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VenR Achieves Strong Results in Japanese CLL/SLL Cohort

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are rare in Japan, but a new report affirms the effectiveness of venetoclax (Venclexta) and rituximab (Rituxan) (VenR) in this population.

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

asian patient | Image Credit: kapinon-stock.adobe.com

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

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