Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma.

OBJECTIVE: To provide a comprehensive review of the pharmacokinetics, pharmacodynamics, safety, and efficacy of a new Food and Drug Administration (FDA) approved Bruton's tyrosine kinase inhibitor (BTKi), pirtobrutinib for relapsed/refractory mantle cell lymphoma (r/r MCL). DATA SOURCES: A literature search was conducted through PubMed MEDLINE, ClinicalTrials.gov, and the FDA website (January 2018-January 2023) using the following key terms: lymphoma, non-covalent, Bruton's tyrosine kinase (BTK), and relapse. Relevant English language monographs, studies, and abstracts conducted in humans were reviewed and considered. DATA SUMMARY: Pirtobrutinib, a novel non-covalent BTKi, was granted accelerated approval for treatment of r/r MCL on January 27th, 2023, based on an open-label, multi-center phase 1/2 BRUIN trial. In phase l, 61 patients with r/r MCL received seven dose levels of pirtobrutinib (25-300 mg). There was no reported maximum tolerated dose or dose-limiting toxicities during this study period. In phase 2, 56 r/r MCL evaluable efficacy patients received pirtobrutinib 200 mg daily. The overall response rate (ORR) was 52% (95% CI 38-65). Additionally, patients who received a previous covalent BTKi, ORR was 52% (95% CI 38-66). Neutropenia was the most common adverse reaction reported as a grade 3 or higher. CONCLUSION: Pirtobrutinib has demonstrated safety and efficacy in heavily pre-treated adult patients with r/r MCL. Advantages of this drug include its usage in patients whose malignancy is resistant to current BTKi, tolerability, and response rate. Multiple clinical trials are underway to determine the efficacy of pirtobrutinib in other B-cell malignancies.

Cytogenetic guided therapy using blinatumomab and inotuzumab ozogamicin in a patient with relapse/refractory acute lymphoblastic leukemia.

INTRODUCTION: Acute Lymphoblastic Leukemia (ALL) is an aggressive cancer that requires intense chemotherapy and has a high rate of recurrence. Treatments of Relapse/Refractory (R/R) B-cell ALL are limited. Blinatumomab, a bispecific T-cell engager (CD19/CD3) monocolonal antibody, and Inotuzumab Ozogamicin, an anti-CD22 antibody conjugate, are current recommended options. CASE REPORT: To describe a R/R B-cell ALL patient who failed blinatumomab therapy. Subsequently she received inotuzumab ozogamicin achieving a complete response. MANAGEMENT & OUTCOME: Our patient was initially treated with CALGB 10403 regimen but did not achieve a complete response. Blinatumomab was given for relapse/refractory disease however she had an incomplete response despite having 100% expression in CD19 markers. Consequently, she received inotuzumab ozogamicin attributable to 70% expression of CD22. She responded with a complete response and transitioned to a successful hematopoietic stem cell transplant. DISCUSSION: There is limited clinical guidance on the preferred treatment of adult R/R B-Cell ALL. Currently, there are no randomized head-to-head trials comparing efficacy of blinatumomab and inotuzumab ozogamicin. Clinical patterns of blinatumomab resistance has been reported. Our case study remains unclear of why our patient had unsuccessful outcomes with blinatumomab regardless of having CD19 positivity of 100%. Future prospective analysis and comparative studies are needed to determine proper sequencing of these therapies.