As The Leukemia & Lymphoma Society (LLS) embarks on a quest to disrupt the status quo in treatment and care for children with cancer, I was interested to learn the latest in children’s oncology while here at The 2019 ASCO (American Society of Clinical Oncology) annual meeting. More than 40,000 cancer scientists, clinicians, advocates, biopharmaceutical company reps and others from around the world are in Chicago to gauge where we are in cancer research and where we still need to go.
LLS seeks to bring about a wholesale shift in the standard of care for pediatric patients. Too many children are still dying from acute leukemia, and for those who do survive, the toxic chemotherapies leave many with lifelong health challenges. We are determined to advance safer more effective treatments that precisely target cancer without harming the rest of the child’s body. Through The LLS Children’s Initiative we are doubling our investment pediatric cancer research, and expanding services like back to school programs for children, education programs for pediatric physicians and financial assistance for families of children with cancer. And we are convening an unprecedented collaboration with a goal of launching a global precision medicine clinical trial for children with acute leukemia next year. We’re calling the trial LLS PedAL (for pediatric acute leukemia).
With all this in mind, I set out this weekend to learn what I could about the state of pediatric cancer treatment.
A Friday session presented results of several clinical trials investigating new treatments for children with cancers, including sarcoma, neuroblastoma and acute myeloid leukemia (AML).
While we have seen progress in new therapies for adults with AML – seven in all approved in 2017 and 2018 - progress for children with AML has lagged. Children are not mini-adults and they need fundamentally different strategies.
Two of the studies presented Friday offered signs of hope.
Todd Michael Cooper, M.D., of Seattle Children’s Hospital described a study testing the drug CPX-351 (Vyxeos®) in children aged 1-21 with relapsed AML. LLS supported the early development of this drug through our Therapy Acceleration Program (TAP). Vyxeos is a reformulation of two standard chemotherapy drugs encased in a tiny liquid bubble, optimizing the ratio and delivery of the medicine. It was approved for adults with secondary AML in 2017, marking the first new therapy for AML in decades.
Cooper said the study’s goal is to get the children into remission long enough to bridge them to a potentially curative stem cell transplant. The children were treated with a regimen of CPX-351 followed by a combination of standard chemotherapies. Of the 38 patients enrolled, 68 percent achieved a complete remission, and 83 percent of t hose patients were able to have a successful stem cell transplant. Cooper said the results warrant further study in a Phase 3 trial. Cooper is also part of a task force working with our Chief Medical Officer Gwen Nichols, M.D., to develop the LLS PedAL trial.
Jeffrey E. Rubnitz, M.D., of St. Jude Children’s Hospital, followed with a presentation on another breakthrough therapy recently approved for adult AML patients. LLS long-supported the early research of this therapy, venetoclax (Venclexta ®), first leading to its approval in chronic lymphocytic leukemia, and last year for AML.
Rubnitz showed in an early study that venetoclax was safe and well tolerated by children, and 75% of the children achieved a complete remission. He noted two children in particular, a seven-year-old and 11-year-old boys, respectively, both of whom were highly resistant to treatment but achieved remission with no evidence of disease with this regimen and went on to have stem cell transplants.
Michael Zwaan, M.D., of Erasmus MC-Sophia Children’s Hospital and Princess Maxima Center of Pediatric Oncolgy Utrecht, in Rotterdam, The Netherlands, moderated the session. In conclusion he posed the question: Can we move beyond cytarabine? (the standard chemotherapy used for decades to treat children with leukemia. His answer “Yes we can!”
Dr. Zwaan said his institution and others in Europe are eager to participate in LLS’s PedAL because well-designed trials in relapsed AML are sorely needed.
CAR-T for Glioblastoma in Children?
The revolutionary chimeric antigen receptor (CAR) T-cell therapy is a procedure first pioneered in the blood cancers that trains a patient’s own T cells to find and kill cancer cells. It appears to be curing hundreds of leukemia and lymphoma patients who had relapsed multiple times and had run out of options. Since it made history gaining approval in 2017 for children and young adults with acute lymphoblastic leukemia, and adults with relapsed lymphoma, scientists have been trying to get this therapy work for patients with other cancers like myeloma and AML, as well as for solid tumors. To date, they are still confounded by the challenges of making it work for these other patients.
Staying with the theme of pediatric cancer treatment, I attended a session on Saturday afternoon focused on clinical trials testing CAR-T in children with glioblastoma, a tumor of the brain. Nabil Ahmed, M.D., of Baylor College of Medicine, discussed the results of several trials. To date, despite glimmers of hope, success in treating glioblastoma patients with CAR-T has been fleeting. The obstacles include:
Too many different types of cancer cells within a single tumor, making it hard to find the right combination of treatments. Multi-CAR-Ts (“carpools) may need to be developed, Ahmed said.
CAR-T cells have been described as a living drug because they continue to multiply and attach the cancer once they are infused back into the patient, but in clinical trials for solid cancers, the CAR-T cells do not persist for more than several days, weeks or months.
The antigens - the specific molecules that the CAR T-cells are designed to attack - are disappearing for some reason.
While the progress has been halting, Ahmed said there is reason for optimism as researchers are determined to devise strategies and will ultimately succeed in overcoming these challenges.
They came from California, Colorado and Arizona, North Dakota, New Hampshire, Texas, Louisiana and Minnesota, each with their own story to tell. In all, 36 volunteers representing 25 states came to Washington D.C. this week to learn how to effectively use their stories to advocate for policies to protect blood cancer patients’ access to treatment and care. For three days these patients, survivors and caregivers took part in a training session with the dedicated policy and advocacy staff of The Leukemia & Lymphoma Society, preparing to be effective advocacy leaders, honing their story-telling skills and sharpening their understanding of two issues they would present to their legislators and staff members on Capitol Hill.
Each had a deeply personal reason for being there:
Callan Kriedel, of Tennessee, who like any 22-year-old college student felt invincible, purchased a short-term limited duration insurance weeks before graduation to bridge the gap until she began a new job, only to learn days later she had lymphoma; her plan fought her on covering what they deemed a pre-existing condition.
Jeff Saper, of Westchester County, NY, lost his seventh-grade son, and Abby and Aaron Breyfogle, of Minnesota, lost one of their baby twin girls, both children succumbing to the lethal acute myeloid leukemia.
Laurie Adami, a mom who battled lymphoma with an endless and, for her, largely ineffective arsenal of different therapies over 12 years, starting when her son was seven; Only when she was nearly at death’s door did she achieve a miraculous remission from an experimental, revolutionary immunotherapy - CAR T-cell therapy. This week Laurie celebrated her son Gus’s completion of his freshman year of college.
Michelle Lawrence, of New Hampshire, who at 31 years old, received a rare lymphoma diagnosis and a prognosis from her doctor that gave her two years to live; that was 10 years ago.
Lois Rosenblum, of California, who at 81-year-old has been living with lymphoma for 17 years.
And on and on…
And so, after a night of practicing they headed for the Hill first thing in the morning with two asks:
The first ask was for Members of Congress to support legislation guaranteeing parity in the cost-sharing between patients who get their drugs in pill form at a pharmacy and those who receive treatment via IV infusion in a hospital or clinic. Many insurers treat these patients differently –requiring patients taking drugs in pill form to pay a percentage of the very high cost of the therapy, while patients receiving an IV drug often only requiring a set co-pay. The bipartisan Cancer Drug Parity Act (HR 1730/S 741) would put a stop to this problem to ensure access to cancer drugs, regardless of how they are administered.
The advocates also asked their legislators to push back against the Administration’s promotion of short-term insurance plans. These plans were originally designed as a stop-gap for consumers between jobs or due to other circumstances that cause them to lose insurance, provide woefully inadequate coverage; they are frequently referred to as ‘junk plans,’ since they don’t typically cover basic benefits like prescription drugs. The House was preparing to vote on a bill, HR 1010, to rein in these plans the very next day, and advocates urged the Senate to follow suit by supporting S 466.
Our advocacy reached another level on Wednesday afternoon, when one of our volunteers, David Tate, was invited to speak on behalf of patients at a press conference hosted by House Speaker Nancy Pelosi and Senate Minority Leader Chuck Schumer, and attended by several other Congressional healthcare leaders. The conference was aimed at tackling ongoing efforts to erode the Affordable Care Act and threaten protections for patients with pre-existing conditions.
David spoke of his son, Lucas, diagnosed with acute lymphoblastic leukemia when he was only seven months old. At a time before critical patient protections were guaranteed by the Affordable Care Act, David was changing careers and had purchased a new plan only days before Lucas received the diagnosis. The insurer claimed Lucas’s cancer was a pre-existing condition and therefore ineligible for coverage, and David and his family and doctors had to fight them every step of the way.
After three days the advocates said they came away from the experience feeling energized and empowered to keep telling their stories and leading others back in their home states to do the same.
LLS is committed to advancing research and bringing new therapies to patients faster. But therapies can’t help if patients can’t access them. And none of our work would be possible without our amazing volunteer advocates, who bring these issues to life and make it real for the policymakers.
Follow #LLS4access on Twitter to learn more about our advocates' efforts this week. Do you want to be an advocate for LLS? To learn more visit www.lls.org/policy-advocacy
The steady pace of progress in treating patients with acute myeloid leukemia (AML), still one of the most deadly blood cancers, continued with today’s U.S. Food & Drug Administration’s second approval of a drug called ivosidenib (Tibsovo) that works for patients with a specific subtype of AML.
In another win for precision medicine, where therapies are matched to a patient’s specific genetic profile, the FDA approved ivosidenib for newly diagnosed patients 75-years-of-age and older with a genetic mutation known as IDH1. The FDA had approved ivosidenib in June 2018 for patients who had relapsed or did not respond to previous therapy.
While today’s approval of ivosidenib is based on a clinical trial in which newly diagnosed patients were treated with ivosidenib as a single agent, the drug continues to be tested in other trials, including LLS’s Beat AML Master Clinical trial, as a first-line therapy in combination with the chemotherapy drug azacitidine.
In 2016, LLS launched the groundbreaking Beat AML precision medicine study to test multiple targeted therapies simultaneously at multiple cancer centers around the country. Ivosidenib is being tested in Beat AML for newly diagnosed patients who are 60-years- of-age and older.
Today’s approval is based on findings from a phase 1 trial in which ivosidenib induced a 28.6% complete response (CR) rate and a CR plus CR with partial hematologic recovery (CRh) rate of 42.9%.
“For too long we’ve treated AML as a one-size-fits-all disease where it is really multiple subtypes of disease, and the outcomes for patients have been dismal,” said Louis J. DeGennaro, Ph.D., president and CEO of LLS. “Now, after four decades and millions of dollars invested, we are finally seeing results for AML patients that give us real reason for optimism.”
