Published on July 15, 2020
New Treatments For Patients With Diffuse Large B-Cell Lymphoma
Diffuse large B-Cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma and is a cancer of the B lymphocytes. New drugs, combination therapies and even methods to bolster a patient’s immune system are giving doctors and clinicians increasing hope of successfully treating several types of DLBCL.
“Just in the last five years or so, we have multiple more options,” said Dr. Sarah Rutherford, a lymphoma expert from Weill Cornell Medicine in New York City.
Dr. Rutherford spoke to Patient Power co-founder Esther Schorr in a webinar last month.
“And now we have many more options than we did even just five years ago,” she said. “And I expect that five years from now, we'll have more and more, and that's really exciting for patients.”
Emerging DLBCL Treatments
Dr. Rutherford highlighted the latest findings on DLBCL treatments presented at the American Society of Clinical Oncology (ASCO) annual meeting, held May 29-31. During the virtual conference, she presented initial trial results of one novel targeted drug, venetoclax (Venclexta), in combination with a dose-adjusted chemoimmunotherapy (part chemotherapy, part immunotherapy) EPOCH-R, in treating aggressive B-Cell lymphomas.
Venclexta is approved to treat adult patients with chronic lymphocytic leukemia (CLL), as a combination treatment for patients aged 75 and older with previously untreated acute myeloid leukemia (AML), and has shown promise in treating multiple myeloma.
“We found that the particular dose of venetoclax, which is a BCL-2 inhibitor, on a schedule of five days along with chemotherapy was well-tolerated…,” Dr. Rutherford said. “BCL-2 is either rearranged or overexpressed in many of the aggressive B-Cell lymphomas and this drug, venetoclax, is a very promising agent to combine with chemotherapy in this patient population.”
Second-Line Therapy for Relapsed/Refractory DLBCL
While frontline therapy (such as rituximab [Rituxan] alone or in combination with chemotherapy) is curative in about two-thirds of patients if the disease comes back, patients typically get a second-line treatment, Dr. Rutherford said.
One second-line therapy that is showing promise is tafasitamab (MOR208), in combination with lenalidomide (Revlimid), which was granted priority review by the FDA in March. Tafasitamab is an antibody that targets a protein called CD19, which is present in high amounts on the surface of lymphoma cells. Phase II clinical trial data showed that 49% of patients experienced tumor reduction at a median time of 8.3 months, with 31% showing a complete response or no sign of cancer.
“Traditionally, the other monoclonal antibodies that we've used are targeted to CD20 (rituximab, for example), so this is a novel area for targeted treatment,” she said. “This combination is an emerging treatment option for people with relapsing refractory diffuse large B-Cell lymphoma.”
Dr. Rutherford is currently running a clinical trial with selinexor (Xpovio) in combination with chemoimmunotherapy for DLBCL patients. Xpovio was approved by the FDA as a treatment for patients with relapsed or refractory DLBCL last month. (It had already been approved in combination with dexamethasone for relapsed or refractory multiple myeloma.) Phase II trial results demonstrated a 29% overall response rate (ORR). Of those ORR successes, 13% had a complete response and 16% had partial responses.
“There have been some other exciting studies, and this is an emerging drug, which would be looking at this drug in a relapsed/refractory setting, so as a single agent,” she said. “And it's an oral drug, so that's appealing to many patients to not have to come in for an infusional treatment. That's something that I'll be looking at in the future as an option for these patients who desperately need more therapeutic treatment.”
Treating DLBCL with CAR T-Cell Therapy
CAR-T cells are also a new therapeutic option for patients for whom standard therapies have failed, said Dr. Joshua Brody, director of the Lymphoma Immunotherapy Program at Icahn School of Medicine at Mount Sinai in New York City. Dr. Brody participated in an April webinar on DLBCL treatments with Patient Power co-founder Andrew Schorr.
“The FDA has approved now two different versions (of CAR T-Cell therapy) for DLBCL, diffuse large B-Cell lymphoma, and a third one probably is going to be approved later this year,” he said. “And that's a very big deal. All of these new approvals we talk about are usually approved for patients for whom standard therapies have failed.”
He added: “…The one that will get FDA-approved this year, we have a hope, maybe not on day one when it gets approved, but over time we'll able to use it in the clinic and then patients won't have to get admitted to the hospital. That'll make it much easier to use and a more pleasant experience for patients we think with possibly fewer side effects.”
But for any of these new treatments to be effective, Dr. Rutherford said, there has to be an accurate diagnosis. That way treatment can be tailored to an individual patient's tumor characteristics.
“There are a number of exciting papers that have come out in the last couple of years that are really breaking diffuse large B-Cell lymphoma down into different categories that hopefully we'll be able to target specifically, and so that will improve the outcomes of those patients,” she said. “So, I think making sure that the pathologic assessment is done early is one of the most important parts.”
Watch the full interview and read the transcript: Emerging Treatments for Diffuse Large B-Cell Lymphoma.
- MorphosSys Therapy and Revlimid Eliminate Cancer in a Third of DLBCL Patients, Phase 2 Trial Shows
- Karyopharm’s Xpovio Wins Second FDA Approval for DLBCL Treatment
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