When it comes to the future of treatment for lymphoma, advances in areas such as genomics and immunotherapy are bringing significant progress. Managed Healthcare Executive (MHE) asked Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society (LLS), to offer an overview of current developments as well as a look forward.
MHE: How would you characterize the current situation in lymphoma treatment?
GN: Recently we’ve seen remarkable progress in lymphoma treatment, thanks to breakthroughs in immunotherapy, genomics and personalized medicine. For example, the FDA recently approved brentuximab vedotin (Adcetris) in combination with chemotherapy to treat patients newly diagnosed with advanced Hodgkin lymphoma. This innovative antibody drug conjugate replaces a particularly toxic chemotherapy in the approved treatment regimen, transforming the standard of care for this patient population for the first time in more than four decades.
MHE: Just how is immunotherapy changing the way we approach cancer treatment?
GN: Two groundbreaking CAR T-cell immunotherapies are now approved for certain patients with diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma (NHL): axicabtagene ciloleucel (Yescarta) and most recently, tisagenlecleucel (Kymriah). DLBCL is aggressive; in fact, many patients present with advanced disease at the time of diagnosis. These approvals not only bring new options to patients who do not respond to standard therapies, but also highlight the promise of immunotherapy as a game-changing therapeutic approach to add to our armamentarium.
MHE: What challenges remain?
GN: With the proliferation of new therapies, we need to be vigilant about evaluating clinical factors to understand which patients with lymphoma might benefit from what treatment options. Research on biomarkers predicting response is increasingly important as we consider combinations of therapies that will be costly both from a financial as well as physical point of view.
Additionally, the process of producing CAR T-cell therapies is cumbersome and can take a long time. The Leukemia & Lymphoma Society (LLS) is currently funding research to determine how to make these treatments faster, safer, and more effective for patients. It’s also important that we help patients understand their treatment options, including potential risks, and work with them to navigate the total cost of their care, both financial and physical.
MHE: Are there any types of lymphoma where there is reason to be especially optimistic for successful treatment outcomes?
GN: We’re seeing promising developments in the treatment of mantle cell lymphoma (MCL). Despite previous advances, patients with this disease often face a challenging prognosis. Even if the initial treatment works, the disease comes back in virtually all patients. The good news is, we know considerably more about the molecular basis of MCL now compared to 10 years ago and new research efforts are accelerating treatment options.
Beginning in 2013, the FDA approval of ibrutinib (Imbruvica), the first Bruton tyrosine kinase inhibitor, was key for MCL treatment. Building upon this work, the FDA approved acalabrutinib (Calquence) in October 2017 for patients whose cancer has progressed after receiving at least one prior therapy. These agents mark significant progress for patients with MCL.
Additionally, discoveries by Dr. Selina Chen-Kiang, professor of pathology, laboratory medicine, and immunology at Weill Cornell Medicine, have shown that a targeted drug effective in blocking the CDK4/6 enzymes responsible for cell division, might be effective in treating patients with mantle cell lymphoma. Dr. Chen-Kiang’s work has been supported by LLS for nearly two decades. Her discoveries have also helped lead the way to that therapy, palbociclib, receiving FDA approval in 2015 for breast cancer.
MHE: What progress do you foresee in improving lymphoma patients’ quality of life?
GN: Some exciting updates at the recent ASCO conference suggest that for follicular lymphoma patients, chemotherapy-free regimens might be equally as effective as traditional chemotherapy-containing regimens. The possibility of moving more patients to less toxic chemo-free regimens is very hopeful for the quality of life of patients with lymphoma.
Additionally, understanding minimal residual disease and finding less invasive ways to test for it will have two benefits for patients. First, understanding depth of response and early relapse might help us design early intervention/prevention strategies so we can intervene before patients have frank return of disease. Second, less invasive methods for testing using circulating cells or DNA might decrease the need for frequent biopsies of lymph nodes or bone marrow, improving the quality of life of patients.
MHE: Looking a few years ahead, what would you predict for the overall status of lymphoma treatment?
GN: The Leukemia & Lymphoma Society (LLS) is supporting exciting research in two areas. One, identifying the earliest stem cells that might be responsible for relapse, particularly in follicular lymphoma. If we can stop these cells from proliferating, we might get closer to cures in low-grade lymphomas. Two, exciting advances in biomarkers are revealing subsets within the classical pathologic subtypes of lymphoma. This science will lead to more personalized, targeted treatments in the years ahead. This personalized approach will require patients to have more in-depth molecular pathologic testing at diagnosis and emphasizes the critical importance of making the right initial diagnosis in lymphoma as the field is increasingly complex. Now, and in the years ahead, biomarkers will determine the best treatment regimen. I encourage healthcare executives to promote greater understanding and education of molecular diagnostics among providers, including sharing resources available to patients. Patients and caregivers who have questions or want to learn about their lymphoma diagnosis can speak to LLS’s Information Specialists at 1-800-955-4572 or at lls.org/support.