Pirtobrutinib has been approved for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma in China.
The BTK inhibitor pirtobrutinib (Jaypirca) has been approved by China’s National Medical Products Administration (NMPA) for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).1 The decision reflects the
BRUIN CLL-321 evaluated pirtobrutinib monotherapy (n = 119) vs either idelalisib (Zydelig) plus rituximab (Rituxan; IR) or bendamustine plus rituximab (BR; n = 119) in patients with relapsed/refractory CLL or SLL.3 Patients in the pirtobrutinib arm experienced a median progression-free survival (PFS) of 14.0 months compared with 8.7 months for patients in the IR or BR arm (HR, 0.54).1 In addition to median PFS improvements, rates of treatment discontinuations due to treatment-emergent adverse events (TEAEs) were lower in patients who received pirtobrutinib (5.2%) compared with those who received IR or BR (21.1%).
“There is an urgent clinical need for new [CLL and SLL] treatment. As a next‑generation, noncovalent and reversible BTK inhibitor, pirtobrutinib represents an important advancement for patients with relapsed or refractory CLL,” lead study author Lu-Gui Qiu, MD, stated in a news release. “We believe [pirtobrutinib] will offer an important treatment option for patients with CLL/SLL in China and help meet the needs of long‑term disease management in the future.”
Qiu is a professor and head of the Lymphoma and Myeloma Center at the China Academy of Chinese Medical Sciences in Beijing.
The randomized, open-label study enrolled patients with relapsed/refractory CLL/SLL who had received prior covalent BTK inhibition. Patients also needed to have an ECOG performance status of 2 or less and an absolute neutrophil count of 0.75 x 109/L or less.2
If patients had a history of drug-related liver injuries, prior Richter transformation, history of involvement of the central nervous system, or cardiovascular disease, they were not included in the trial.
Patients received once-daily oral pirtobrutinib at 200 mg or at IR or BR per the labeled dosages.1
PFS per the 2018 International Workshop on CLL criteria was the trial’s end point. Secondary end points for the trial were overall response rate (ORR), duration of response (DoR), event-free survival (EFS), time to next treatment (TTNT), safety, and overall survival (OS).
“The approval of pirtobrutinib for the CLL/SLL indication in China marks an important milestone in the treatment journey for Chinese [patients with] CLL/SLL. It means that patients who continue to experience disease progression after covalent BTK inhibitor therapy can now gain timely access to this globally innovative treatment option,” Li Wang, MD, PhD, added in the news release.
Wang is a senior vice president and the head of Lilly China Drug Development and Medical Affairs Center, both for Eli Lilly China in Shanghai.
Previously reported data from the trial showed patients in the pirtobrutinib arm achieving an 18-month OS rate of 73.4% (95% CI, 63.9%-80.7%), whereas patients who received IR or BR demonstrated a rate of 70.8% (95% CI, 60.9%-78.7%).3
Regarding safety, the most common TEAEs in the pirtobrutinib arm were anemia (20.7%), pneumonia (19.8%), neutropenia (16.4%), and diarrhea (15.5%). Common TEAEs for patients in the IR or BR arm were diarrhea (29.4%), pyrexia (25.7%), nausea (20.2%), fatigue (18.3%), and COVID-19 (18.3%). Notably, dose reductions due to TEAEs were lower in the pirtobrutinib arm (7.8% vs 28.4%), in addition to grade 3 or higher TEAEs (55.2% vs 71.6%).
“The approval in China for CLL/SLL represents a significant breakthrough in this field, which ensures that [patients with] CLL/SLL in China have timely access to this global therapeutic innovation,” Hui Zhou, MD, PhD, added in the news release.
Zhou is the chief of research and development in oncology at Innovent Biologics in Suzhou, China.
