orelabrutinib therapy in patients with r/r b-cell lymphoma intolerant to other bruton tyrosine kinase inhibitors

Conditions: B-cell Lymphoma

Summary: to evaluate the safety and effecacy of orelabrutinib therapy in patients with relapsed or refractory b-cell lymphoma (including r /rcll/sll and r /rmcl) who are intolerant to ibrutinib/zanubrutinib or other btk inhibitors

the efficacy of first-generation btki ibrutinib in the treatment of b-cell lymphoma is reasonable, but the kinase selectivity is poor and the off-target effect is increased. it is associated with non-btk-related adverse reactions such as bleeding, atrial fibrillation, diarrhea and rash.this is the reason why some patients stop taking btki and cannot benefit from long-term treatment. orelabrutinib kinase is highly selective. the safety of the treatment of 266 chinese patients with b-cell malignancies (including r/r cll/sll, r/r mcl, r/r wm, r/r mzl, r/r cnsl) showed that no ≥ grade 3 atrial fibrillation occurred.the incidence of grade 3 diarrhea and severe bleeding adverse events was lower than that of ibrutinib and zanubrutinib.therefore, the aim of this study was to evaluate the safety and efficacy of self-selected switching to obrutinib in patients with relapsed or refractory b-cell lymphoma intolerant to ibrutinib/zanubrutinib therapy

Eligibility criteria:
inclusion criteria: * 1) age ≥18 years, both sexes; 2) confirmed by the following diagnostic criteria cll/sll: relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma confirmed by flow cytometry or histopathology according to iwcll2018 criteria mcl: recurrent or refractory mantle cell lymphoma histopathologically confirmed: including cytogenetic testing t (11;14) mantle cell lymphoma with positive/high immunohistochemical expression of cyclin d1 3) previous treatment with ibrutinib/zanubrutinib/or other btk inhibitors and any of the following conditions were defined by the investigator as poor tolerance to ibrutinib/zanubrutinib or other btk inhibitors: a) grade ≥2 nonhematologic toxicity lasting \>7 days with or without treatment; b) any non-hematological toxicity of ≥ grade 3 ; c) grade 3 neutropenia with infection or fever; d) grade 4 hematologic toxicity that persisted until the investigator chose to discontinue ibrutinib/ zanubrutinib or other btk inhibitors due to toxicity rather than disease progression 4) the investigator-initiated treatment decision to use orelabrutinib (before study enrollment); 5) life expectancy ≥3 months; 6) the patient or his or her legal representative voluntarily signed written informed consent exclusion criteria: * 1) richter conversion (cll/sll) or disease progression during treatment with ibrutinib/ zanubrutinib or other btk inhibitors; 2) past treatment with orelabrutinib; 3) absolute neutrophil anc\ 2 times the upper limit of normal uln (unless gilbert syndrome is diagnosed), ast or alt\>2.5× uln; serum creatinine (cr) \>1.5×uln 5) coagulation function: inr and aptt ≤1.5 × uln; 6) grade 3 or 4 adverse events related to ongoing unresponded treatment with ibrutinib/ zanubrutinib or other btk inhibitors 7) participate in research projects that use interventions outside the scope of routine clinical practice