL in 2014, chemoimmunotherapy (CIT), typically with fludarabine, cyclophosphamide and rituximab (FCR), was one of the only treatment options available for people with CLL. Chemoimmunotherapy often generates deep responses that last a median of five to six years, but it is associated with significant toxicities. When patients relapse after CIT, their disease becomes more resistant to subsequent treatments, and due to the accumulation of toxicities, many patients are unable to receive further CIT. Given the associated toxicities, the use of CIT is limited in older patients with comorbidities – the cohort that comprises the majority of CLL patients.

The phase II study in which Dr. Furman was involved tested ibrutinib as a single agent in over 100 patients – some of whom received no prior therapy, and others who relapsed following initial treatment. Patients received daily oral doses of ibrutinib until their disease progressed or until the presence of side-effects warranted discontinuation of therapy.

Almost 90 percent of all patient participants demonstrated a response to treatment at the five-year mark, and complete remission rates increased over time with ongoing treatment. Ninety-two percent of treatment-naive patients and 44 percent of relapsed/refractory patients remained free of disease progression five years out from the start of treatment.

Side-effects, including infections, diarrhea, bleeding and low-blood counts, were mild. They did not prevent patients from remaining on treatment long-term and often improved with continued dosing.

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Dr. Richard Furman, M.D.

“These data demonstrate the excellent long-term outcomes for CLL patients treated with ibrutinib, especially those who receive ibrutinib as their first therapy,” says Dr. Furman.

How Clinical Trials in Dogs with Lymphoma Can Lead to New Therapies for Humans

Studying animal models to enhance the overall understanding of cancer is a longstanding and valuable practice that, until recently, had been fairly uniform. The traditional model, the laboratory mouse, has occupied the oncologic arena since the 1980s, offering researchers a way to observe tumor growth and drug response in a natural environment, as opposed to in a petri dish. This approach, known as comparative medicine, more realistically represents how cancer behaves in humans and yields insight as to how scientists can effectively treat the disease.

Vet giving dog a check up

It wasn’t until late 2005 that a bigger, potentially better animal model entered the comparative medicine scene. Publication of the canine genome enabled comparison of dogs and humans at a molecular and genetic level, revealing biological similarities in each. In October 2017, the National Institutes of Health (NIH) recognized the untapped potential of the canine model in cancer research with a five-year $2.5 million grant awarded to Weill Cornell Medicine and Tufts University scientists to study new therapeutic strategies in dogs with lymphoma.

Dogs experience naturally occurring lymphoma that resembles the way that the disease manifests in humans. It is estimated that up to 80,000 dogs are diagnosed with lymphoma per year in the United States alone, with increased incidence in golden retrievers, whose lifetime risk for lymphoma is 1:8, as compared to a 1:50 risk in humans.

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Dr. Kristy Richards

“I want to cure cancer in people, and dogs provide a great opportunity for research that can help us move lymphoma therapies to the clinic for humans faster,” says the Lymphoma Program’s Kristy Richards, PhD, MD, who will lead the research as a co-principal investigator.

“We’re using the NIH grant to study immunotherapies and targeted treatment regimens in combinations that haven’t yet been tried in humans. The idea is to get to a therapy that can cure diffuse large B-cell lymphoma (DLBCL) in dogs. If it works well in dogs, we have better rationale to move the therapy forward in people.”

The immune system is the body’s in-house security guard that protects against infection and disease, but some forms of disease, like cancer, have evolved to evade the immune system’s defense mechanisms. Immunotherapies, which harness the power of a patient’s own immune system to fight cancer, rely upon an intact immune system, which lab mice grown in sterile cages and never challenged by sickness do not possess. Dogs, thanks to their propensity to eat, lick and roll around in whatever unsanitary substance they please, have thoroughly educated immune systems, a prime environment for testing immunotherapies.

But that is far from the only advantage of the canine model. “We can do things with the dog model that we can’t do with the mouse model, or even with the human model,” says Dr. Richards.

About two-thirds of human DLBCL patients enter remission following six cycles of standard chemotherapy regimen rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Dogs on lower, more frequent doses of the same treatment regimen almost always enter remission – but they also almost always relapse. If they were to receive the human dose intensity, they would suffer significant impairments to quality of life, such as decreases in physical activity and appetite, and vomiting and diarrhea.

Since standard chemotherapy cures nearly 70 percent of humans with DLBCL, current clinical trials of less toxic, non-chemotherapy based regimens are limited to the one-third of people who eventually relapse. Novel treatments used in these trials must be proven effective as single agents before being combined in what would ultimately require extensive (and therefore expensive) study.

The fact that dogs are not cured by standard therapies makes them the perfect candidates for testing of new, targeted therapies with fewer toxic side effects, permitting use of doses similar to those used in humans. Through use of these novel agents, dogs help science to leapfrog ahead of years’ worth of human trialing, while science helps dogs to live longer, happier lives.

Treating people’s pet dogs also encourages a humanistic approach. Much like in human oncology, scientists work to develop therapies that take more into consideration than just killing cancer cells, like quality of life, for example.

In fact, one of Dr. Richard’s favorite aspects about her research is that she gets to help the dogs that she’s studying.

“If we can manage to do something good for human medicine at the same time that we’re helping the model organism that’s helping us to study it, that’s a great thing,” she says.

Dr. Richards says that enlisting the help of the canine model to study lymphoma is a concept that is “arriving, but has not yet arrived.” Support from the NIH, as well as from organizations like Puppy Up and Paws 4 a Cure that raise funds to conduct clinical trials for dogs, plays a major role in validating the benefits of the canine lymphoma model, but further research is required to actually reap those benefits.

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What It’s Like to Transition to Work After Cancer Treatment

By Katie DeMasi

Four days before I was supposed to start my job as a registered nurse in New York City, I received a surprising Hodgkin lymphoma diagnosis. One of the first and most difficult decisions that I had to make was to hold off on working while I went through chemotherapy. I had just graduated from college three months prior, studied all summer to pass my nursing board exam, and had a job lined up – and I felt like I was throwing it all away. I felt like cancer had taken away so much from me.

In April 2017, when my doctor told me I was cancer-free, I immediately thought about how my life was about to begin again. (Well, actually, the first thing I thought about was when could I eat a hot dog, which ended up being right after we left the hospital that day.) But after even more thought and a discussion with my doctor, I decided again to put off work. I had just gone through the hardest eight months of my life, and I felt that I deserved to enjoy my summer before going back to work.

And I did! I spent a lot of time with friends and family, I enjoyed myself at the Jersey Shore, I indulged in foods that I couldn’t eat throughout chemo, and I got to travel to Italy. It was a summer I needed. After so much worrying and anxiety during treatment, I could finally just chill out.

As summer ended and my tan began to fade, I got ready to start my job as a nurse. I was both nervous and excited. My life was about to change. I was finally doing what I wanted to do.

Aside from the transition from total beach bum to full-time employee, I had to adjust in other ways, as well.

I’m in a “New Graduate” program at work, so when I first started and my co-workers asked where and when I graduated, I would reply that I graduated in May of 2016 – a whole year earlier. Some people weren’t fazed by my answer, while some asked me what I did for the year in between. That’s when I got tongue-tied and felt self-conscious. The long, complicated answer would be, “I had cancer.” But the short answer I chose was that I took a year off. I don’t know why. I think it all comes back to me not wanting people to feel bad for me. Honestly, I don’t think anyone would; it’s just so hard for me to tell strangers my story…which is weird considering I openly blogged about it for a whole year.

There were moments in the beginning of the job when I was so angry that I had missed a year of nursing because I had to go through treatment. I kept thinking about how if none of that had ever happened, I’d be one year into my career and wouldn’t have to make up excuses about my hair or why I took a year off. I let myself feel bad for myself. I let myself think about the “what ifs.” But that didn’t help anything.

I finally put myself in front of a mirror for a little pep talk. Yes, if I had started working last year, I’d be over the jitters that come with being a new nurse. I’d be more settled into my life, and maybe wouldn’t be as stressed out all the time. But I also wouldn’t be the person I am now.

Katie DeMasi Scrubs

Over the past year, I learned what it was like to be a patient. I learned how much nurses can impact your day. I learned how to be positive and strong. Even though I wish I didn’t have to know what it felt like to be in a hospital bed, I’m glad that I do. I can’t always relate to everything my patients are going through health-wise, but I can relate to them emotionally. When they’re frustrated, I don’t just hand out an empty, “I understand;” I really mean it. When they’re happy or get good news, I celebrate with them, because I know what that feels like.

It is a blessing and a curse that I had to go through what I did. I sometimes feel like cancer took away a year of my life, stripped me of what I was supposed to be and who I was supposed to become. It made starting my career harder because I was nervous that I would forget how to be a nurse. And sure, maybe I forgot some names of drugs or proper techniques, but I never forgot how to actually be a nurse. That comes from within, not from a textbook.

I remind myself every day that I am better because of what I went through. This is who I am supposed to be, and I’m still waiting for what’s to come. I know it’s going to be something great.

Katie DeMasi was diagnosed with Hodgkin lymphoma at age 22 and treated by Dr. Lisa Roth, head of the Weill Cornell Medicine and NewYork-Presbyterian Hospital Adolescent and Young Adult (AYA) Lymphoma Program. Katie chronicled her cancer experience on her blog, Tuesdays with Katie, and shares how her diagnosis has impacted her outlook on life as a guest writer for the Lymphoma Program blog.