Martin Dreyling, MD, associate professor of medicine, University of Munich, head of the Lymphoma Program in the Department of Internal Medicine III, University Hospital of Munich (LMU), in Munich, Germany, discusses the key safety data from the phase 3 TRIANGLE trial (NCT02858258) in younger patients with mantle cell lymphoma (MCL).

Investigators evaluated the addition of ibrutinib (Imbruvica) to chemoimmunotherapy induction, followed by autologous stem cell transplant (ASCT) plus 2 years of ibrutinib maintenance vs chemoimmunotherapy and ASCT alone. A third arm also evaluated ibrutinib plus chemoimmunotherapy induction without ASCT, followed by ibrutinib maintenance. Induction therapy consisted of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin).

Data from the study presented at the 2022 ASH Annual Meeting

 showed that the 3-year failure-free survival rate (FFS) was 72% with standard induction and ASCT alone compared with 88% for ibrutinib plus induction, ASCT, and ibrutinib maintenance (HR, 0.52; 

Additionally, standard chemoimmunotherapy induction and ASCT failed to show superior FFS vs ibrutinib plus chemoimmunotherapy induction and 2-years of ibrutinib maintenance without ASCT. The 3-year failure-free survival rate was 72% for chemoimmunotherapy/ASCT vs 86% with ibrutinib without ASCT (HR, 1.77; 

Because FFS and overall survival outcomes overlapped on the curves for the 2 experimental ibrutinib arms, evaluating safety was key to distinguish between the two regimens, Dreyling explains. Investigators found that the addition of ASCT to ibrutinib/chemoimmunotherapy induction and ibrutinib maintenance significantly increased toxicity, primarily for hematological adverse effects and also infections, Dreyling adds. Notably, safety data for ibrutinib induction and maintenance without ASCT was comparable to chemoimmunotherapy induction and ASCT alone, without the acute toxicity of transplantation, Dreyling continues.

Of the 3 treatment arms, the standard treatment with chemoimmunotherapy induction and ASCT alone was outperformed by both ibrutinib-containing arms, Dreyling says. Although investigators are still waiting for additional data to differentiate the 2 experimental arms, toxicity favors the ibrutinib arm without ASCT, which would represent a major shift in standard of care, Dreyling concludes.

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Martin Dreyling, MD, discusses the key safety data from the phase 3 TRIANGLE trial in younger patients with mantle cell lymphoma. 

Dr. Dreyling on Key Safety Data from the TRIANGLE Trial in MCL

Martin Dreyling, MD, associate professor of medicine, University of Munich, head of the Lymphoma Program in the Department of Internal Medicine III, University Hospital of Munich (LMU), Germany, discusses key efficacy results from the phase 3 TRIANGLE study (NCT02858258) in mantle cell lymphoma (MCL).

The open-label trial evaluated the addition of ibrutinib (Imbruvica) to standard induction chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) and fixed 2-year maintenance for young patients with mantle cell lymphoma. Induction therapy consisted of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone)/R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin).

Patients were randomly assigned to 1 of 3 treatment arms including induction/maintenance ibrutinib plus induction chemoimmunotherapy with ASCT and, ibrutinib plus induction chemoimmunotherapy and maintenance ibrutinib without ASCT, or a standard arm of induction therapy and ASCT alone.

A head-to-head comparison of all treatment arms showed a 3-year failure-free survival (FFS) rate of 72% in the standard arm, 86% in the ibrutinib without ASCT arm, and 88% in the ibrutinib with ASCT arm, Dreyling states. Although overall survival (OS) data are not fully mature, the 3-year OS rates showed that patients receiving the ibrutinib induction/maintenance experience improved outcomes compared to patients receiving standard ASCT alone.

Moreover, investigators originally postulated that ASCT would retain its status as the current standard of care if it demonstrated superiority over ibrutinib, Dreyling continues. However, ibrutinib-containing arms demonstrated improved FFS, clinically meaningful benefit, and OS benefit regardless of whether ASCT was administered, he says. 

Although no verdict on the role of ASCT has been reached, the ibrutinib without ASCT regimen was also associated with decreased toxicity, implying that ASCT may no longer be considered a standard treatment component for this patient population.

Martin Dreyling, MD, discusses key efficacy results from the phase 3 TRIANGLE study in mantle cell lymphoma.

Dr. Dreyling on Key Efficacy Results From the TRIANGLE Study in MCL

Martin Dreyling, MD, professor of medicine, University of Munich Hospital in Grosshadern, discusses primary results of the pivotal CHRONOS-1 study, which looked at copanlisib in patients with relapsed or refractory indolent B-cell lymphoma, during the AACR Annual Meeting.

Although there are treatments options currently available for these patients, all of the 142 patients included in the study had already undergone at least 2 prior lines of therapy, with the majority of the patients being refractory to the previous approaches.

Surprisingly, these patients still responded to the PI3K inhibitor copanlisib, Dreyling says. In fact, there was almost a 60% response rate demonstrated in the study. In marginal zone lymphoma, the response rate was almost 70%, and the duration of the response was 22 months, Dreyling explains.

With regard to toxicity, Dreyling adds there was no major colitis observed, and elevated liver enzymes have rarely been observed.

Martin Dreyling, MD, associate professor, University of Munich, discusses primary results of the pivotal CHRONOS-1 study, which looked at copanlisib in patients with relapsed or refractory indolent B-cell lymphoma, during the AACR Annual Meeting.

Martin Dreyling, MD

Articles

Dr. Dreyling on Key Safety Data from the TRIANGLE Trial in MCL

Dr. Dreyling on Key Efficacy Results From the TRIANGLE Study in MCL

Dr. Dreyling on Results for Copanlisib in Patients With B-Cell Lymphoma