Mantle cell lymphoma (MCL) has historically been difficult to treat and has had poor outcomes due to its aggressive nature and a lack of curative therapies. Although patient outcomes have improved with the development and US Food and Drug Administration (FDA) approvals of novel treatments, unmet needs remain, and there is still a long way to go to improve long-term survival among individuals with MCL.

There are 3 major unmet needs in MCL. The first is the effective treatment of older patients, the second is the management of high-risk MCL, and the third—and biggest—is the incurableness of MCL outside of allogeneic stem cell transplant (ASCT).

Many of the treatments that we offer can be difficult for older patients to tolerate or can even be contraindicated in older individuals, those with medical comorbidities, and those with frailty. Some older patients cannot tolerate any chemotherapy, let alone high-dose chemotherapy and ASCT. So, finding nonchemotherapy regimens is very important for upfront treatment and following relapse. Clinical trials are exploring nonchemotherapy-based combination therapies, including in older patients with medical comorbidities. I am looking forward to seeing the long-term results so that we can hopefully have new treatment options for these patients.

An inability to tolerate chemotherapy-based regimens can be seen as an issue of access (ie, an older patient’s lack of access to effective therapies for MCL). Another access-related issue for patients is one of cost. Some highly effective treatments for MCL, such as CAR T-cell therapy, are very expensive. Others involve potentially indefinite therapy, such as BTK inhibitors alone or in combination with other drugs, which can be very expensive when used over a long period. However, with an incurable disease such as MCL, even if the therapies are expensive, it is often worth the investment for patients who can tolerate the treatment and achieve long remissions. That is to say that these therapies can be cost-effective.

Further to this point, although age can be a contraindication to high-dose chemotherapy and ASCT, it is not necessarily a contraindication to CAR T-cell therapy. The toxicities associated with CAR T-cell therapy are not necessarily more challenging or more significant for older patients. They are also typically manageable and reversible, and they occur within a short window following the CAR T-cell infusion in the vast majority of patients. Since CAR T-cell therapy seems to offer the longest periods of remission of any therapy other than upfront chemotherapy, it is a very good option to offer to our older patients to help them achieve longer survival.

High-risk MCL, specifically MCL with TP53 mutations or MCL that is refractory to several lines of therapy, is very challenging to treat, making the treatment of this population a clear unmet need in the field. Patients who either do not respond to chemoimmunotherapy or relapse soon after tend to progress quickly on BTK inhibitors. Further, unlike patients with other incurable lymphomas, such as follicular lymphoma and marginal zone lymphoma, who can live with their disease for decades and whose disease alternates between periods of quiescence and activity, individuals with MCL do not have that degree of longevity and MCL can shorten the overall life span of younger and middle-aged patients. Thus, finding therapies that can change the natural disease course by being curative or extending survival is a really important challenge.

Treatments such as CAR T-cell therapy and bispecific antibodies are leading to much longer remissions among high-risk patients and among those with multiple relapses, so these are very exciting options for our patients. We do not have long enough follow-up with CAR T-cell therapy or bispecific antibodies to understand whether a subset of patients could be cured, but we are certainly seeing people remain in remission for 5 years after treatment with CAR T-cell therapy, which is encouraging. We hope that a subset of patients will be cured.