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Zanubrutinib in treatment naïve del(17p) CLL/SLL
Figure 2. Subgroup analysis of overall response rate. Overall response rate presented as of November 1, 2019. Two-sided Clopper-Pearson 95% Confidence Interval (CI) are used. CLL: chronic lymphocytic lymphoma; ECOG PS: Eastern Cooperative Oncology Group performance status; LDH: lactate dehydrogenase; LDi: longest diameter; SLL: small lymphocytic leukemia. aPatients with any target lesion with longest diameter presented. bSix patients had RNA quantity/quality not sufficient for polymerase chain reaction amplification of immunoglobulin heavy chain variable (VH) region for sequencing. cPatients having anemia (≤110 g/L), thrombocytopenia (≤100x109/L), or neutropenia (≤1.5x109/L). d10 patients had missing data. e23 patients had insufficient metaphases available for analysis.
no opportunistic infections were reported.
Of other malignancies reported on study, most were
dermatological malignancies reported in ten patients (9.2%). Other than two patients with melanoma, all were basal and squamous cell carcinomas of the skin (grade 1/2) reported from patients in Australia and New Zealand, where skin cancers are frequent, especially in patients with CLL/SLL.30,31 One patient developed grade 3 melanoma requiring surgery and adjuvant therapy with pembrolizumab leading to discontinuation of zanubruti- nib. Five patients (4.6%) reported a non-dermatologic other malignancy. One patient developed localized breast cancer for which axillary lymph node biopsy indicated disease transformation to DLBCL, while one other patient developed lung cancer for which interlobar lymph node biopsy also indicated disease transformation to DLBCL. Three patients reported a transitional cell carcinoma of the bladder or ureter, all of whom underwent resection with-
out known residual disease and remain on study drug treatment.
The usage of therapeutic anticoagulation was not restricted on this study; 20 patients (18.3%) were reported to have taken a therapeutic anticoagulant including war- farin, direct-acting oral anticoagulants, and heparins dur- ing the study, while 27 patients (24.8%) were reported to have taken an oral platelet aggregation inhibitor, including aspirin, during the study. Bleeding of any type was report- ed in 47.7% of patients (4.6% grade ≥3). Major bleeding events were defined as any bleeding event with grade ≥3, any SAE, or any bleed affecting the central nervous system (CNS); these occurred in six patients (5.4%). A description of each event, including any confounding factors, is pre- sented in Online Supplementary Table S6; in two patients, bleeding occurred in the setting of a surgical procedure without dose hold as advised per protocol. All patients continued study treatment after dose interruption. No
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