RESUMO
Pirtobrutinib is a highly selective, non-covalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) were treated with fixed-duration pirtobrutinib plus venetoclax (PV) or pirtobrutinib plus venetoclax and rituximab (PVR) in this phase 1b trial (NCT03740529). Prior covalent BTKi therapy was allowed, but not prior venetoclax. Patients were assigned to receive PV (n=15) or PVR (n=10) for 25 cycles. Median age was 66 years (range, 39-78). Median prior lines of therapy was 2 (range, 1-4), and 17 (68%) patients had received prior covalent BTKi. At the data-cutoff date (May 5, 2023), median time on study was 27.0 months for PV and 23.3 months for PVR. Overall response rates were 93.3% (95% CI:68.1-99.8%) for PV and 100% (95% CI:69.2-100.0%) for PVR, with 10 complete responses (PV:7; PVR:3). After 12 cycles of treatment, 85.7% (95% CI:57.2-98.2%) of PV and 90.0% (95% CI:55.5-99.7%) of PVR patients achieved undetectable minimal residual disease assessed in peripheral blood by clonoSEQ® assay at a sensitivity of <1x10-4. Progression-free survival at 18 months was 92.9% (95% CI: 59.1-99.0) for PV patients and 80.0% (95% CI: 40.9-94.6) for PVR patients. No DLTs were observed in either treatment combination during the 5-week assessment period. The most common grade ≥3 adverse events for all patients included neutropenia (52%) and anemia (16%). Adverse events led to dose reduction in 3 patients and discontinuation in 2. In conclusion, fixed-duration PV or PVR was well tolerated and had promising efficacy in patients with R/R CLL, including patients previously treated with a covalent BTKi.
RESUMO
Venetoclax is a BCL2 inhibitor used in chronic lymphocytic leukemia (CLL) which can cause tumor lysis syndrome (TLS). We aimed to determine the incidence of and risk factors for TLS among patients with CLL/small lymphocytic lymphoma (SLL) who received treatment with venetoclax at our institution from 1/1/2016 to 12/31/2020. We included 616 venetoclax escalations among 136 pts with CLL. 74 pts (54%) underwent escalation exclusively outpatient, 35 (26%) had at least one planned hospitalization and 27 (20%) were escalated exclusively inpatient. During venetoclax initiation, 86% of pts received allopurinol, 71% intravenous hydration, 18% phosphate binders, and 10% prophylactic rasburicase. Among the entire cohort, 7 pts (5.1%) developed laboratory TLS by modified Cairo Bishop criteria and none developed clinical TLS. Incidence of laboratory TLS was 15% for those escalated exclusively inpatient, 2.9% for those with any prophylactic hospitalization and 2.7% for those escalated exclusively outpatient. Those who developed TLS were more likely to have higher TLS risk, and no additional risk factors were identified. In this single institution retrospective cohort study, laboratory TLS was observed, though clinical TLS was not. Prophylactic measures, including use of IV hydration, may have contributed to low rates of observed TLS in the outpatient setting.