ASH annual meeting 2021 round-up

At the American Society for Hematology (ASH) Annual Meeting in December 2021, the most up-to-date research was shared on Follicular Lymphoma (FL), as well as other blood cancers. In this roundup, read about the biggest breakthroughs in treatment regimens for FL patients and other important updates.

CAR T-cell therapies show a good response in most FL patients

CAR T-cell therapies (patient’s own T cells engineered to attack B cells) have gained traction in recent years, after showing promising results in a range of B cell lymphomas. In Large B-Cell Lymphoma (a more aggressive lymphoma that can also develop in FL patients), the ZUMA-7 and TRANSFORM trials showed that CAR-T are better than the current standard of high dose chemotherapy with autologous stem cell support for those who relapsed soon after initial therapy, with expected but manageable side-effects.

In the ZUMA-5 and ELARA trials 90% of FL patients responded well to CAR-T. It is still too early to know precisely how long remissions will last, however, around 40% of patients relapsed within 2 years of treatment. Further research is underway to understand why some patients relapse, then how to prevent that, and how to better predict which patients would benefit most from CAR-T.

Bispecific antibodies may offer a more accessible option for FL patients in the future

Bispecific antibodies are designed to bind both B and T cells. This ultimately enables patients’ T-cells to target and kill the cancer B cells. Although these bispecific antibodies are still in the early phases of development, rapid progress means several look very promising in a range of lymphomas, including FL. Mosunetuzumab showed encouraging results in Relapsed/ Refractory FL patients. Some advantages to bispecific antibodies are that they may be more broadly available and easily administered compared to CAR-T.

Other promising therapies in the pipeline

The cancer cell death promoting drug venetoclax, and BTK inhibitors (particularly in combination with immunochemotherapy) have transformed treatment for CLL (Chronic Lymphocytic Leukemia), but are less active against FL. However, newer generations of both classes of drugs are being tested in FL. There are also other classes of drugs that are still in early development in FL, but well-worth keeping an eye on as clinical trials are underway.

Finding ways to better monitor disease progression and response to treatment

One reason patients relapse even after having responded well to a chosen therapy, is due to small numbers of lymphoma cells remaining in their bodies. This is referred to as Minimal Residual Disease (MRD). Over time, these can grow and lead to the lymphoma returning, needing further treatment. MRD can be measured in a tumour biopsy, the bone marrow or even blood.

In FL, MRD testing is still in its infancy compared to other blood cancers such as Multiple Myeloma, where MRD testing is often monitored during and after treatment to aid decision-making in therapy regimens. The biggest challenges are: testing the tumour tissue is often difficult and invasive for patients; and due to the slow-growing nature of FL, MRD blood markers are currently very hard or not possible to detect.

The good news is that the underlying biology of FL is being unravelled more and more, and together with exciting technological advances, the future for detecting and monitoring MRD in FL looks encouraging.