Among patients with double-expressor lymphoma (DEL), Brukinsa (zanubrutinib) in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) proved to be an effective option, and the safety of Brukinsa is acceptable for patients, according to study findings published in Cancer.
According to the study, DEL refers to the simultaneous expression of the proteins MYC and BCL2 in the lymphoma tissue by means of immunohistochemical staining, without the presence of MYC and BCL2 gene rearrangements or translocations.
“These findings encourage us to initiate the multicenter, phase 3 clinical study, and the underlying mechanisms of [bruton tyrosine kinase inhibitor] on DEL are under investigation, as well as the prognostic factors,” study authors wrote.
After a median follow up of 29.3 months, the objective response rate was 89.6%, with a complete response (CR) rate of 83.3%. At two years, progression-free survival was 81.25%, and overall survival was 93.75%. Median progression-free survival and overall survival were not reached.
In addition, thirty-one patients (64.6%) remain in CR, while 12 patients (25%) experienced progressive disease (PD), including three who died due to PD after six treatment cycles. One patient died from cardiovascular disease after the second cycle at a non-research clinical center, and an autopsy was not performed, leaving it unclear whether the death was due to sudden death related to side effects. One patient died from a COVID-19 infection after eight cycles of treatment; this patient's efficacy evaluation remained CR.
Furthermore, next-generation sequencing results from 33 patients showed TP53, MYD88 and PIM1 were the most commonly mutated genes. Multivariate analysis found BCL-6 gene rearrangement was an adverse prognostic factor for both progression-free survival (75.3% lower risk) and overall survival (94.3% lower risk). The number of extranodal involvements also significantly affected overall survival (15.12 times higher risk).
Regarding safety, grade 3 (severe) side effects were shown in 23 of 48 (47.9%) patients. Neutropenia was the most common grade 3 or worse side effect, occurring in 18 patients (37.5%), followed by pulmonary infection in 11 (22.9%), febrile neutropenia in three (6.3%), anemia in four (8.3%) and thrombocytopenia in four (8.3%). Treatment was well tolerated with no dose reductions or interruptions, the study stated.
“The regimen is well tolerated, especially for patients [at least] 60 years old, who did not benefit from [ibrutinib R‐CHOP] in the Phoenix study,” study authors wrote.
In this multicenter, prospective, singe-arm, phase 2 clinical study, a total of 48 newly diagnosed patients were enrolled between November 2020 and July 2022. Patients received Brukinsa (160 milligrams [mg] orally, twice daily) for six months and rituximab (375 mg per square meter [mg/m²], day 0), cyclophosphamide (750 mg/m², day 1), doxorubicin (50 mg/m², day 1), vincristine (1.4 mg/m², day 1) and prednisone (100 mg, days 1 to 5) in repeated 21-day cycles for six to eight cycles.
The study's primary end goals are progression-free survival and overall survival, and secondary end goals included complete response rate, overall response rate and side effects.
Reference:
“Zanubrutinib plus R‐CHOP for the treatment of newly diagnosed double‐expressor lymphoma: A phase 2 clinical study,” by Xia Yin, et al., Cancer.
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