New Treatment Options for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

February 25, 2021

If you or someone you love is facing a diffuse large B-cell lymphoma (DLBCL) diagnosis, and the lymphoma has either relapsed or has not responded to initial treatment (refractory DLBCL), you may be wondering what your next steps for treatment look like. What are your options? How do you talk with your physician about your choices and determine which option is best for you? Are there new treatments available?

In a one-hour video interview, Cancer Support Community’s CEO Linda Bohannon, RN, BSN, MSM, spoke with Ohio State University hematologist Kami Maddocks, MD, about diagnosing and treating lymphomas, including DLBCL. They also discussed:

  • Several new treatment options for relapsed and refractory DLBCL
  • Testing procedures used to detect and monitor DLBCL
  • Questions to discuss with your physician when reviewing treatment options
  • Clinical trials as an additional option for patients with lymphoma
  • Self-care during treatment

Read on to get an overview of the discussion. Then watch the video interview for an in-depth look at new treatment options and more on DLBCL.


Initial Treatment for DLBCL and Other Aggressive Lymphomas

Dr. Maddocks specializes in treating people with blood cancers, including B-cell cancers like non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL). B-cell lymphomas account for about 85% of non-Hodgkin lymphoma cases in the U.S. Most B-cell lymphomas are either DLBCL or follicular lymphoma. Roughly 1 out of every 3 cases of non-Hodgkin lymphoma is DLBCL.

Lymphomas can be indolent (slow growing) or aggressive. DLBCL is an aggressive form of lymphoma, explained Dr. Maddocks, who conducts research on new lymphoma therapies. “Aggressive lymphomas tend to come on quickly, and they need to be treated soon after they are diagnosed,” she said. “In general, they are potentially curable with treatment and potentially curable at relapse.”

With aggressive lymphomas like DLBCL, somewhere between 60% and 70% of patients are cured with their initial chemoimmunotherapy treatment, said Dr. Maddocks. But for the remaining patients, 1 of 3 things generally happens:

  • The lymphoma initially responds to treatment and there is no detectable lymphoma, but then it comes back in the future (a relapse)
  • Some, but not all, of the lymphoma goes away
  • The lymphoma doesn’t respond to the first treatment and it continues to grow

When it comes to treating aggressive lymphomas like DLBCL, the initial treatment approach is generally the same as for other lymphomas, said Dr. Maddocks. Most aggressive lymphomas are treated with a combination of chemotherapy and immunotherapy when the patient is first diagnosed. Occasionally, radiation therapy might also be used after chemotherapy treatment.


Making Treatment Decisions for Relapsed or Refractory DLBCL

When an aggressive lymphoma remains or relapses after initial treatment, Dr. Maddocks explained that there are different treatment options to consider. The options include targeted therapies, immunomodulatory therapies, stem cell transplant, or CAR T cell therapy.

When considering the different options, noted Dr. Maddocks, “you have to look at the patient’s disease and characteristics. So, how old is the patient? What other medical problems does the patient have? Do they have heart disease? Lung disease?”

The answers to these types of questions help the physician understand whether a patient may experience problems tolerating a certain treatment like chemotherapy. It’s also important to understand the patient’s own preferences, said Dr. Maddocks. As a patient, questions to discuss with your physician include:

  • Are you concerned about certain side effects?
  • How often would you need to come to the clinic to get treatment?
  • Do you prefer to take a pill at home, if that’s an option?
  • How did you tolerate your first treatment? Did you have a lot of side effects?

“You have to think about all those things when you are deciding what to give [patients] after their first treatment,” explained Dr. Maddocks. “Some people have side effects that remain from their first treatment, such as peripheral neuropathy [damage to the nerves] — that’s a common thing from some of the different chemos.” If that’s the case, she noted, a physician may not give the patient a drug that could worsen the condition, if there are other options available.

“Patients should always tell their doctor if they are having side effects,” said Dr. Maddocks. “Some [patients] are afraid to tell their side effects because they don’t want their treatment to change, but it’s really important to tell your doctor, because sometimes they might be able to make a change that will not affect the outcome but can make the side effect better. So, the lines of communication go both ways, from the patient to the physician, and the physician to the patient. [That’s] very important.”


New Treatment Options to Consider

For patients who don’t go into remission after their second therapy, or who get a stem cell transplant and relapse after that procedure — or whose bodies cannot tolerate a stem cell transplant — Dr. Maddocks noted that there’s a therapy available called chimeric antigen receptor T-cell therapy. Also known as CAR T cell therapy, this is a relatively new therapy that was first approved about 3 years ago. “This is considered an immune therapy, but instead of collecting your stem cells for the transplant, they collect your T cells — so another one of your immune system cells. They are sent off and reengineered or tweaked, they are sent back, and you’re given those [cells] back.”

The job of these reengineered T cells is to recognize the lymphoma as bad and activate your body to attack the lymphoma, explained Dr. Maddocks.

But if a patient doesn’t have access to a facility that offers CAR T cell therapy, or if a patient isn’t able to tolerate the side effects of that therapy, there are other new treatment options available.

“Since the approval of CAR T therapy, we’ve seen the approval of 3 other different drugs or regimens [for] relapse or refractory diffuse large B-cell lymphoma,” said Dr. Maddocks. “So, it’s an exciting time for lymphoma patients because, in the last few years, we’ve seen so many options that they didn’t have before.”