MRD and the Changing Myeloma Landscape
By Susan Bobulsky, SVP, Diagnostics, clonoSEQ & Jenny Ahlstrom, Founder, Myeloma Crowd
In March 2021, the blood cancer community celebrated a big win for those living with multiple myeloma (MM) with the FDA approval of Abecma® (idecabtagene vicleucel), the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of adult patients with relapsed or refractory MM after four or more prior lines of therapy. MM is a blood cancer in which abnormal plasma cells build up in the bone marrow and form tumors in bones. Despite advances in treatment, MM remains an incurable disease.
Innovative treatments such as Abecma are critical for moving the needle forward in the MM treatment landscape. Abecma is made from a patient’s own T cells, the adaptive immune system’s first responders to detect any virus, which are reprogrammed to find and destroy specific target cells.
The clinical trials that evaluated Abecma assessed minimal residual disease (MRD) using Adaptive’s clonoSEQ® Assay, the first and only FDA-cleared assay for minimal residual disease (MRD) in select blood cancers, including MM. MRD refers to the small number of cancer cells that can stay in the body during and after treatment. An MRD-positive test result means that disease was still detected after treatment, while an MRD-negative result means no disease was detected after treatment. Because MRD is a direct measure of disease, assessing its presence and level is a powerful way to evaluate a patient’s response to treatment, dynamically evaluate prognosis, monitor remissions, and detect early signs of potential recurrence.
We sat down with Jenny Ahlstrom, a MM patient and founder of the advocacy organization Myeloma Crowd, to discuss what the approval of Abecma means for the MM community. Jenny also provided insight into the role of MRD testing in treatment decision-making, its use in clinical trials, and the future treatment landscape for MM.
Q: What does the FDA approval of the first CAR T cell therapy for MM mean for patients?
Jenny Ahlstrom: The Myeloma Crowd was an early funder of CAR T, and the FDA approval of the first CAR T cell therapy for the treatment of patients with relapsed/ refractory MM who have been treated with four or more prior lines of therapy is a watershed moment for the community.
T cells are an important part of the immune system, and the use of a patient’s own immune cells to fight MM opens up a whole new world. This approval represents a new way of thinking about how to treat MM patients, many of whom relapse following initial therapy.
Q: How will having a CAR T cell therapy for MM change the treatment landscape and outcomes for patients? What’s next?
Jenny Ahlstrom: I think eventually CAR T cell therapy will be moved up earlier in the treatment paradigm. Now that we have seen such high response rates with CAR T cell therapy, we will next want to determine how to extend and maintain them. We will also want to evaluate whether earlier use of CAR T cell therapy can maintain longer remissions, and if additional therapies added to the treatment regimen following CAR T cell therapy can help patients maintain a response. There is more research to be done, but with so many innovative treatments available now for MM, I believe we will find the best treatment sequencing and combinations for patients over time.
Q: Why is it important for patients to know about MRD and MRD testing?
Jenny Ahlstrom: MRD is a tool, and the more tools we have in the toolbox for managing patients with cancer, the better!
Continuously monitoring patients for disease progression during and after treatment can provide meaningful information and inform treatment decisions. Whether a patient was just diagnosed or has been through multiple prior therapies, MRD testing gives hematologists/ oncologists a personalized way to track the patient’s individual response to treatment. The fact that Abecma can help patients achieve MRD negativity even after 4+ lines of prior therapy demonstrates that MRD testing has value for monitoring depth of response at all points throughout the treatment continuum.
Patients always want to know if they are in jeopardy of relapsing and what can be done about it, but they don’t want to wait until a full relapse. They want to know right away. With MRD testing, their physician can see if they may be heading toward a relapse and take immediate action to develop a personalized treatment plan, so their disease doesn’t continue to grow.
For patients in remission, periodic MRD testing can provide peace of mind, especially given how prevalent relapse is in this patient population. MRD testing also can be helpful in guiding patients who want to stop receiving maintenance therapy, which can be associated with side effects and financial costs.
Q: What other benefits does MRD testing provide to patients?
Jenny Ahlstrom: The more data patients and physicians have, the better. With MRD results in hand, hematologists/oncologists can show patients how their immune system is responding to treatment. With this data, doctors can have more informed conversations with patients about treatment goals and effectiveness and future prognosis – and patients are better equipped to participate in the discussion about managing their disease.
Q: What is the level of awareness around MRD within the MM patient community?
Jenny Ahlstrom: Patients newly diagnosed with MM are overwhelmed and getting information to them is challenging. They must make critical decisions in a matter of days. They must self-advocate. They need to watch their numbers. Furthermore, if they are not being treated at an academic center, where MRD testing is more common, they may not be familiar with MRD or even know to ask for it. Our goal at Myeloma Crowd is to reach these patients at the beginning of their journey with the disease so we offer a wealth of resources.
Q: As the treatment landscape for blood cancers continues to evolve, what role will MRD testing have in clinical practice and in clinical trials?
Jenny Ahlstrom: You’ll likely see today’s “standard” therapy for newly diagnosed patients change over the next few years to incorporate more immunotherapy up front. Treatment is becoming more nuanced, and MRD testing is a tool to help with that. As the number of effective treatment options continues to expand, the number of patients who reach late lines of therapy is growing, making the ability to confirm deep and durable MRD-negative responses in the salvage setting increasingly important. MRD testing is not only a reliable method for understanding a patient’s prognosis and outcome, it also may be important in helping sequence CAR T and other innovative treatments in the right way to prolong survival.
MRD is also an important tool that could benefit clinical trial design and help speed up studies. When MRD is used as an endpoint, it can provide results about whether a patient is responding to treatment in a much shorter timeframe than using overall survival as an endpoint – in 3 to 5 years vs. 8 to 10 years – and help us learn more, faster.