Venetoclax Yields Positive ORR But Poor PFS in R/R Mantle Cell Lymphoma

Patients with high-risk relapsed/refractory mantle cell lymphoma (MCL) who were treated with venetoclax (Venclexta) appeared to respond positively to treatment, although progression-free survival (PFS) was poor, according to findings from a study published in Blood Advances.

“Venetoclax may have a better role in MCL in earlier lines of treatment and possibly in combination with other agents,” according to the authors of a study published in Blood Advances.

In a population of 67 patients with data available for response assessment, venetoclax alone or as part of a combination therapy elicited an overall response rate (ORR) of 40%, which included a complete response rate of 16% and partial response rate of 24%.

Additionally, of 16 patients who received venetoclax in combination with a Bruton tyrosine kinase (BTK) inhibitor, 63% received prior treatment with a BTK inhibitor for a median of 7 months (range, 1-51) and achieved an ORR of 40%. In patients who were previously treated with a BTK, subsequent treatment with venetoclax plus a BTK inhibitor yielded an ORR of 33%,

A univariate logistic regression analysis indicated that receiving more than 3 lines of treatment before venetoclax was the only factor that significantly correlated with response (odds ratio [OR], 0.26; 95% CI, 0.08-0.90; P = .033).

With a median follow-up of 16.4 months, the median PFS and overall survival (OS) was 3.7 months (95% CI, 2.3-5.6) and 12.5 months (95% CI, 6.2-28.2), respectively, following venetoclax treatment initiation. Additionally, investigators reported 2-year PFS and OS rates of 13.8% (95% CI, 6.9%-23.1%) and 37.1% (95% CI, 24.0%-50.2%), respectively.

“Venetoclax may have a better role in MCL in earlier lines of treatment and possibly in combination with other agents,” the study authors stated. “However, effective treatment options following BTK [inhibitor] failure in MCL are limited, and these outcomes with venetoclax compare favorably with those achieved with other currently available treatments [including lenalidomide (Revlimid) and PI3K inhibitors], which make venetoclax a reasonable option as a bridge to CAR T cells or allogeneic [hematopoietic cell transplantation] in eligible patients.”

Investigators of this study retrospectively reviewed data of patients 18 years and older with relapsed or refractory MCL who were treated with venetoclax alone or in combination with other agents across 12 medical centers in the United States between January 1, 2010 and November 1, 2019. Investigators determined MCL International Prognostic Index (MIPI) scores for each patient with available data.

Univariate logistic regression models helped estimate the relationship between patient characteristics and ORR. Additionally, investigators estimated PFS and OS through the Kaplan-Meier method and compared them using the log-rank test.

Of 81 patients, 50 received single-agent venetoclax while others received a combination regimen that included a BTK inhibitor (20%) or anti-CD20 monoclonal antibody (14%). The median patient age at diagnosis was 64 years (range, 38-87), and most patients were male (78%) with stage III or IV disease (95%).

Additionally, most patients had a high MIPI score (49%). A total of 61% of patients had Ki-67 expression in over 30% of tumor cells, 29% had blastoid or pleomorphic histology, 34% had complex karyotyping, and 49% had TP53 alterations.

Overall, most patients received intensive chemotherapy as first-line treatment (51%). Additionally, 36% of patients received maintenance with rituximab (Rituxan) following first-line therapy. The median number of therapies prior to venetoclax initiation was 3 (range, 1-8), which included an anti-CD20 monoclonal antibody in 99% of patients, an alkylator in 93%, and a BTK inhibitor in 91%.

The median time from diagnosis to beginning venetoclax treatment was 3.9 years (range, 0.2-17.8). The median treatment duration with venetoclax was 2.8 months (range, 0.1-30.0).

Multivariate analyses indicated that having a high-risk MIPI score prior to venetoclax correlated with an inferior OS (HR, 2.36; 95% CI, 1.17-5.03; P = .022), or disease relapse/progression within 24 months of diagnosis (HR, 3.81; 95% CI, 1.73-8.85; P = .001). Additionally, receiving venetoclax in combination with other agents correlated with longer OS (HR, 0.32; 95% CI, 0.14-0.70; P = .007).

Despite 61% of patients being at a low risk for tumor lysis syndrome, 12.3% developed laboratory and 3.7% developed clinical tumor lysis syndrome despite mitigation strategies; this included treatment with allopurinol (90%) and/or intravenous fluids (67%).

Reference

Sawalha Y, Goyal S, Switchenko JM, et al. A Multicenter Analysis of the Outcomes with Venetoclax in Patients with Relapsed Mantle Cell Lymphoma. Blood Adv. Published online February 21, 2023. doi:10.1182/bloodadvances.2022008916