Here at The Leukemia & Lymphoma Society (LLS), we applaud every advance for children with blood cancers. Today's reason to celebrate is the news that the U.S. Food and Drug Administration (FDA) expanded the approval of daunorubicin and cytarabine (Vyxeos®) to include treatment of pediatric patients aged one year and older with newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). This is a welcome and necessary advancement in support of some of our most vulnerable patients.
The therapy was previously approved in 2017 for adult patients who acquired AML after being treated for a previous cancer or whose AML developed after progressing from a diagnosis of myelodysplastic syndrome. LLS recognized this therapy's potential back in 2009 when it invested in it through its Therapy Acceleration Program® (TAP), which invests in cutting-edge companies working in areas of high unmet need for blood cancer patients. LLS partnered with Celator Pharmaceuticals, which Jazz Pharmaceuticals later acquired, on the clinical development of daunorubicin and cytarabine (Vyxeos®) for adults with AML.
The approval is supported by safety data from two trials conducted by the Children's Oncology Group (COG) and Cincinnati Children's Hospital (CCH), which established safety for relapsed/refractory patients. Both studies did report adverse reactions, including bleeding events, fever, and rash. The efficacy data was based on the CPX351-301 study in adults with secondary AML, which LLS TAP supported.
While we celebrate today’s news and what it means for children with AML and their families, and all the work being done to provide safe and effective treatments, LLS remains focused on how much more there is to do. Today, many children do not survive pediatric blood cancer, and survivors are often left with lifelong complications from treatment. When it comes to AML, the five-year survival rate for children younger than 15 years old diagnosed is only 68.7 percent.
Children have been treated with a one-size-fits-all approach for too long, despite cancer behaving differently in children than in adults. For many childhood cancers, chemotherapies developed decades ago remain the standard of care and simply don’t work well enough. In this era of precision medicine – giving the right treatment to the right patient at the right time – it’s critical for children to receive new therapies designed just for them.
LLS is determined to usher in a new era of drug development for pediatric blood cancers that puts children at the center of their care. Through the LLS Children’s Initiative, we seek to shift the standard of care for children, moving them away from toxic chemotherapies and toward effective and safe precision medicine treatments that target their cancer without harming the rest of their bodies. LLS is currently laying the groundwork for LLS PedAL, the first global precision medicine clinical trial for children with relapsed acute leukemia, which is being informed by its success with the Beat AML® Master Clinical Trial that was launched in 2016 for newly diagnosed AML adult patients 60 or older. Further, LLS is funding more than 30 research grants focused on deepening our understanding of the unique genetic causes and molecular biomarkers of pediatric blood cancer and how best to target them.
LLS is striving to raise $100 million for The LLS Children’s Initiative, which is a multi-year collaboration to expand our investment in leading-edge research, provide a comprehensive array of free information, resources, and financial support for affected children and families, and support policies that break down barriers to accessing care and developing new treatments.
Our goal is not only for children to survive blood cancer but for them to thrive in their lives after treatment.
Chimeric Antigen Receptor (CAR) T cell-therapy is on a roll. Today marks the seventh approval of CAR T therapy since the first approval in 2017. While all prior approvals with CAR T have directed the engineered T-cells to CD19, a marker on the surface of malignancies derived from B-cells, this is the first approval of a B-cell maturation antigen (BCMA)-directed CAR T. Idecabtegene vicleucel or ide-cel (Abecma) is the first approval of a CAR T for multiple myeloma. This approval comes on the heels of two new indications for CD19-directed CAR T: axicabtagene ciloleucel (Yescarta®) to treat resistant forms of indolent non-Hodgkin lymphoma, as well as the first approval of new CD19-directed CAR T, lisocabtagene maraleucel (Breyanzi®), for resistant forms of aggressive non-Hodgkin lymphoma.
LLS takes special pride in FDA approvals for CAR T therapies. Our initial investment in CAR T in the 1990’s, when CAR T, and indeed immunotherapy to treat cancer was in its infancy, has turned into a game-changing therapeutic giving new hope to patients with limited treatment options and often very poor prognoses. Through LLS academic grants and our Therapy Acceleration Program® (TAP) investment in biotechnology companies of over $50M in the past 30 years, LLS has been instrumental in bringing four CAR T-therapies to patients: axicabtagene ciloleucel (Yescarta®), tisagenlecleucel (Kymriah®), brexucabtagene autoleucel (Tecartus™) and liso-cel (Breyanzi®).
CD19-directed CAR T therapy is now approved to treat a range of B-cell malignancies including childhood B cell acute lymphoblastic leukemia and adult large B cell lymphoma, primary mediastinal large B cell lymphoma, mantle cell lymphoma and follicular lymphoma. These therapies have provided significant complete response rates that can last for years. The therapy may actually eradicate the disease yielding cures; the duration of the effect is still being evaluated as some patients have been cancer-free for nearly a decade.
Ide-cel is the first CAR-T that targets a different protein
Ide-cel works by targeting a protein called BCMA that plays a key role in multiple myeloma. The FDA approval was based on results from the phase 2 KarMMa study, which treated 127 patients with advanced forms of multiple myeloma. While multiple myeloma care and outcomes have improved, the disease remains incurable and patients like the ones in the KarMMa study, whose cancer has progressed despite treatment with at leastthree previous therapies, face poor survival rates.
The majority (72%) of patients in the trial partially or completely responded to ide-cel treatment, with 28% having a complete response—disappearance of all signs of multiple myeloma. Among those with a complete response, 65% remained in complete response for at least 12 months. The known side-effects for CAR T therapy were reported for ide-cel with marked cytokine release syndrome (CRS) and CAR T cell-associated neurotoxicity, occurring in 85% and 28% of patients, respectively, both of which were usually transient.
Multiple myeloma is most common among older patients who also face the worst prognosis and often have limited treatment option. Ide-cel was similarly effective in patients 65 and older, and even in those 70 and older, as it was in the overall study group. Perhaps most importantly, patients treated with ide-cel had improved quality of life. They reported meaningful improvements in most symptoms and their ability to perform day-to-day functions.
About multiple myeloma
Multiple myeloma is a cancer derived from a specialized type of white blood cell called a plasma cells. Such malignant cells proliferate uncontrollably leading to impairment of normal blood cell function, and in advanced cases leads to kidney impairment and bone destruction. While the disease is considered incurable, and the relative five-year survival rate for patients diagnosed with multiple myeloma in the US is approximately 50%, the addition of multiple new FDA-approved therapies to treat the disease are likely to increase overall survival rates in the future.
In 2021, there were 34,920 new cases of multiple myeloma associated with 12,410 deaths in the US. This accounts for approximately 20% of all new cases and deaths from blood cancers in the US. Myeloma is the second most common blood cancer in the U.S. and the most prevalent among African Americans. It is also the hematologic malignancy with the greatest racial disparity in incidence and prevalence; Blacks are not only at twice the risk of developing this rare and incurable cancer when compared to white Americans and other ethnic groups, they are also more likely to be diagnosed at a younger age.
In response to these inequalities, LLS launched a national outreach program in 2017 called “Myeloma Link” to educate African Americans about myeloma, and to help patients access optimal care, and navigate the treatment landscape more effectively.
LLS is looking to the future for better myeloma care and improved CAR-T options
While today’s approval is a step forward, we believe blood cancer is curable and we pledge to be unstoppable in our quest. We have 22 currently active grants focused on multiple myeloma supporting world-class researchers studying a range of novel treatment options.
We also support the power of partnerships. LLS Specialized Center of Research (SCOR) grants are designed to bring together established investigators to foster new interactions and cooperation to speed development of innovative strategies and approaches to blood cancers. In January 2020, LLS activated two SCOR grants investigating the use of CAR-T in multiple myeloma, to Carl June M.D., at the University of Pennsylvania and Madhav Dhodapkar MBBS, at Emory University in Atlanta, investing a combined $7.5M into their promising research.
LLS has also been at the forefront of CAR-T research and that is where we remain. Our current focus is on research to make CAR-T available for more types of cancer, by expanding the proteins targeted, and to make it less costly and quicker to administer. To speed the process and lower costs, LLS-funded researchers are working on “off the shelf” CAR T-therapies that use donor T cells instead of having to harvest and re-engineer each individual patient’s T-cells before reinfusing them.
We are also supporting research into immunotherapies using other parts of the immune system—beyond T cells—to express the Chimeric Antigen Receptor that gives CAR its name. Researchers are finding new ways to add the CAR receptor, which helps immune cells find and kill cancer cells that use natural killer (NK) cells or macrophages. These cells may provide longer lasting anti-tumor activity than traditional CAR-Ts and may also be useful for treating diseases beyond cancer.
We often connect one name to major scientific discoveries. Alexander Graham Bell and the telephone or Thomas Edison and the light bulb, among many others. But the reality is that medical breakthroughs are almost always based on years of research, collaboration, information sharing, and stepwise clinical trials that test the safety and efficacy of novel and re-purposed treatments over years. LLS has been committed to this process for more than 70 years, but today we’re also finding ways to speed it up, and the pace of new immunotherapies is proof of our—and the entire field’s—success.
In honor of Myeloma Awareness Month in March, The Leukemia & Lymphoma Society (LLS) is shining a light on how we champion myeloma cures and care. For Jennifer Flowers, who was diagnosed with multiple myeloma in 2008, our free education and support services and the powerful sense of community at our Light The Night events have made all the difference. Motivated to help other blood cancer patients and families, Jennifer has held several volunteer roles with LLS, including serving as an Honored Hero, Light The Night Leadership Committee Chair and Lead Team Captain, and a Patti Robinson Kaufmann First Connection Program Volunteer.
Today, Jennifer generously gives her time and talent to our Myeloma Link education and outreach program. Black Americans have twice the incidence of myeloma as white Americans and are less likely to have access to timely, optimal treatment and care. Together with our staff, volunteers, and supporters, LLS is dedicated to changing this. Offered in 13 cities across the country, Myeloma Link directly connects Black patients and caregivers with trusted, free myeloma information and support, as well as treatment and care. Since its inception, the program has reached nearly 30,000 individuals.
Recently, we had the opportunity to catch up with Jennifer on her cancer experience, commitment to giving back, and advice for patients and families.
As a volunteer, you’ve helped raise critical awareness and funds by sharing your powerful story and connecting with other patients and families. Can you take us through your cancer experience – before, during, and after your diagnosis and treatment?
Before I was diagnosed, I had been experiencing tiredness and pain in my left pelvic area that led me to seek medical attention. My diagnosis came during an especially tough year for my family. In the first part of the year, my mother was diagnosed with non-Hodgkin lymphoma. In the second part, my father was diagnosed with metastatic colon cancer. And in the third part, I was diagnosed with multiple myeloma. As a young, health-conscious, professional woman who exercised four times a week, I was stunned by my diagnosis. But with faith and support from family and friends, I summoned all my strength for the fight of my life.
After I was diagnosed, I endured multiple rounds of chemotherapy for a year. I then had an autologous stem cell transplant where my own stem cells were harvested and reintroduced into my body on January 8, 2010. This date is my second birthday. Receiving the transplant granted me a second chance at life. It saved my life, but it also threw me into the scariest part of my entire cancer experience. This resulted in an extended hospital stay followed by radiation treatments.
During my treatment, I experienced side effects like bone pain in my left hip and pelvic area. Currently, I am in remission and take a maintenance drug every other day because there are still traces of the multiple myeloma in my body. I also still experience bone pain from time to time.