Jia Ruan, MD, PhD, Professor of Clinical Medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medicine, spoke with Blood Cancers Today about novel treatment combinations and incorporating novel agents in frontline treatment, as well as some of the challenges that remain in the treatment of mantle cell lymphoma (MCL).
Can you give a brief overview of what you discussed during your session?
We talked about the heterogeneity in terms of the biology and how that is guiding us determine personalized treatment based on the disease and patient characteristics. Secondly, we talked about new treatments on the horizon, especially the introduction of new agents, particularly in the initial therapy settings that add to the current chemo-immunotherapy or exploration of chemotherapy-free options. Thirdly, we talked about patients who may develop resistance and what kind of therapeutic options they have. Examples of that include CAR T-cell therapy, antibodies that target novel surface molecules such as ROR1, and also novel agents such as bispecific antibodies that bring together CD20-positive B cells with anti-tumor CD3 T cells. Finally, we talked about the emerging options for MCL, including combinations of treatment to combine with BTK inhibitors and that we hope could overcome resistance and provide therapy for a patient who has high-risk disease.
What are some challenges that still persist in this field?
The new developments are really geared toward how we can treat patients with very high-risk conditions such as TP53 mutations and those who come in with very intrinsic high resistance to standard chemo-immunotherapy, but perhaps also to combinations of biological agents such as BTK inhibitors and others. The challenge is coming up with good combinations that are effective but also have low toxicity that can provide very durable responses. Another important challenge is development of an algorithm to sequence treatment. If disease becomes resistant to one therapy, what would be the next appropriate options? That will depend on their previous treatment and on the biological composition of the disease or whether they have developed any kind of new mutations (based on next-generation tumor DNA sequencing).
What is next in the field?
It will be to learn from the new data on novel agents, including reversible BTK inhibitors such as pirtobrutinib and alternative tumor targets, such as anti-ROR1 antibody and also bispecific antibodies because it’s an attractive form of immunotherapy but it’s also coming with advantages such as being off the shelf and ready to go (compare to CAR-T). Bispecific antibodies have demonstrated very impressive preliminary efficacy for patients with relapse and resistant MCL. The question is, can we try to develop earlier use of these novel agents for patients who maybe have TP53 mutations and become resistant to BTK inhibitors? Depending on the safety profile, we may want to do an exploratory investigation, for example to see if we can provide that as earlier or initial therapy for a patient with very high-risk disease.