Carlo Visco, MD, an associate professor within the Department of Medicine and Section of Hematology at the University of Verona, in Verona, Italy, discusses the results of early relapse versus late relapse in the MANTLE-FIRST study with ibrutinib (Imbruvica)versus chemoimmunotherapy in mantle cell lymphoma (MCL).

In the MANTLE-FIRST study, investigators evaluated outcomes in patients with MCL who were in first relapse following up-front treatment with high-dose cytarabine and standard regimens. Patients were divided into those who are early-progressors (POD), or those who were refractory to standard induction, and those who relapsed or progressed within 2 years from their lymphoma diagnosis, says Visco. 

The 2 cohorts consisted of patients with early POD and those who relapse later on and up to 2 years. These 2 populations are very different in terms of survival, according to Visco. Those with early relapse disease typically have a median overall survival (OS) around 2 years from the time of relapse while those with late relapse disease have a life expectancy that is much longer, of around 5 years or more, Visco adds.

It is important to remember that those with early-relapse disease have an unmet need. The main takeaway from the MANTLE-FIRST trial was that when patients were divided between early or late relapse, ibrutinib was favorable compared with standard chemoimmunotherapy in terms of survival, according to Visco. This approach conferred a progression-free survival and OS advantage when given in the second-line setting, concludes Visco.

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Carlo Visco, MD, discusses the results of early relapse versus late relapse in the MANTLE-FIRST study with ibrutinib versus chemoimmunotherapy in mantle cell lymphoma.

Dr. Visco on Results from the MANTLE-FIRST Study in Relapsed/Refractory MCL

Carlo Visco, MD, an associate professor within the Department of Medicine and Section of Hematology at the University of Verona, in Verona, Italy, discusses the next steps for the international, retrospective MANTLE-FIRST trial in patients with relapsed/refractory mantle cell lymphoma (MCL).

In the MANTLE-FIRST trial, investigators evaluated the outcomes of younger patients with MCL who had progressive disease or first relapse following treatment with high-dose cytarabine and autologous stem cell transplantation. Two next steps should be explored with this study, says Visco. 

The first step is biological; the field needs to understand why these patients fare worse than others and why some relapse early when they are treated with drugs such as ibrutinib (Imbruvica), cytarabine, or rituximab (Rituxan), says Visco. Additionally, the biology of tumors that harbor 

 mutations must be analyzed; this means utilizing more gene sequencing to determine mutational status, explains Visco.

The Italian Lymphoma Foundation (FIL) has sponsored another trial, which will investigate these biological factors further, says Visco. The second step will be to examine patients who relapse later on. A study like that will take place next year in Europe. The follow-up of these patients will be longer and yield more mature data that can be analyzed to see what happens in the later-line setting, concludes Visco.

Carlo Visco, MD, discusses the next steps for the international, retrospective MANTLE-FIRST trial in patients with relapsed/refractory mantle cell lymphoma.

Dr. Visco on Next Steps for the MANTLE-FIRST Trial in Relapsed/Refractory MCL

Carlo Visco, MD, associate professor, Department of Medicine, Section of Hematology, University of Verona, Verona, Italy, discusses the utility of bendamustine-based regimens in mantle cell lymphoma (MCL).

The BTK inhibitor ibrutinib (Imbruvica) has established a role as standard treatment for patients with MCL who have received at least 1 prior line of therapy, explains Visco.

However, in some cases, patients may not be eligible to receive ibrutinib, Visco says. In these instances, chemotherapy-based regimens are often utilized.

Bendamustine-based regimens, such as bendamustine plus rituximab (Rituxan; BR) or BR plus cytarabine (R-BAC), should be considered standard for these patients, says Visco. 

Moreover, bendamustine-based therapies have demonstrated significantly superior rates of progression-free survival and overall survival compared with other chemotherapy regimens, concludes Visco.

Carlo Visco, MD, discusses the utility of bendamustine-based regimens in mantle cell lymphoma.   



Dr. Visco on the Utility of Bendamustine in MCL 

Carlo Visco, MD, associate professor, Department of Medicine, Section of Hematology, University of Verona, Verona, Italy, discusses the utility of cytarabine in relapsed/refractory mantle cell lymphoma (MCL).

As demonstrated in past studies, younger patients with MCL should receive higher doses of cytarabine during induction therapy to obtain optimal results, says Visco. ​Notably, cytarabine-based regimens have become a standard in the space. 

Conversely, elderly patients cannot tolerate high doses of this agent​, Visco explains.

As such, future research efforts should aim to identify additional first-line treatment regimens for ​older patients with MCL, Visco concludes. 

Carlo Visco, MD, discusses the utility of cytarabine in relapsed/refractory mantle cell lymphoma. 

Dr. Visco on the Utility of Cytarabine in MCL 

Carlo Visco, MD, associate professor, Department of Medicine, Section of Hematology, University of Verona, Verona, Italy, discusses the rationale for the international, retrospective MANTLE-FIRST trial in relapsed/refractory mantle cell lymphoma (MCL).

The MANTLE-FIRST trial evaluated the outcomes of patients with MCL who had progressive disease or first relapse following treatment with high-dose cytarabine (HDAC) and autologous stem cell transplantation in eligible patients.

Although MCL remains a difficult-to-treat disease, the up-front treatment of patients is well established, Visco explains.

However, the second-line setting of MCL does not have a well-defined standard of care, and the majority of patients with MCL who go into remission will eventually relapse, says Visco. As such, establishing a standard of care regimen for patients who fail induction therapy remains an unmet need, Visco concludes.

Carlo Visco, MD, discusses the rationale for the international, retrospective MANTLE-FIRST trial in relapsed/refractory mantle cell lymphoma.  

Carlo Visco, MD

Articles

Dr. Visco on Results from the MANTLE-FIRST Study in Relapsed/Refractory MCL

Dr. Visco on Next Steps for the MANTLE-FIRST Trial in Relapsed/Refractory MCL

Dr. Visco on the Utility of Bendamustine in MCL

Dr. Visco on the Utility of Cytarabine in MCL

Dr. Visco on the Rationale for the MANTLE-FIRST Trial in R/R MCL