Published on July 26, 2021
Non-Hodgkin Lymphoma News From ASCO 2021
New treatment options are emerging for patients with non-Hodgkin lymphoma (NHL). Researchers discussed two of these therapies at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, held online on June 4-8. Both are combination therapies that include polatuzumab vedotin-piiq (Polivy) — a type of drug that delivers targeted doses of chemotherapy to cancer cells — and both are showing promise in patients with difficult-to-treat disease.
The U.S. Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin-piiq in 2019. It was approved for use in combination with the chemotherapy drug bendamustine (Bendeka and Treanda) and rituximab products to treat adult patients with diffuse large B-cell lymphoma (DLBCL) whose disease has progressed or returned after at least two prior therapies. DLBCL is the most common form of NHL and affects B cells, a type of white blood cell.
Polatuzumab vedotin-piiq is an antibody-drug conjugate (ADC). It consists of a chemotherapy drug attached to an antibody that binds to a protein called CD79b, which is found only on B cells. The B cells absorb the polatuzumab vedotin-piiq, allowing it to deliver the chemotherapy drug directly into the cell. This spares cells in the body other than B cells from the toxicity of the chemotherapy.
Researchers are exploring the use of polatuzumab vedotin-piiq in combination with a variety of other treatments.
A Different Triple Combination Therapy
Polatuzumab vedotin-piiq is currently approved in combination with rituximab and bendamustine, but researchers are testing whether it could be added to rituximab and lenalidomide (Revlimid), a drug combination that has been approved for a variety of other blood cancer types. During a clinical trial, researchers evaluated the safety and efficacy of this novel combination of three drugs for patients with relapsed (the cancer has returned) or refractory (the cancer has stopped responding to treatment) DLBCL.
“In this first report of the triplet combination of polatuzumab, rituximab, and lenalidomide, the triplet combination showed notable efficacy in a challenging-to-treat relapsed and refractory diffuse large B-cell lymphoma population,” lead study author Catherine S. Magid Diefenbach, MD, said when presenting the results. Dr. Diefenbach is the director of the Clinical Lymphoma Program at NYU Langone Health’s Perlmutter Cancer Center in New York.
The overall response rate was 39% in the group of patients who took the combination to test its effectiveness. This means that more than a third of patients had their cancers shrink or disappear after starting the treatment. Among all the patients, 29% had a complete response, meaning the cancer disappeared. Most of the patients who experienced a complete remission still had no known cancer remaining at the end of the study.
Three-quarters of the patients in the group that took the combination to test its safety experienced severe or life-threatening side effects. The most common severe or life-threatening side effects reported during the study were neutropenia (low white blood cell levels), thrombocytopenia (low platelet levels), and infections.
Adding an Investigational Drug
In another trial, researchers evaluated the safety and efficacy of polatuzumab vedotin-piiq in combination with mosunetuzumab to treat relapsed or refractory B-cell NHL. Mosunetuzumab is a bispecific antibody that targets CD3 on the surface of T cells and CD20 on the surface of B cells, recruiting the T cells to attack and kill the B cells. Mosunetuzumab is being investigated alone and in combination with various other drugs, but it has not been approved by the FDA.
Lead study author Elizabeth Budde, MD, PhD, presented results from an early study during the ASCO meeting. Dr. Budde is a hematologist-oncologist at City of Hope Comprehensive Cancer Center in Duarte, California.
Mosunetuzumab with polatuzumab vedotin-piiq “shows promising efficacy in patients with relapsed/refractory NHL with predominately aggressive histology,” Dr. Budde said. “Complete response rate was seen in 54.5% [of patients].”
All patients reported experiencing at least one side effect, with neutropenia, nausea, fatigue, and diarrhea being the most common. However, Dr. Budde pointed out that no one participating in the trial experienced neurotoxicity, nor moderate-to-severe cytokine release syndrome, a potentially dangerous inflammatory immune response often characterized by fever, nausea, headache, and heartbeat and blood pressure changes. These side effects have been seen with other bispecific antibodies.
“This analysis of the phase 1b portion of the study demonstrated that [mosunetuzumab with polatuzumab vedotin-piiq] has an acceptable safety profile,” Dr. Budde said at the end of her presentation.
Further research is needed for both novel combination therapies outlined above.
To learn more about NHL, visit What is Non-Hodgkin Lymphoma? For questions about either of the therapies listed above, please speak to a lymphoma specialist.
See Our Sources
- Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial.
- FDA approves first chemoimmunotherapy regimen for patients with relapsed or refractory diffuse large B-cell lymphoma.
- Promising tolerability and efficacy results from dose-escalation in an ongoing phase Ib/II study of mosunetuzumab (M) with polatuzumab vedotin (Pola) in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin’s lymphoma (B-NHL).
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