Commentary

Video

Dr Phillips on the Evaluation of Frontline Treatment With Acalabrutinib Plus BR in MCL

Tycel Phillips, MD, MPH, discusses the ongoing phase 3 ECHO trial of acalabrutinib plus bendamustine and rituximab in the front line for patients with mantle cell lymphoma.

Tycel Phillips, MD, MPH, associate clinical professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the ongoing phase 3 ECHO trial (NCT02972840) investigating the addition of acalabrutinib (Calquence) to bendamustine (Treanda) and rituximab (Rituxan; BR) in the frontline setting for patients with mantle cell lymphoma (MCL).

According to data presented at the 2023 ASCO Annual Meeting, updated findings from a phase 1b trial (NCT02717624) demonstrated that patients with previously untreated MCL achieved an overall response rate (ORR) of 94.4% with acalabrutinib plus BR, including a complete response (CR) rate of 77.8% at a median follow-up of 47.6 months. Moreover, 85.0% of patients with relapsed/refractory MCL experienced a response with the combination at a median follow-up of 20.4 months, including a 70% CR rate.

These data may provide support to the ongoing ECHO trial, Phillips says, which is evaluating the efficacy and safety of acalabrutinib and BR vs BR alone in treatment-naïve patients with MCL who are unfit or ineligible for autologous stem cell transplant (ASCT).

The readout of the ECHO data are highly anticipated, as they are expected to confirm the efficacy of acalabrutinib in earlier lines, Phillips states. Notably, results from this trial may potentially guide the use of acalabrutinib in different settings, Phillips emphasizes.

Should the ECHO trial yield positive results, this may lead to the exploration of frontline treatment with acalabrutinib in combination with venetoclax (Venclexta) and rituximab (Rituxan), Phillips says. The trial may also introduce an additional treatment option for patients who are ineligible for ASCT and secure access to acalabrutinib as a second-line treatment if it gains approval in that setting, he adds.

If the ECHO trial fails to meet its primary end point, access to acalabrutinib may become limited, Phillips continues. This would mirror what has been seen with ibrutinib (Imbruvica) in MCL following the data readout from the confirmatory phase 3 SHINE trial (NCT01776840), he suggests. The SHINE trial aimed to confirm the efficacy of ibrutinib in combination with bendamustine and rituximab in elderly, treatment-naïve patients with MCL. However, the regimen led to a higher incidence of adverse effects. As a result, the FDA retracted the indication for ibrutinib in MCL due to regulatory requirements linked to its accelerated approval status.

Ultimately, the outcome of the ECHO trial will help clarify the role of acalabrutinib and its optimal use in the MCL treatment arena, Phillips says. These results also have the potential to influence treatment strategies, ensuring that patients receive the most effective therapies tailored to their specific needs, Phillips concludes.

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