In CLL/SLL, the efficacy of pitubrutinib/pitobrutinib is non-inferior to ibrutinib

Based onBRUIN Phase 3 Results from the CLL-314 trial (NCT05254743) in patients with previously treated or treated de novo chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SL) L) In patients, the objective response rate (ORR) of Pirtobrutinib/Zeparib was non-inferior to that of ibrutinib.

Pitobrutinib met the primary endpoint of ORR non-inferiority in both the pretreatment and intention-to-treat populations of the trial, as assessed by the independent review committee. In addition, the ORR was nominally more inclined to pitubrutinib and ibrutinib (P<0.05). Data on progression-free survival (PFS), a key secondary endpoint, were not yet mature at the time of analysis, although current results tend to favor pitubrutinib. The researchers plan to formally testPFS in future analyses. Additionally, pitobrutinibtreatment did not show an impairment in overall survival (OS).

The safety profile of pitubrutinib in the BRUIN CLL-314 trial was comparable to previous reports of this drug. Clinical trials include head-to-head studies against modern standards of care, as well as examinations of patient populations that reflect real-world use, such as patients pretreated with Bruton's tyrosine kinase [BTK] inhibitors. In the open-label Phase 3 BRUIN CLL-314 trial, 650 patients were randomly assigned to receive either pitubrutinib 200 mg orally once daily or ibrutinib 420 mg orally once daily. The head-to-head trial included 225 patients treated for early-stage CLL or SLL.

The trial's primary endpoint was ORR as assessed by a blinded independent review committee Secondary endpoints included each investigator and independent review committee assessment of PFS, duration of response, event-free survival, time to next treatment, OS, safety and tolerability, and patient-reported outcomes. According to the CLL 2018 International Symposium criteria, patients 18 years and older with confirmed CLL or SLL requiring treatment are eligible to participate in the trial. 2 Additional eligibility criteria include known 17p deletion status in trial part 1, confirmed 17p deletion by fluorescence in situ hybridization testing in trial part 2, ECOG performance status 0 to 2, and normal organ function.

Known or suspected to have diffuse leukemia at any time before enrollmentPatients with B-cell lymphoma, prolymphocytic leukemia, or Richter transformer of Hodgkin lymphoma; known or suspected central nervous system involvement; or patients with a history of renal, neurological, psychiatric, endocrine, metabolic, or immune disease were not eligible for inclusion in the study. Active cytomegalovirus infection was also a reason for exclusion from the trial.

According to the press release, pitubrutinib is currently indicated for the treatment of adults with relapsed/refractory mantle cell lymphoma following 2 prior systemic therapies, including a BTK inhibitor. It may also be used to treat adults with CLL or SLL who have received 2 or more prior therapies, including BTK inhibitors and BCL-2 inhibitors. Safety information for pitubrutinibincludes warnings about infection, bleeding, and cytopenias. Other potential adverse reactions include cardiac arrhythmias, second primary malignancies, hepatotoxicity, and embryo-fetotoxicity.

Reference materials:https://www.cancernetwork.com/view/pirtobrutinib-yields-noninferior-orr-vs-ibrutinib-in-cll-sll