Therapy Combo Shows Promise in Tackling Lymphoma

Approximately 60% of patients diagnosed with diffuse large B-cell lymphoma—the most common type of lymphoma—can be cured with the current standard of care.

For patients whose cancer is resistant to these primary methods or whose cancer returns, options exist but present challenges. Effective alternative treatments are needed.

That’s why a new lymphoma therapy combination was tested at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, as part of a 15-site clinical trial of 120 patients in the U.S. and Canada.

“In reality, we don’t have a therapy to cure these patients or extend our patients’ lives despite all the new medications introduced and approved by the FDA,” said Izidore Lossos, M.D., chief of the Lymphoma Section in Sylvester’s Division of Hematology and professor of medicine at the Miller School

Dr. Lossos led the clinical site at Sylvester, where he is the endowed director of the lymphoma program, and co-authored an analysis of the study’s phase 1b and phase 2 in Nature Medicine.

“This trial tries to address how we can help patients who are not eligible for or failed stem cell transplant or CAR T therapy,” explained Dr. Lossos.

The Challenge of Large B-cell Lymphoma

One of the primary treatments for large B-cell lymphoma is R-CHOP, which consists of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone. If the patient does not respond to this therapy, an alternative is tried, such as chimeric antigen receptor (CAR) T-cell therapy or salvage treatment, followed by a stem cell transplant.

Therein lies the challenge.

Half of the patients are not eligible for a stem cell transplant, a procedure that removes the patient’s stem cells, treats them and then returns them to their body. And only half of those who undergo a stem cell transplant go into remission.

CAR T-cell therapy engineers the patient’s immune cells to fight the cancer, but some patients experience adverse effects and only about one-third have long-lasting, complete responses. Plus, the immunotherapy may not even be available, as patients must be treated in a specialized care facility.

Two Treatments Combined into One Therapy

To investigate an alternative for second-line therapy or beyond, researchers combined two treatments already in use independently. They gave patients mosunetuzumab, a bispecific antibody, with polatuzumab vedotin, an antibody-drug conjugate.

The bispecific antibody collects healthy immune system T cells along with lymphoma cells and binds them together to help the T cells find and fight the cancer cells. The antibody conjugate contains an antibody that targets the CD79b conjugate on the abnormal B-cell lymphocyte. Once bound together, the chemotherapeutic agent is released and taken up by the tumor cell, eventually killing it.

The trial treated 22 patients during phase 1b, which determined the best-tolerated dose over a 21-day cycle and between eight and 17 cycles of treatment.

In phase 2, 98 patients received the same combination treatment at the ideal dosage. Of these, nearly 60% responded to the therapy and nearly 46% went into remission. The combination of the two therapies showed more positive benefits compared with the complete response rates when the therapies were administered separately: 24% for mosunetuzumab and 13% for polatuzumab vedotin, respectively.

Furthermore, this combination treatment had a median progression-free survival of more than 11 months within the study’s follow-up of two years, which means the cancer went into remission or did not worsen during this period. The length of time is significant, considering most alternative treatments are less effective in abating this type of aggressive lymphoma.

The relatively low number of adverse events, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, from the combination supported outpatient use, according to the researchers.

What’s Next?

While not all patients’ cancers responded to the combo, Dr. Lossos personally observed the benefit of mosunetuzumab and polatuzumab vedotin in some patients whose cancers had not responded to other kinds of treatments.

“There are patients who are off therapy and doing well for two to three years,” he said.

Sylvester will continue as one of the treatment sites in the ongoing clinical trial. Dr. Lossos and other researchers leading the next phase of the study will compare the therapeutic combination with a standard chemotherapy.

Tags: diffuse large B cell lymphoma, Dr. Izidore Lossos, lymphoma, Sylvester Comprehensive Cancer Center