David Ritchie, MD, PhD, hematologist, head of allogenic stem cell transplantation, Peter MacCallum Cancer Centre, discusses immunological recovery with venetoclax (Venclexta) and ibrutinib (Imbruvica) in mantle cell lymphoma (MCL).

The important take-home message from an immunological analysis in the phase II AIM study (NCT02471391) was that the responses to the combination took time to evolve. When the immunological status was analyzed at diagnosis or inclusion in the study, researchers looked at results 16 weeks later and saw no improvement in immunological status. However, there was complete normalization of the immunological status at 1 year posttreatment, which was sustained for 2 years posttreatment, says Ritchie.

This is important because, initially, exposure to venetoclax and ibrutinib can be associated with immunological impairment. However, the subsequent normalization and improvement in immune status likely reflects the lower rates of opportunistic infections that those patients saw on the clinical trial. It also reflects the potential for those patients to be treated with subsequent immunotherapy. Investigators of the trial felt that the findings were uniform across the group and associated with sustained responses, concludes Ritchie.

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David Ritchie, MD, PhD, discusses immunological recovery with venetoclax (Venclexta) and ibrutinib (Imbruvica) in mantle cell lymphoma.

Dr. Ritchie on Immunological Recovery With Venetoclax and Ibrutinib in MCL

David Ritchie, MD, PhD, hematologist, head of allogenic stem cell transplantation, Peter MacCallum Cancer Centre, discusses the rationale of the AIM trial in relapse/refractory mantle cell lymphoma (MCL).

The patient population of the phase II AIM trial (NCT02471391) comprises those who either failed to respond to initial chemotherapy or had short remissions after treatment. Many of these patients had gone through intensive chemotherapy, including autologous stem cell transplantation. These are patients who had no other therapeutic options, said Ritchie.

The primary driver of the study was to explore the safety and efficacy of the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta). It is important to have comprehensive biomarker specimens as a part of the study, which allows researchers to look at this immunological reconstitution, as well as look for those biomarkers in the compliment species, concludes Ritchie.

David Ritchie, MD, PhD, discusses the rationale of the AIM trial in relapsed/refractory mantle cell lymphoma (MCL).
 

Dr. Ritchie on the Rationale of the AIM Trial in Relapsed/Refractory MCL

David Ritchie, MD, PhD, hematologist, head of allogenic stem cell transplantation, Peter MacCallum Cancer Centre, discusses the immunologic impact of long-term venetoclax (Venclexta) and ibrutinib (Imbruvica) in relapsed/refractory mantle cell lymphoma (MCL).

The phase II AIM trial (NCT02471391) evaluated ibrutinib and venetoclax in patients with relapsed/refractory MCL. At 16 weeks, the overall response rate was 71%. Of 24 patients treated, 16 remained on the combination for more than 1 year.

A subset analysis presented at the 2019 ASH Annual Meeting confirmed that long-term treatment with the combination is associated with immune recovery, as well as changes in inflammatory biomarkers. The majority of patients showed normalization in their immune status, says Ritchie.

As such, it is hypothesized that if normalization occurs within a year of starting treatment with venetoclax/ibrutinib, the antitumor response could be sustained beyond that. Moreover, patients with a normalized immune system may respond better to subsequent therapy upon disease progression, concludes Ritchie.

David Ritchie, MD, PhD, discusses the immunologic impact of long-term venetoclax and ibrutinib in relapsed/refractory mantle cell lymphoma.

Dr. Ritchie on the Immunologic Impact of Long-Term Venetoclax/Ibrutinib in R/R MCL

David Ritchie, MD, PhD, hematologist, head of allogenic stem cell transplantation, Peter MacCallum Cancer Centre, discusses the long-term immunological response to the combination of venetoclax (Venclexta) and ibrutinib (Imbruvica) in relapsed/refractory mantle cell lymphoma (MCL).

Based on data from the phase II AIM study (NCT02471391), the combination of venetoclax and ibrutinib demonstrated encouraging efficacy and a 71% overall response rate in patients with relapsed/refractory disease.

A subset analysis looked at the longitudinal changes in peripheral blood immunology to determine if disease control is associated with normalization of immune responses in these patients, says Ritchie.

The analysis showed that long-term treatment with venetoclax and ibrutinib is associated with immune recovery in patients with relapsed/refractory MCL, explains Ritchie. The majority of patients showed normalization of their immune status and improvement in innate immunity cells. Additionally, changes in inflammatory biomarker expression were noted in patients treated with the combination.

Patients showed biological improvement in monocytes, dendritic cells, gamma delta T cells, and natural killer cells, says Ritchie.

The analysis suggests that venetoclax and ibrutinib may provide immunological recovery over conventional chemotherapy.

David Ritchie, MD, PhD, discusses the long-term immunological response to the combination of venetoclax and ibrutinib in relapsed/refractory mantle cell lymphoma.



David Ritchie, MD, PhD

Articles

Dr. Ritchie on Immunological Recovery With Venetoclax and Ibrutinib in MCL

Dr. Ritchie on the Rationale of the AIM Trial in Relapsed/Refractory MCL

Dr. Ritchie on the Immunologic Impact of Long-Term Venetoclax/Ibrutinib in R/R MCL

Dr. Ritchie on Immunological Response to Venetoclax/Ibrutinib in R/R MCL