Encouraging Treatment Development Ongoing for Indolent B-Cell Lymphomas

Previous decades have allowed for the development and approval of a number of new agents for the treatment in 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, there are novel agents including chimeric antigen receptor (CAR) T-cell therapies, PI3K inhibitors, lenalidomide (Revlimid), rituximab (Rituxan), and more, which offer the chance of long-term survival and remission for patients with indolent B-cell lymphomas.

Ann LaCasce, MD, MMSc, associate professor of medicine at Dana-Farber Cancer Institute, director of the Dana Farber/Mass General Brigham Fellowship in Hematology/Oncology, notes that rituximab, which came into the field approximately 10 years ago, was approved as the first immunotherapy drug that lengthened overall survival in patients to close to 20 years or more. Its impact has led it to be used within every line of therapy, as well as in combination with agent that are in development.

With the 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 in the field, according to LaCasce.

In an interview with Targeted Oncology^TM, LaCasce, discussed how the landscape for patients with indolent B-cell lymphomas has changed positively over the past decade.

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

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

What is available to patients with indolent B-cell lymphomas and how does the current landscape look?

It's looking really great. CAR T-cell offers the possibility of long term remission. We don't have long enough follow up to know whether those responses at 2 years will be durable, but we're hopeful. In the meantime, we have PI3K inhibitors which have sort of unique toxicities that you can customize for your patient, pick the agents that seem best. One is IV, 1 is oral, 1, copanlisib can cause high blood pressure and diabetes, so in that setting, you don’t want to pick a patient who has those issues at baseline.

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

How have recent and ongoing advances in this field changed the way these patients are treated? What are you most excited about?

I'm particularly excited about the CD20 bispecific antibodies. There are 4 agents that are currently in clinical trials. There have been a lot of debates about how the activity of these agents will compare to CAR T-cell therapy? We know they can cause cytokine release syndrome and inflammatory-like reactions, but they don't appear to have the neurologic toxicity that you can see with CAR T. Though with CAR T, it's less than with aggressive lymphoma in terms of the rates of neurotoxicity.

These are available off the shelf so that you don't have to collect cells and send them for manufacturing, and I think that is very appealing. These drugs are being combined with all kinds of agents including rituximab and lenalidomide and other novel agents. I think that'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 have lots of good options since rituximab was approved back in the late 1990s. We've seen the overall survival really, dramatically lengthen. So this is just all good news for patients, you know, both in terms of tolerability as well as, you know, activity and efficacy.

What issues still have to be dealt with in this space?

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

The major unmet need is in the relapsed refractory setting. I would like to see us getting away from chemo in the frontline setting and to use some of these more novel drugs so that we don't expose people to therapies that may cause stem cell damage or other problems down the line.

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

I would like to reach out to us in academics. We are very happy to join forces and share patients. If you are thinking about trying 1 of these agents, if you don't have a lot of experience, feel free to reach out. We only treat one disease, lymphoma, which is many different diseases, but it's much easier for us to keep on top of the lymphoma data whereas community oncologists have to treat such a wide spectrum of diseases. It's a very hard job and with all this explosion of new drugs, I can't imagine what it would be like to try to apply this data in real time to patients. I think the message is always reach out and we're always available and happy to help.