Brukinsa Viabie for Calquence-Intolerant B-Cell Malignancies

Patients with B-cell malignancies who were intolerant to prior treatment with Calquence (acalabrutinib) experienced clinically meaningful benefits with Brukinsa (zanubrutinib), showing the viability of Brukinsa in this patient population, according to data presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

Results from the ongoing phase 2 BGB-3111-215 study showed data from a cohort of 27 patients intolerant to Calquence. The median exposure to Brukinsa lasted six months longer than the patient’s cumulative exposure to Calquence before treatment discontinuation at 11.4 months versus 5.4 months, respectively.

Further, 70% of the Calquence intolerance side effects experienced by patients did not reoccur at any grade with Brukinsa. Of those that did recur, no events recurred at a higher severity. The most common grade 2 or higher Calquence intolerance side effects that recurred during treatment with Brukinsa included arthralgia (joint pain, six events), headache (five events), myalgia (muscle pain, five events), diarrhea (three events), rash (three events), fatigue (two events) and hemorrhage (two events).

According to Dr. Mazyar Shadman, who presented these data at the 2023 ASH meeting, no side effects led to death, but two side effects led to treatment discontinuation of Brukinsa. Other patients discontinued Brukinsa due to physician decision (two patients), patient withdrawal (two patients) and progressive disease (PD; one patient). The side effects that led to discontinuation of Brukinsa were a recurrence of grade 2 myalgia in one patient and grade 3 diarrhea in another.

Looking at grade 3 or higher side effects, three patients experienced a neutrophil count decrease after Brukinsa, but anemia, thrombocytopenia, nor platelet count decrease occurred. Overall, seven patients had a serious side effect with 16 of those leading to dose interruption and six leading to dose reduction.

In the phase 2 study, patients with previously treated B-cell malignances included those with chronic lymphocytic leukemia (CLL; 17 patients), small lymphocytic lymphoma (SLL; two patients), Waldenström’s macroglobulinemia (four patients), mantle cell lymphoma (two patients) or marginal zone lymphoma (two patients). To be enrolled in the study, they had to be deemed intolerant of a prior Bruton tyrosine kinase (BTK) inhibitor treatment and could not have either Richter transformation or PD while on BTK treatment. In the first cohort of the study, 57 patients intolerant to Imbruvica (ibrutinib) were enrolled. In cohort 1 and 2, patients were given either 160 mg of Brukinsa twice a day or 320 mg once a day.

The median age of patients in cohort 2 was 73, with a majority of male patients (63%); most had an ECOG performance status of 0 (67%), meaning they could perform daily tasks with no assistance.

According to Shadman, associate professor in the clinical research division and innovators Network Endowed Chair at the Fred Hutch Cancer Center, previous findings from the first cohort showed similar promise with Brukinsa after ibrutinib. In cohort 2, 19 of the Calquence-intolerant patients received the 160 mg dose and 8 received the 320 mg dose. Thirteen of the 27 patients intolerant to Calquence were also intolerant to previous use of ibrutinib, with 12 given a prior ibrutinib monotherapy and 1 patient on an ibrutinib combination therapy.Twenty-six patients intolerant to Calquence received the BTK as a monotherapy and one patient was intolerant to an Calquence combination regimen.

Twenty-five of the patients in cohort 2 were evaluable for efficacy after Brukinsa treatment. Investigators observed a 96% disease control rate, defined as patients with stable disease (SD) or better with Brukinsa. There was an overall response rate of 64%, defined as having a minor response or better, to the next-generation BTK inhibitor.

Overall, 48% of patients had a partial response, 4% had a very good partial response, 4% had a minor response, 32% had SD and 4% had progressive disease. The median time to best overall response was three months and time to the first overall response was seen at a median of 2.9 months. Of the patients with either CLL or SLL, 71% had a partial response with lymphocytosis or better.

“The results of this study demonstrated that (Brukinsa) may be a viable option for patients who are intolerant of (Calquence),” concluded Shadman.

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