Those diagnosed with blood cancers previously relied on treatment options such as chemotherapy and radiation that, while often effective, also indiscriminately attack healthy cells in the body.
With the advent of the first-ever targeted therapy that zeros in on specific cells two decades ago, the treatment landscape for people with rare, serious blood diseases was completely transformed.
Since then, the development of innovative treatments such as bispecific antibodies and antibody drug conjugates (ADCs), as well as the use of alternative clinical trial endpoints such as minimal residual disease (MRD), have shown their value and potential in improving health outcomes for patients.
Of course, with the rapid pace of innovation also comes an even greater urgency to advance these therapies so that every patient diagnosed with blood cancer has an effective treatment option.
Dr. Nancy Valente, Senior Vice President and Global Head of Product Development Hematology at Genentech, has helped lead the company’s hematology portfolio for nearly 20 years. As a board-certified hematologist and medical oncologist with years of clinical experience, she has her own perspective on the key advances that have recently shaped the hematology treatment landscape and innovations on the horizon that could have a significant impact in the years to come.
Unique cancers call for unique treatments
According to the World Health Organization, the term blood cancer is a broad one and comprises more than 100 different disease types, and reflects both the cell of origin and the unique biology.
The clinical presentations, locations of the tumor, cell types, symptoms, and prognoses vary widely and affect treatment protocols and disease progression.
While many types of aggressive blood cancers were previously considered fatal, in recent years, clinical and genomics research have uncovered valuable insights about tumor biology and have provided a significant opportunity to develop new treatments.
“In blood cancer, it’s a lot easier to study the biology of the disease over time because the cancer cells are in circulation,” according to Valente. “We can gather new insights from these large clinical data sets combined with genomic data to inform our research and the development of new therapies.”
Decades of R&D have advanced novel targeted therapies
Since the approval of the very first targeted therapy for any disease, cancer researchers have spent decades advancing this approach and recently developed novel, targeted therapies that show the value of chemotherapy-free or fixed-duration options.
One such treatment option induces apoptosis, or cellular self-destruction, which unlike other targeted therapies that typically only slow cell growth, leads to irreversible cell death. As one component of treatment regimens for both acute and chronic forms of leukemia, this treatment, in combination with other medicines, can give some patients the option of forgoing chemotherapy altogether.
ADCs build on the idea of traditional targeted therapies and use antibodies to deliver potent chemotherapy to specific cell types. Genentech developed a first-in-class treatment for those with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), an aggressive form of blood cancer with limited treatment options.
“Our scientists continue to look at ways to harness this technology by combining other toxins or other types of therapies with an antibody and targeting this to cancer cells. We have a deep research effort in this area and are committed to evolving ADCs to find new treatments,” said Valente.
Both of these targeted treatments can be used as part of fixed-duration treatment regimens, meaning the treatment only needs to be administered for a specific amount of time, after which patients can still see their disease improve. Therapies that limit the duration of treatment allow people to preserve a high quality of life while still managing their disease.
Harnessing the power of bispecific antibodies
While immunotherapy-based approaches like check-point inhibitors have shown success for the treatment of solid tumors, and CAR-T cell therapies brought immunotherapy to blood cancers, T-cell engaging bispecific antibodies represent a novel immunotherapy approach that have already shown early potential for various blood diseases.
Bispecific antibodies bind to a protein on cancer cells with one arm and to an immune cell with the other, allowing the immune cell to detect and destroy the cancer cell.
Studies that Genentech shared through the American Society of Hematology (ASH) 2020 Annual Meeting for its investigational bispecific antibodies showed early, promising results for people with different types of B-cell non-Hodgkin’s lymphoma (NHL), as well as multiple myeloma (MM).
“Many patients cannot wait for the more complex immunotherapy approach of cellular therapy, but bispecific antibodies are an off-the-shelf product that’s ready when the patient needs it,” said Valente. “Bispecific antibodies seem to be very effective when given alone and they offer the opportunity to be used in combination with other immunotherapies, targeted therapies, and even current standards of care.”
Bispecifics have also shown their value in blood diseases beyond cancer. For example, Genentech developed the first bispecific antibody for the treatment of hemophilia A, a serious genetic disorder in which a person’s blood doesn’t clot properly. It is the first and only subcutaneous treatment for hemophilia A, providing a more convenient administration option for some patients.
A new path forward for MRD as an endpoint
Beyond novel targeted therapies, the use of alternative clinical trial endpoints could change the way treatment efficacy is assessed, potentially allowing new treatments to be made available to patients sooner.
Genentech has been particularly focused on advancing the use of MRD, which is the measurement of the depth of response to a treatment, or the degree to which the cancer is eliminated. While the concept has been around for decades, and it has the potential to indicate the degree to which cancer has been eliminated at earlier stages of treatment, only recently have laboratory technologies become sensitive enough to detect it.
Genentech is using an early MRD negative state as the sole primary endpoint in a clinical trial for patients with chronic lymphocytic leukemia (CLL).
“We know that if patients reach that state, they’re going to have a longer remission,” said Valente. “In collaboration with partners, clinicians, advocates, and the FDA, we hope to better understand how MRD as an endpoint can be used to advance therapies for all types of blood cancers.”
Personalizing the future of blood cancer treatment
As we look to the future, advancing personalized blood cancer treatments for each patient is key.
For starters, research in the emerging field of circulating tumor DNA (ctDNA), as well as biomarker testing, may yield valuable knowledge for advancing new targeted therapies for blood cancers.
Also, by assessing large sets of clinical and genomic data, there is potential to develop genetic profiles for individuals or groups of patients to guide optimal therapy selection.
To be successful, Valente believes utilizing artificial intelligence and machine learning will play a more significant role in this process.
“When you’re talking about big clinical data or genomic data and you want to crunch the numbers, you need machine learning to help you develop insights that aren’t obvious,” said Valente. “I think we are poised to use that to further our scientific understanding, drive development, and tailor therapies to patients. We are excited about what the future holds.”
To learn more: https://www.gene.com/topics/hematology