VenR Achieves Strong Results in Japanese CLL/SLL Cohort

New data from a small cohort of Japanese patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) shows treatment with venetoclax (Venclexta; Abbvie/Genentech) and rituximab (Rituxan; Genentech/Biogen) achieved real-world responses that were similar to those in the phase 3 MURANO trial.

The findings are significant because CLL and SLL are rare in the Japanese population. The report was published in Journal of Clinical and Experimental Hematopathology.¹

Venetoclax is a B-cell lymphoma 2 inhibitor that was approved in 2019 in Japan for the treatment of relapsed or refractory CLL/SLL in combination with the chemoimmunotherapy drug rituximab. The regimen is known as VenR.

In the MURANO trial, VenR achieved strong progression-free survival (PFS) and minimal residual disease (MRD) outcomes among patients with relapsed or refractory CLL who had received at least 1 prior therapy. The most common grade 3 or 4 adverse event was neutropenia, and 3.1% of patients experienced grade 3 or 4 tumor lysis syndrome (TLS).²

Chronic lymphocytic leukemia and small lymphocytic leukemia are both rare in the Japanese population, and these study data show the effectivness of venetoclax and rituximab in these individuals| Image Credit: kapinon-stock.adobe.com

The study authors wrote that due to the relative rarity of CLL and SLL in Japan, it was important to better understand how VenR performed in real-world use among Japanese patients. They conducted a retrospective observational study of consecutive patients with CLL or SLL who were treated between 2019 and 2023 at 1 of 3 hospitals in Oita, Japan. Nine patients were identified; 7 had CLL and 2 had SLL. Eight patients were male.

One patient with SLL was prescribed VenR following relapse after prior therapy. Four patients were refractory to prior therapy, and 4 patients were intolerant of prior therapy. The median number of prior therapy lines was 1 (range,1-3). Six patients had previously received Bruton’s tyrosine kinase inhibitors. The median observation period after the start of venetoclax was 814 days, the authors said.

Overall, 7 patients achieved a complete response, 1 patient had a partial response, and 1 patient’s disease remained stable. The patient with stable disease discontinued venetoclax at 12 days due to pancytopenia, the authors said. Overall survival (OS) and PFS at 3 years (95% CI, 2.08-NA) were both 83.3%.

In terms of safety, the authors said 6 patients experienced grade 3 or above neutropenia, but they said it was managed by dose reduction and/or interruption. Grade 3 or above TLS and anemia were found in 1 patient each, the authors said.

Only 1 patient experienced a grade 5 adverse event. That patient was diagnosed with pneumonia due to COVID-19, but the authors said that patient was “immunosuppressed by cyclosporine for coexisting nephrotic syndrome due to long-standing membranous nephropathy.”

The authors noted that in a larger-scale study, dose interruptions of venetoclax did not significantly affect PFS, which the present study authors said indicates the importance of prioritizing patient safety.³

The authors also noted that nearly half of patients developed an infusion site reaction after rituximab administration, which they said shows that vigilance is warranted not only during venetoclax ramp-up, but also after rituximab.

Only 1 of the 9 patients in this series was positive for del17p. The authors noted that in the MURANO trial, all del17p-positive patients eventually developed clinical relapse. They said follow-up will be needed to see whether the single del17p-positive patient in this series will be able to sustain remission.

Overall, the authors said their findings align well with those of the MURANO trial.

“VenR for CLL/SLL showed a good response and safety in real-world Japanese CLL/SLL patients,” they concluded. “The long-term efficacy requires further observation.”

References

1. Saburi M, Nishikawa T, Miyazaki Y, et al. Real-world outcomes of venetoclax and rituximab for chronic lymphocytic leukemia/small lymphocytic lymphoma: A retrospective analysis of nine Japanese cases. J Clin Exp Hematop. 2024;64(2):152-155. doi:10.3960/jslrt.24014

2. Seymour JF, Kipps TJ, Eichhorst B, et al. venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120. doi:10.1056/NEJMoa1713976

3. Roeker LE, Fox CP, Eyre TA, et al. tumor lysis, adverse events, and dose adjustments in 297 venetoclax-treated cll patients in routine clinical practice. Clin Cancer Res. 2019;25(14):4264-4270. doi:10.1158/1078-0432.CCR-19-0361