A meta-analysis of 4 sonrotoclax cohorts showed consistent response activity and low tumor lysis rates in heavily pretreated mantle cell lymphoma.
Sonrotoclax (Beqalzi)–based regimens produced consistent responses across cohorts of patients with heavily pretreated relapsed/refractory mantle cell lymphoma (MCL), according to a systematic review and meta-analysis presented in a poster session at the
The analysis pooled 4 prospective, single-arm cohorts, including cohorts from the from the phase 1/2 BGB-11417-201 trial (NCT05471843), with 145 patients in total. The pooled odds ratio (OR) for overall response rate (ORR) was 3.84 (95% CI, 2.41-6.12; P < .001), and the pooled OR for complete response (CR) rate was 2.17 (95% CI, 1.28-3.69; P = .004).
In the pivotal cohort of BGB-11417-201, sonrotoclax monotherapy produced an ORR of 53.4% (n = 103; 95% CI, 43.4%-63.2%). The ORR was 50.0% (95% CI, 29.9%-70.1%) in the recommended phase 2 dose (RP2D) cohort (n = 24), 70.0% (95% CI, 34.8%-93.3%) in the sonrotoclax plus zanubrutinib (Brukinsa) cohort (n = 10), and 37.5% (95% CI, 8.5%-75.5%) in an additional monotherapy cohort (n = 8).
CR rates were 15.5% (95% CI, 9.2%-24.0%) in the pivotal cohort, 12.5% (95% CI, 4.4%-29.0%) in the RP2D cohort, 30.0% (95% CI, 6.7%-65.2%) in the combination cohort, and 12.5% (95% CI, 0.3%-52.7%) in the additional cohort. In the RP2D cohort, the median duration of response was 15.8 months.
“While we've had quite a few approvals lately [in the post-BTK inhibitor space, this] is still an area where more drugs are needed, and sonrotoclax slotting in there provides another option for patients [for whom] you would consider pirtobrutinib or in patients who may progress on pirtobrutinib and still not be able to get to CAR [chimeric antigen receptor] T-cell therapy,” said Tycel Phillips, MD, in an
Phillips is an associate professor in the Department of Hematology and Hematopoietic Cell Transplantation in the Division of Lymphoma at City of Hope in Duarte, California.
Key takeaways from the sonrotoclax meta-analysis in R/R MCL
Sonrotoclax selectively targets BCL-2, and in May 2026, the FDA granted it accelerated approval for adult patients with relapsed/refractory MCL who have received at least 2 lines of systemic therapy, including a BTK inhibitor.
In the analysis, investigators searched 5 databases including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library, and found 876 records.1 That number fell to 452 unique records after duplicates were removed.
Of the 38 articles reviewed in full, 4 studies went into the pooled analysis. The investigators evaluated ORR and CR rate as the primary end points, and hematologic adverse effects (AEs) of grade 3 or higher and tumor lysis syndrome (TLS) as safety end points.
Investigators also pooled the data with a random-effects model in Stata 18.0, and all 4 studies were judged low risk on the Risk of Bias 2.0 tool.
The median number of prior lines of therapy in each cohort broke down as 3 (range, 1-8) in the pivotal cohort, 4 (range, 2-9) in the RP2D cohort, 3 (range, 2-7) in the combination cohort, and 3 (range, 2-6) in the additional cohort.
“Given what we know so far about the rationale for BTK inhibitor resistance and MCL, if you have a patient with early progression on a BTK inhibitor, then maybe …sonrotoclax would fit vs pirtobrutinib in that situation. Ideally, in this space with approved options, the goal should still be to get a patient to CAR T-cell therapy,” Phillips explained.
The pivotal BGB-11417-201 cohort accounted for 40.2% of the weight in the ORR analysis, and its OR for ORR was 2.68 (95% CI, 1.62-4.47). The ORs were 3.52 (95% CI, 1.62-7.65) in the RP2D cohort, 5.83 (95% CI, 2.18-15.60) in the combination cohort, and 2.91 (95% CI, 0.93-9.13) in the additional cohort for ORR. For CR rate, the ORs for these respective cohorts were 1.96 (95% CI, 1.01-3.81), 2.46 (95% CI, 0.91-6.67), 2.88 (95% CI, 0.93-8.94), and 1.61 (95% CI, 0.45-5.81).
Neutropenia was the most frequent grade 3 or higher hematologic AE with a pooled incidence of 19.3% (95% CI, 13.1%-26.8%). The pooled incidence of grade 3 or higher thrombocytopenia was 8.2% (95% CI, 4.3%-14.1%), anemia 6.9% (95% CI, 3.4%-12.7%), and febrile neutropenia 4.8% (95% CI, 2.1%-9.7%). Additionally, clinical TLS developed in 1.4% (95% CI, 0.2%-4.9%) of patients.
“The fact that sonrotoclax has accelerated approval will make it easier for even some investigator-initiated studies, as you could actually access this medication as a standard of care vs having to get medication from the sponsor, which sometimes can be a bit difficult if it doesn’t align with their agenda at that point in time,” said Phillips on the next steps for the agent.
