Brukinsa, which was approved in September 2021, resulted in better oucomes for certain patients with with Waldenström macroglobulinemia, according to the ASPEN clinical trial.
Brukinsa led to higher complete response (no evidence of cancer left) or very good partial response rates than Imbruvica (ibrutinib) for patients with Waldenström macroglobulinemia that harbored a MYD88 mutation, according to long-term follow-up from the phase 3 ASPEN trial.
Findings were recently presented at the 2022 ASCO Annual Meeting.
At a median follow-up of 44.4 months, findings showed that patients with MYD88-mutated Waldenström macroglobulinemia who were enrolled to cohort 1 achieved a complete response or very good partial response rate of 36.3% with Brukinsa (98 patients) compared with 25.3% with Imbruvica (101 patients). Notably, the response rate of complete response or very good partial response was noted to be numerically higher at all time points with Brukinsa compared to Imbruvica in this population.
Moreover, the median time to complete response or very good partial response was shorter in the Brukinsa group compared to the Imbruvica group, at 6.7 months and 16.6 months, respectively. The event-free rate for the duration of complete response or very good partial response at 24 months was also found to be higher in the investigative group than the control arm, at 90.6% and 79.3%.
“Although not statistically significant at (the previously reported) primary analysis, a consistent trend of deeper, earlier, and more durable responses complete response or very good partial response was observed (with Brukinsa compared with Imbruvica),” lead study author Dr. Constantine S. Tam, the program lead for Chronic Lymphocytic Leukemia and Low-Grade Lymphoma at Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues, wrote in a poster on the findings.
Prior ASPEN data showed that at a median follow-up of 19.4 months Brukinsa elicited a complete response or very good partial response rate of 28.4% compared with 19.2% with Imbruvica in patients with MYD88-mutated Waldenström macroglobulinemia. In September 2021, the FDA approved Brukinsa for the treatment of adult patients with Waldenström macroglobulinemia, based on those findings.
To enroll on ASPEN, patients were required to be at least 18 years of age and have a diagnosis of Waldenström macroglobulinemia. They also needed to have measurable disease requiring treatment; an ECOG performance status (which measures a patient’s ability to complete daily tasks) of 0 to 2; adequate bone marrow, renal and hepatic function; and a life expectancy of more than four months. Patients who had not received prior treatment for their disease were required to be considered inappropriate candidates for a standard chemoimmunotherapy regimen.
A total of 201 patients with MYD88-mutated Waldenström macroglobulinemia were enrolled to cohort 1, and 28 patients with MYD88 wild-type disease comprised cohort 2.
Patients in cohort 1 were randomly assigned to receive oral Brukinsa at a twice-daily dose of 160 mg (102 patients), or oral Imbruvica at a once-daily dose of 420 mg (99 patients). Treatment continued in both arms until disease progression. All patients in cohort 2 were administered 160 mg of Brukinsa twice daily until disease progression.
The main goal of the trial was complete response or very good partial response in cohort 1. Secondary end points included further comparison of efficacy, clinical benefit, anti-lymphoma effects, and safety of Brukinsa vs Imbruvica in cohort 1. The efficacy and safety of Brukinsa in cohort 2 served as exploratory end points.
Additional data from cohort 1 showed that both the median overall survival (time from treatment until death of any cause) and progression-free survival (time from treatment until disease gets worse) were not reached. However, investigators noted that statistical estimates favored Brukinsa for overall survival and progression-free survival.
The 42-month overall survival rates were 87.5% and 85.2% for Brukinsa and Imbruvica, respectively; the 42-month PFS rates were 78.3% and 69.7%, respectively.
Notably, patients with CXCR4-mutated disease were noted to achieve deeper and faster responses with Brukinsa (20 patients), as well as favorable progression-free survival over Imbruvica (33 patients). The 42-month PFS rates in the investigative and control arms were 73.2% and 49.0%, respectively. Among this subset, 21.2% of patients achieved a very good partial response or better with Brukinsa, compared to 10.0% of those who received Imbruvica. Major responses occurred in 78.8% and 65.0% of patients, respectively, and overall responses occurred in 90.9% and 95.0% of patients, respectively.
In the subset of patients with CXCR4 wild-type disease, Brukinsa (65 patients) elicited a very good partial response or better rate of 44.6% and 30.6% with Imbruvica (72 patients). Major responses were experienced by 83.1% and 84.7% of patients, respectively. Lastly, the overall response rate achieved with Brukinsa in this subset was 96.9% compared to 94.4% with Imbruvica.
In cohort 2, Brukinsa elicited one complete response, a complete response or very good partial response rate of 31%, and a major response rate of 65%. Event-free rates of overall survival and progression-free survival at 42 months were 83.9% and 53.8%, respectively.
Regarding safety in cohort 1, 99% and 100% of patients, respectively, experienced at least one side effect of any grade in the Brukinsa and Imbruvica groups. The rates of grade 3 or higher side effects were 74.3% and 72.4%, respectively. Moreover, 3.0% and 5.1% of patients who received Brukinsa and Imbruvica, respectively, experienced side effects that resulted in death; 8.9% and 20.4% of patients experienced side effects leading to treatment discontinuation; and 15.8% and 26.5% of patients had side effects that led to a dose reduction.
In cohort 1, grade 3 or higher side effects reported in the Imbruvica and Brukinsa arms, respectively, included diarrhea (2.0% vs 3.0%), upper respiratory tract infection (1.0% vs 0%), muscle spasms (1.0% vs 0%), arthralgia (0% vs 3.0%), hypertension (19.4% vs 9.9%), nosebleeds (0% vs 1.0%), atrial fibrillation (6.1% vs 2.0%), fatigue (1.0% vs 1.0%), pneumonia (10.2% vs 1.0%) and fainting (6.1% vs 5.0%).
Grade 3 or higher side effects of interest reported in the control and investigative arms, respectively, comprised infection (27.6% vs 21.8%), bleeding (10.2% vs 8.9%), diarrhea (2.0% vs 3.0%), hypertension (20.4% vs 9.9%), atrial fibrillation/flutter (8.2% vs 2.0%), anemia (6.1% vs 11.9%), neutropenia (10.2% vs 23.8%), thrombocytopenia (6.1% vs 10.9%), second primary malignancy (3.1% vs 5.9%) and non–skin cancers (3.1% vs 4.0%).
“Fewer (side effects) leading to treatment discontinuation, dose reductions, and deaths occurred in the (Brukinsa) arm,” the study authors concluded. “Cumulative incidences of atrial fibrillation, diarrhea, hypertension, muscle spasm, and pneumonia were lower in patients receiving (Brukinsa). Despite a higher rate of neutropenia in the (Brukinsa) arm, infection rates were similar and more patients in the (Imbruvica) arm had grade (3 or higher) infections.”
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