Therapy Combo Breakthrough for Lymphoma Treatment

The current standard of care can cure approximately 60% of individuals with diffuse large B-cell lymphoma, the most prevalent type of lymphoma.

Options exist but provide complications for people whose cancer is resistant to these principal techniques or whose cancer returns. Effective alternative treatments are required.

That is why, as part of a 15-site clinical trial involving 120 patients from the United States and Canada, a new lymphoma medication combination was examined at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

“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

R-CHOP, which combines rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone, is one of the principal therapies for large B-cell lymphoma. If this therapy does not work, another option is tried, such as chimeric antigen receptor (CAR) T-cell therapy or salvage treatment, followed by a stem cell transplant.
That is the difficulty.
Half of the patients are ineligible for a stem cell transplant, which involves removing the patient’s stem cells, treating them, and then returning them to their body. Only half of people who have a stem cell transplant achieve remission.

CAR T-cell treatment modifies the patient’s immune cells to fight cancer, but some patients endure side effects, and only around one-third of patients get long-term, full responses. Furthermore, because patients must be treated in a specialist care center, immunotherapy may not even be available.

Two Treatments Combined into One Therapy

Researchers combined two medicines that were already in use independently to study an alternative for second-line therapy or beyond. Patients were given mosunetuzumab, a bispecific antibody, in combination with polatuzumab vedotin, an antibody-drug conjugate.

The bispecific antibody gathers healthy immune system T cells as well as lymphoma cells and binds them together to assist T cells in locating and fighting cancer cells. An antibody in the antibody conjugate targets the CD79b conjugation on the aberrant B-cell lymphocyte. When the chemotherapeutic drug is bound together, it is released and taken up by the tumor cell, eventually destroying it.

During phase 1b, 22 individuals were treated to establish the best-tolerated dose across a 21-day cycle and between eight and 17 cycles of treatment.

98 patients in phase 2 received the same combo medication at the optimal dosage. roughly 60% of these patients responded to the medication, and roughly 46% went into remission. When the two medicines were delivered independently, the combination demonstrated more beneficial outcomes than the individual therapies: 24% for mosunetuzumab and 13% for polatuzumab vedotin, respectively.

Furthermore, throughout the study’s two-year follow-up, this combination treatment had a median progression-free survival of more than 11 months, indicating that the cancer went into remission or did not worsen during this time. Given that most alternative treatments are less effective in treating this type of aggressive lymphoma, the length of time is significant.

According to the researchers, the combination’s relatively low frequency of adverse events, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, warranted outpatient use.

What’s Next?

While not all patients’ tumors reacted to the combination, Dr. Lossos saw the advantage of mosunetuzumab and polatuzumab vedotin in certain individuals whose cancers had not responded to earlier treatments.

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

Sylvester will remain a treatment location in the ongoing clinical research. The next phase of the study, led by Dr. Lossos and other researchers, will compare the treatment combination to traditional chemotherapy.

Source: University of Miami Miller School of Medicine.