Acalabrutinib (Calquence) plus bendamustine and rituximab (Rituxan; BR) continued to improve progression-free survival (PFS) vs placebo plus BR after an additional year of follow-up in patients with previously untreated mantle cell lymphoma (MCL), according to updated data from the phase 3 ECHO trial (NCT02972840) presented at the
At a median follow-up of 60.8 months (range, 0-88.5), patients who received acalabrutinib plus BR (n = 299) experienced a median PFS of 72.5 months (95% CI, 60.7-not evaluable [NE]) compared with 47.8 months (95% CI, 36.1-60.8) for those who received placebo plus BR (n = 299), resulting in a PFS risk reduction of 32% (HR, 0.68; 95% CI, 0.53-0.87; log-rank P = .0022).
“These results emphasize the benefits of acalabrutinib plus BR as a first-line treatment approach, improving PFS and delaying the need for subsequent therapies in patients with treatment-naive MCL,” said lead study author Michael L. Wang, MD, and coauthors in a presentation of the data. “Collectively, our data demonstrated that concurrent acalabrutinib plus BR as triple frontline therapy is preferable to sequential therapy with BR followed by a BTK [Bruton tyrosine kinase] inhibitor.”
The randomized, double-blind, and multicenter trial enrolled patients who were 65 years old and older with an ECOG performance status of 2 or less. Patients needed to have pathologically confirmed MCL and have received no prior systemic anticancer therapy.2
If patients had significant cardiovascular disease, malabsorption syndrome, disease significantly affecting gastrointestinal function, or uncontrolled active systemic infections, they were not included in the trial.
Patients were randomly assigned to each arm, with both arms receiving bendamustine plus rituximab for six 28-day cycles.1 If patients in either arm experienced a partial response or better, they received maintenance rituximab. Patients in the acalabrutinib arm received twice-daily 100 mg oral doses of acalabrutinib until they experienced progressive disease (PD) or toxicity. In the placebo arm, patients also received twice-daily placebo doses until PD or toxicity, although crossover to acalabrutinib was permitted following disease progression. If patients in either arm experienced a partial response or better, they received maintenance rituximab for 2 years.
The primary end point was independent review committee–assessed PFS, with independent review committee-assessed overall response rate, overall survival (OS), and safety as key secondary end points.
Updated data revealed that 33 patients in the acalabrutinib arm received at least 1 subsequent line of anticancer therapy vs 100 patients in the placebo arm. In the acalabrutinib arm, 12, 11, 9, and 1 patient received BTK inhibitors, chemotherapy, non-BTK inhibitor targeted therapies, or other therapies as their second-line treatment. In the placebo arm, 79 patients received BTK inhibitors as second-line treatment, 13 received chemotherapy, 6 received non-BTK inhibitor targeted therapy, and 3 received other therapies. Ten patients in the acalabrutinib arm went on to receive third-line anticancer therapy, with 3 receiving fourth-line therapy. In the placebo arm, 37 patients received third-line therapy and 14 received fourth-line therapy.
At a median follow-up of 51.9 months (range, 0.03-93.04), patients in the acalabrutinib arm demonstrated a median OS that was NE (95% CI, 73.3-NE) vs NE (95% CI, 73.8-NE) in the placebo arm (HR, 0.87; 95% CI, 0.67-1.13). Median OS rates, censored for COVID-19 deaths, were also NE (95% CI, NE-NE) in the acalabrutinib arm and NE (95% CI, 85-NE) in the placebo arm (HR, 0.78; 95% CI, 0.57-1.06).
The median time to third-line treatment was 10 months for the acalabrutinib arm vs 37 months for the placebo arm (HR, 0.76; 95% CI, 0.59-0.98; log-rank P = .0341). At 48 months, 67.6% of patients in the acalabrutinib arm had not yet initiated third-line therapy or died, compared with 59.2% in the placebo arm.
Investigators noted that the safety profile of acalabrutinib plus BR remained favorable and similar to placebo plus BR despite continuous acalabrutinib exposure, with no new signals identified at the longer follow-up.
Among safety-evaluable patients in the acalabrutinib arm (n = 297), grade 3 or higher adverse events (AEs) occurred in 89.2% vs 88.6% in the placebo arm (n = 297). Any grade AEs occurred at rates of 99.7% and 99% of the acalabrutinib and placebo arms, respectively.
One new case of grade 3 or higher atrial fibrillation was reported in the acalabrutinib arm, and 1 additional case of any-grade ventricular tachyarrhythmia was found in the placebo arm. Total grade 3 or higher cardiac events remained similar between arms, at rates of 8.1% for acalabrutinib and 6.1% for placebo.
