The U.S. Food and Drug Administration granted accelerated approval on May 13 to sonrotoclax — brand name Beqalzi — for adults with relapsed or refractory mantle cell lymphoma who have received at least two prior lines of systemic therapy including a Bruton's tyrosine kinase inhibitor. [1] It is the first BCL2 inhibitor approved for mantle cell lymphoma, and the first new BCL2 inhibitor approved in the United States in a decade. The name is what catches first: sonrotoclax. The Latin diminutive of son- (sound) with -clax (the BCL2-inhibitor naming convention introduced by venetoclax). The brand name Beqalzi is pronounced "bee-KAHL-zee."

BCL2 is an anti-apoptotic protein that B-cell lymphomas overexpress to evade programmed cell death. Venetoclax (2016 for CLL, 2018 for AML) was the first-generation BCL2 inhibitor; sonrotoclax is more potent, more selective, with a shorter half-life and no accumulation. [2] In tumor lysis syndrome — the rapid breakdown that floods the bloodstream with potassium, phosphate, and uric acid — a shorter half-life means easier dose ramp-up in patients with high tumor burdens.

The approval rests on Phase 1/2 BGB-11417-201 (NCT05471843), 103 R/R MCL patients previously on anti-CD20 and a BTK inhibitor. [1] ORR by independent review (Lugano) was 52% (95% CI: 42, 62); median DoR 15.8 months at 11.9-month follow-up; CR rate 15.5%. [3] Warnings: tumor lysis syndrome, infections (pneumonia 10%), neutropenia. Regimen: four-week ramp-up to 320 mg PO daily.

Continued approval is contingent on the Phase 3 CELESTIAL-RRMCL trial of sonrotoclax plus zanubrutinib. [2] The combination work is where sonrotoclax matters most — early CLL data with zanubrutinib showed undetectable MRD rates no single class agent has touched. The MCL approval is the foot in the door for a broader B-cell program in CLL, Waldenström, myeloma, and AML; more than 2,200 patients have enrolled globally. [2]

For the ~3,000-4,000 new MCL diagnoses each year, R/R now has a non-BTK pill option. The molecule is named after a sound; the medicine extends a class that has, since 2016, rewritten what it means to die from a B-cell cancer.

-- KENJI NAKAMURA, Tokyo