Real-world Data Show Higher Incidence of Neutropenia With Venetoclax, Obinutuzumab Combo in CLL

Across 19 patients, 73% developed grade 3 or 4 neutropenia, significantly higher than the incidence observed in the phase 3 trial examining the combination for chronic lymphocytic leukemia (CLL).

A single-center study has revealed a higher incidence of severe neutropenia associated with venetoclax in combination with obinutuzumab for patients recently diagnosed with chronic lymphocytic leukemia (CLL), with nearly 3 in 4 patients experiencing the adverse reaction.

Across the 19 patients, 73% developed grade 3 or 4 neutropenia, significantly higher than the incidence observed in the phase 3 CLL14 trial, which established a survival benefit with venetoclax—an oral selective B-cell lymphoma 2 inhibitor—and obinutuzumab—an anti-CD20 antibody. In the study, patients receiving the combination had superior progression-free survival.

“The incidence of grade 3-4 neutropenia reported in CLL-14 was reported to be 52.8% and 58% at long term follow up,” wrote the researchers. “By contrast, the MURANO trial examined the use of an anti-CD20 agent with venetoclax in the relapsed refractory setting and found the incidence of grade 3-4 neutropenia to be 57.7%. Data with respect to real world incidence is sparse.”

In the current retrospective study, patients had high-risk characteristics and comorbidities, which the researchers say could have contributed to the higher rate of neutropenia. Compared with the phase 3 studies, patients in the current study had higher rates of del 17p (26.3%), unmutated IGHV (89.5%), and TP53 mutations (26.3%). More than one third of these patients also received at least 1 prior treatment before the venetoclax and obinutuzumab combination.

During the study period, the mean time from treatment initiation to neutropenia was 42 days. There were 5 patients who developed infectious complications, 4 of which were part of the group that experienced neutropenia. Complications included bacterial pneumonia, septic arthritis, fungal infection, and Pneumocystis jirovecii pneumonia.

“The addition of monoclonal antibodies, such as anti-CD20 agents, have been known to be an independent factor for neutropenia both with and without chemotherapy,” explained the researchers. “This should be considered as a compounding factor for higher rates of neutropenia in this setting. Obinutuzumab also appears to be associated with higher rates of neutropenia as compared to its counterpart, rituximab.”

The researchers note that additional studies are needed to determine if proactive treatment with growth factor is effective at prolonging the duration of the treatment combination and to determine the effect of dose interruptions and modifications on survival.


Samuels C, Abbott D, Niemiec S, et al. Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. Cancer Rep. Published online July 12, 2021. doi:10.1002/cnr2.1505