The phase II PrE0405 trial met its primary endpoint, achieving a complete response rate of 85% in 33 patients with mantle cell lymphoma over age 60 who received bendamustine and rituximab, a standard chemoimmunotherapy regimen, along with venetoclax, which is investigational in this setting. The combination was generally well tolerated, a notable finding, according to Craig A. Portell, MD, who presented the data at the 2023 ASH Annual Meeting & Exposition (Abstract 733).
"We are encouraged by the promising results of study PrE0405 as a potential improvement in first-line treatment for our older patients with mantle cell lymphoma," said Dr. Portell, lead investigator for the study and a medical oncologist at the University of Virginia Comprehensive Cancer Center.
Mantle cell lymphoma is a form of non-Hodgkin lymphoma that more often affects men and people over age 60. Although mantle cell lymphoma is not curable for most people, treatment can reduce the extent of the disease and put it into remission for years. Still, it is a clinical challenge due to high relapse rates.
"With a median age of 60 to 70 years at diagnosis, many patients with mantle cell lymphoma are ineligible for aggressive treatments," said Dr. Portell. "In PrE0405, we observed an 85% complete response rate from a lower-intensity therapy."
PrE0405
This single-arm phase II trial aimed to evaluate the effectiveness of bendamustine and rituximab chemoimmunotherapy in combination with venetoclax as first-line treatment for patients over 60 with mantle cell lymphoma. The primary analysis was conducted on 33 patients enrolled between January 2020 and March 2022 by PrECOG investigators at multiple clinical sites in the United States. The median age of participants was 71 years (range = 61–80); 76% (n = 25) were male.
All patients had measurable or evaluable disease, defined as a lymph node measuring > 1.5 cm or a spleen malignancy of > 15 cm. Nine patients (27%) had high-risk blastoid histology and 22 (67%) had high-risk MIPI scores. This suggests that patients enrolled were at higher risk by these measures.
All patients received bendamustine, rituximab, and venetoclax for six 28-day cycles. Seven patients (21%) over age 75 received a lower dose of bendamustine at the treating physician's discretion.
It is common among patients with mantle cell lymphoma to continue with rituximab after initial treatment, and this was encouraged in this trial per physician discretion. Maintenance rituximab was administered in 19 of 33 patients (57%).
An interim analysis was conducted after 19 patients enrolled to look for tumor-lysis syndrome; laboratory evidence of tumor-lysis syndrome was seen in 2 of 33 patients during cycle 1 only, and clinical tumor-lysis syndrome was not seen.
The primary endpoint was the positron-emission tomography (PET)-negative complete response rate at the end of treatment, using the Lugano criteria. This treatment was considered promising if ≥ 23 patients attained complete response. An overall response was observed in 97% of patients (32 of 33). PET-negative bone marrow biopsies performed at the end of treatment confirmed a complete response rate of 85% (28 of 33).
Treatment was generally well tolerated, though gastrointestinal toxicities were common. Adverse events during therapy included lymphopenia (n = 9, 27%), neutropenia (n = 5, 15%), and thrombocytopenia (n = 5, 15%). Gastrointestinal adverse events of all grades were nausea/vomiting (n = 26, 79%), fatigue (n = 17, 52%), and diarrhea (n = 10, 30%). Grade ≥ 3 toxicities occurred in 19 patients (58%).
Secondary endpoints include adverse event rates, overall response rate, progression-free survival, and overall survival. Testing for measurable residual disease was performed by next-generation sequencing on bone marrow specimens and peripheral blood samples collected at the end of treatment.
Disclosure: This study was supported by Genentech, Member of the Roche Group. For full disclosures of the study authors, visit ash.confex.com.
