Simon Rule, MD, professor of hematology, University of Plymouth, discusses the next steps for ibrutinib (Imbruvica) and other BTK inhibitors in the treatment landscape of mantle cell lymphoma (MCL).

At the 2019 ASH Annual Meeting, 7.5-year follow-up data from a pooled analysis showed that ibrutinib led to more favorable responses versus chemotherapy in patients with relapsed/refractory MCL. There are also data with the combination of ibrutinib and venetoclax (Venclexta) in the relapsed/refractory setting.

The data that Rule presented at the meeting showed that ibrutinib led to high response rates in asymptomatic patients. As such, Rule believes the next step will be to move ibrutinib and other BTK inhibitors into earlier lines of treatment.

Several trials are evaluating the use of ibrutinib in the frontline setting. One such trial in the United Kingdom is evaluating the combination of ibrutinib and rituximab (Rituxan) versus chemotherapy in older patients. Moreover, an ongoing trial is evaluating ibrutinib plus venetoclax and obinutuzumab (Gazyva). To date, 14 out of 15 patients had minimal residual disease—negative complete remissions. With further study, chemotherapy may not be necessary in the up-front setting, concludes Rule.

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Dr. Rule on the Next Steps for BTK Inhibitors in MCL

Simon Rule, MD, professor of hematology, University of Plymouth, discusses long-term follow-up data from a pooled analysis of ibrutinib (Imbruvica) monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL).

Dr. Rule on Long-Term Follow-Up of Ibrutinib Monotherapy in Relapsed/Refractory MCL

Simon Rule, MD, professor of hematology, University of Plymouth, discusses the potential for CAR T-cell therapy in treating patients with mantle cell lymphoma (MCL).

Data on using CAR T-cell therapy to treat patients with MCL will be presented at the 2019 ASH Annual Meeting. Rule is hoping CAR T-cell therapy will be a contributing treatment and believes it will work best post-BTK inhibitor.

CAR T-cell therapy may even have the potential to replace allogeneic stem cell transplant, according to Rule. This would be a positive advance because many physicians do not like the toxicity associated with allogeneic stem cell transplant, particularly graft-versus-host disease. However, long-term data are necessary before CAR T-cell therapy is used in place of allogeneic stem cell transplant, concludes Rule.

Simon Rule, MD, discusses the potential for CAR T-cell therapy in treating patients with mantle cell lymphoma.

Dr. Rule on Potential for CAR T-Cell Therapy in MCL

Simon Rule, MD, professor of hematology, University of Plymouth, discusses the future therapeutic landscape of mantle cell lymphoma (MCL).

Recognition of high-dose cytarabine and the addition of rituximab (Rituxan) to chemotherapy as staples of treatment have been 2 of the main advances made in MCL, says Rule. Learning that rituximab can be of benefit in the maintenance setting was another key development.

However, with the advent of BTK inhibitors, the field is going to become less reliant on chemotherapy, he says. Several trials are evaluating chemotherapy-free regimens. Notably, a trial in the United Kingdom is evaluating the combination of rituximab and ibrutinib (Imbruvica) in comparison with rituximab and chemotherapy in this patient population. The trial will determine whether frontline chemotherapy is necessary in an elderly patient population, explains Rule.

Ibrutinib has shown high responses as a single agent, so the next logical step will be to evaluate the agent in combination with other potent drugs, such as venetoclax (Venclexta). Minimal residual disease may also come into play after induction to determine whether additional therapy is warranted or whether treatment can be discontinued, concludes Rule. 

Simon Rule, MD, professor of hematology, University of Plymouth, discusses the future therapeutic landscape of mantle cell lymphoma.

Dr. Rule on the Future Therapeutic Landscape of MCL

Simon Rule, MD, professor of hematology, University of Plymouth, discusses a study comparing patients with newly diagnosed mantle cell lymphoma (MCL) who receive immediate systemic treatment versus patients who are closely monitored instead.

A registry has been collecting information, such as disease, blood, marrow, and germline DNA from almost 600 patients with newly diagnosed MCL. There are no exclusion criteria, allowing this biobank to capture information from all patients.

Within that study, Rule and researchers are suggesting if patients are asymptomatic with low-volume disease, it is better to hold off on administering treatment and monitor instead. There is a prospective study comparing patients who are waiting and patients who require treatment immediately to see if researchers can bind a biomarker indicating indolent disease, which is defined as going untreated for 2 years.

Simon Rule, MD, discusses a study comparing patients with newly diagnosed mantle cell lymphoma who receive immediate systemic treatment immediately versus patients who are closely monitored instead.

Simon Rule, MD

Articles

Dr. Rule on the Next Steps for BTK Inhibitors in MCL

Dr. Rule on Long-Term Follow-Up of Ibrutinib Monotherapy in Relapsed/Refractory MCL

Dr. Rule on Potential for CAR T-Cell Therapy in MCL

Dr. Rule on the Future Therapeutic Landscape of MCL

Dr. Rule on Searching for a Biomarker Indicating Indolent MCL