Drug Combination Improves Outcomes for Common Type of Lymphoma

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Mary Ann Cornell stands behind the wheel of a boat.

Since retiring from teaching, Mary Ann Cornell has spent as much time as she can on the water.

Mary Ann Cornell was active and otherwise healthy when she received a diagnosis of diffuse large B cell lymphoma (DLBCL) at age 80, in the fall of 2019. When she learned she had this blood cancer, the most common type of non-Hodgkin lymphoma, the native New Yorker and retired teacher sought out treatment at Memorial Sloan Kettering Cancer Center.

At her first appointment with MSK medical oncologist Matthew Matasar, Mary Ann found out that she qualified for a clinical trial looking at a drug called polatuzumab vedotin (PolivyTM, often called pola for short). The drug had previously received approval from the US Food and Drug Administration for treating DLBCL that returns after standard treatment. It was now being tested in patients who were newly diagnosed, like Mary Ann.

“I told him I was happy to participate,” says Mary Ann, now 83. “I’m very grateful that I did. It gave me a new lease on life.”

The trial that Mary Ann was a part of, known as the POLARIX study, was presented on December 14, 2021, at the American Society of Hematology (ASH) annual meeting. The researchers reported that the number of patients who remained cancer-free after two years increased from about 70% for those who received standard therapy to nearly 77% for those who had pola added to their treatment. The trial results are also published in the New England Journal of Medicine (NEJM). The senior author of the NEJM paper is Gilles Salles, Chief of the Lymphoma Service in MSK’s Division of Hematologic Malignancies, who presented the findings at the ASH meeting media event. Dr. Matasar is also an author of the paper.

Looking for Better Treatments

Almost 30,000 cases of DLBCL are diagnosed in the United States every year. The current standard therapy is known as R-CHOP, an acronym for its mix of drugs. The R-CHOP combination, which was established in the early 2000s, cures about two-thirds of patients. For the rest, better treatments are needed.

“Over the past two decades, there have been many attempts to improve R-CHOP by modifying the doses or adding new drugs,” says Dr. Salles, who developed the POLARIX trial while working in France, before he joined MSK. “Unfortunately, these efforts have been unsuccessful. Therefore, there’s been a great unmet need for new ways to treat this potentially curable disease.”

Polatuzumab vedotin is a type of drug known as an antibody-drug conjugate. It’s made up of two parts: an antibody that homes in specifically on the cancer cells and a chemotherapy drug called monomethyl auristatin E. When the antibody finds and enters the cancer cell, it brings along the chemotherapy, which destroys the cancer cell. In the experimental arm of the trial, pola replaces one of the drugs in the R-CHOP regimen.

There's been a great unmet need for new ways to treat this potentially curable disease.
Gilles Salles Lymphoma Service Chief

The new study, which included 879 patients from all over the world, was a phase 3 trial, with half of the patients receiving standard treatment and half receiving the updated combination with pola. Because the trial was blinded, both Dr. Matasar and Mary Ann don’t know which treatment she got. What they do know is that she’s doing well: Her scans and blood tests show no evidence of cancer.

“Participating in this kind of trial gives a patient the chance of receiving medicine that may be better, and they’re guaranteed to at least receive the best current standard of care,” says Dr. Matasar. He is very familiar with the drug — he led the trial that resulted in polatuzumab vedotin’s earlier approval for advanced disease in 2019.

“From the patient’s perspective, it’s a win-win situation,” he adds. “But agreeing to enroll in a trial is also an act of generosity that has great potential to benefit others in the future.”

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‘Like a Miracle’

Mary Ann learned about MSK’s expertise in treating lymphoma after making a call to MSK Direct when she first received her diagnosis. MSK Direct provides its business and union partners with guided access to MSK’s experts, services, and support for their employees or members. Mary Ann was able to access these services because she’s a retired New York City public school teacher with benefits from the United Federation of Teachers Welfare Fund.

Agreeing to enroll in a trial is also an act of generosity that has great potential to benefit others in the future.
Matthew J. Matasar hematologic oncologist

Mary Ann normally spends her winters in Florida, but when she was diagnosed with DLBCL at the end of 2019, she returned to her home in Lake Ronkonkoma on Long Island so that she could receive care at MSK.

The main side effect that Mary Ann experienced in the trial was peripheral neuropathy — numbness and tingling in her hands and feet. This was one of the most common side effects in the trial overall, along with neutropenia and anemia (reduced numbers of white and red blood cells, respectively). The side effects were similar for both groups of patients on the trial.

As an avid sailor and swimmer who loves spending time near the water, Mary Ann was concerned about the neuropathy. She completed several weeks of occupational and physical therapy at MSK and then continued that therapy when she returned to her second home in Florida. Today, she still has some aftereffects from the treatment, but is feeling much better.

This coming January, Mary Ann plans to marry her partner of 13 years, Dan, who is also 83. She feels very grateful for the support that Dan provided throughout her chemo, as well as for the help and encouragement from her siblings, Dan’s family, and many close friends.

“I’m very happy that I feel strong and independent again,” she says. “It feels like a miracle.”

 

Key Takeaways
  • Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and is diagnosed in almost 30,000 people in the United States every year.
  • Because the current standard treatment, a mixture of drugs known as R-CHOP, cures about two-thirds of patients, better treatments are needed.
  • A phase 3 trial has found that replacing one of the drugs in R-CHOP with a newer drug called polatuzumab vedotin improves outcomes for patients.
  • The side effects for the two drug combinations were about the same.
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The POLARIX trial was funded by Genentech Inc. and F. Hoffmann-LaRoche, the companies that make polatuzumab vedotin, and conducted in collaboration with the Lymphoma Study Association and the Lymphoma Academic Research Association.

Dr. Salles and Dr. Matasar have both received funding and honoraria from these companies. Dr. Salles also has received financial compensation for participating in advisory boards, educational events, and overall consulting from Abbvie, Bayer, Beigene, BMS/Celgene, Epizyme, Genmab, Gilead/Kite, Incyte, Ipsen, Loxo, Milteniy, Morphosys, Novartis, Rapt, Regeneron, and Takeda. Dr. Matasar also has relationships with or financial interests in Bayer, Daiichi Sankyo, GlaxoSmithKline, Immunovaccine Technologies Inc., Janssen Pharmaceuticals Inc., Merck & Co. Inc., Monsanto, Pharmacyclics, Rocket Pharmaceuticals, Seattle Genetics, Takeda Pharmaceuticals, and Teva Pharmaceutical Industries Ltd.