Encourage the development of ongoing treatments for indolent B-cell lymphomas


Ann LaCasce, MD, MMSc, ​​discussed how the landscape of patients with indolent B-cell lymphomas has changed for the better over the past decade.

The previous decades have seen the development and approval of a number of new agents for the treatment of patients with indolent B-cell lymphomas, creating a positive outlook on its current landscape.

While the only treatment for this patient population was once chemotherapy alone, newer agents exist, including chimeric antigen receptor (CAR) T-cell therapies, PI3K inhibitors, lenalidomide (Revlimid), rituximab ( Rituxan), and more, which offer the possibility of long-term survival and remission for patients with indolent B-cell lymphomas.

Ann LaCasce, MD, MMSc, ​​associate professor of medicine at the Dana-Farber Cancer Institute, director of the Dana Farber/Mass General Brigham Fellowship in Hematology/Oncology, notes that rituximab, which entered the field about 10 years, was approved as the first immunotherapy drug that lengthened overall patient survival to almost 20 years or more. Its impact has led it to be used in all lines of therapy, as well as in combination with agents under development.

With research and clinical trials examining other treatment options, including CD20 bispecific antibodies, understanding the activity and efficacy of these agents will allow for even more updates from the field, according to LaCasce.

In an interview with Targeted OncologyMTLaCasce, explained how the landscape of patients with indolent B-cell lymphomas has changed for the better over the past decade.

What was discussed at NCCN regarding the management of patients with indolent B-cell lymphoma?

LaCasce: My part of the presentation for the NCCN conference was on the treatment of relapsed refractory follicular lymphoma. We have a number of new agents and are primarily focusing on those that have been approved as part of the third line. [Some include] PI3K inhibitors, we discussed copanlisib [Aliqopa] and umbralisib [Ukoniq]as well as tazemetostat [Tazverik], and CAR T-cell therapy. We spent some time in the second-line situation talking about lenalidomide plus rituximab as a good option for patients who progressed after initial treatment.

What is available for patients with indolent B-cell lymphoma and what does the current landscape look like?

It looks really awesome. CAR T-cell offers the possibility of long-term remission. We don’t have enough tracking to know if these 2-year responses will be sustainable, but we’re hopeful. In the meantime, we have PI3K inhibitors that have kind of unique toxicities that you can customize for your patient, choose the agents that seem best to you. One is IV, 1 is oral, 1 copanlisib can cause high blood pressure and diabetes, so in that context you don’t want to pick a patient who has those issues to begin with.

Tazemetostat is particularly active in patients who have mutated EXH2, but it is also an agent that has similar progression-free survival in the mutated group, and is a very well tolerated option. Then, many clinical trials examine these agents in combination with specific antibodies. I think this is an area where we will continue to experience substantial growth over the next few years.

How have recent and ongoing advances in this area changed the way these patients are treated? What excites you the most?

I’m particularly excited about CD20 bispecific antibodies. There are 4 agents currently in clinical trials. There has been much debate about how the activity of these agents will compare to CAR T-cell therapy? We know they can cause cytokine release syndrome and inflammatory type reactions, but they don’t seem to have the neurological toxicity that you can see with CAR T. Although with CAR T it’s less than with aggressive lymphoma in terms of neurotoxicity rates.

These are available off-the-shelf so you don’t have to collect cells and send them off for manufacturing, and I think that’s very appealing. These drugs are combined with all kinds of agents, including rituximab and lenalidomide and other new agents. I think it’s going to be very exciting to see how this all plays out.

And it’s all good for our patients. Follicular lymphoma is a disease that has a long natural history, we’ve had a lot of good options since rituximab was approved in the late 1990s. We’ve seen overall survival really, dramatically lengthen. So that’s just good news for patients, you know, both in terms of tolerability as well as, you know, potency and efficacy.

What issues still need to be addressed in this space?

For patients who have really refractory disease, who may have had CAR T cells and the disease has come back, is a difficult group of patients to treat, these are patients who have low blood counts as a result things like CAR T, I think the big issue is the cost of these new drugs. We have many patients whose insurance coverage does not provide adequate coverage for these oral medications that people take on average for about a year or more.

The main unmet need is for the relapsed refractory environment. I wish we would move away from chemo on the front lines and use some of these newer drugs so that we don’t expose people to therapies that can damage stem cells or other problems down the road.

What advice do you have for community oncologists about treating lymphoma with the new agent sleuth we have today?

I would like to join us in academics. We are very happy to join forces and share patients. If you are considering trying one of these agents, if you do not have much experience, do not hesitate to contact us. We treat only one disease, lymphoma, which encompasses many different diseases, but it is much easier for us to keep up to date with lymphoma data when community oncologists have to treat such a wide range of diseases. It’s very difficult work and with all this explosion of new drugs, I can’t imagine what it would be like to try to apply this real-time data to patients. I think the message is always reaching out and we are always available and happy to help.


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