ASCO Honolulu: Dr Boddy Discusses the SYMPATICO Study in TP53 Mutant Mantle Cell Lymphoma
Presented by:
Craig Boddy, MD, Hawai’i Pacific Health
Meeting:
ASCO Direct Honolulu, 2024
The Bottom Line
Patients with mantle cell lymphoma (MCL) who have a mutation in the TP53 gene have poor responses to standard therapies and frequent early progression of their disease. Results from the SYMPATICO study suggest that the use of 2 different classes of drugs in combination, ibrutinib (a BTK inhibitor) and venetoclax (a BCL-2 inhibitor), was an effective option for inducing complete responses and durable remissions, specifically in patients with MCL and TP53 mutation.
Background:
Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin’s lymphoma (NHL) which can be associated with an aggressive clinical course and a poor prognosis. About 15 to 20% of patients with MCL also have mutations in the TP53 gene (mTP53) and such patients are considered a more difficult to treat patient population. Patients with mTP53 MCL are more prone to early progression of their disease, and have a poor response to standard of care therapies such as chemoimmunotherapy. The SYMPATICO study examined the efficacy of 2 different classes of drugs for MCL used in combination: the Bruton’s tyrosine kinase (BTK) inhibitor drug ibrutinib, and a BCL-2 inhibitor type drug, venetoclax.
Trial Design and Patients:
SYMPATICO was designed to evaluate the efficacy and safety of the ibrutinib/venetoclax combination for patients with MCL. The current analysis examined outcomes from a pooled cohort of patients with MCL and mTP53 who were treated with the ibrutinib/venetoclax combination. Patients had either relapsed or refractory (R/R) MCL or were treated in the first line (1L) setting with the combination therapy.
Main Trial Results:
The results showed high rates of complete responses (CR) for patients with R/R MCL (58%) and those treated in the 1L setting (55%) for patients receiving the ibrutinib/venetoclax combination. There were also high overall response rates (which includes CR, partial responses and stable disease) for patients in the R/R (80%) and 1L groups (90%) treated with the combination therapy. Results from the trial also showed a median progression free survival (PFS) of 20.9 months, and a median overall survival (OS) of 47.1 months for the total pooled population of MCL mTP53 patients receiving the combination therapy. Additional results from the trial showed a benefit of the combination ibrutinib/venetoclax therapy as compared to ibrutinib alone for both PFS and OS in R/R MCL patients with mTP53. As expected, those patients without TP53 mutations had better PFS and OS outcomes relative to those with mTP53 R/R MCL, and those patients treated with the combination had better outcomes as compared with ibrutinib alone. Safety results in the mTP53 MCL population of patients were overall similar with those seen in the total trial population, and consistent with the known safety profile for each agent individually.
Conclusions and Faculty Insights:
Dr Boddy noted that SYMPATICO was, to date, the largest single cohort study of patients with mTP53 MCL. The combination of ibrutinib and venetoclax used in the study was associated with promising efficacy, high CR rates, and durable remissions in this more difficult to treat patient population. In addition, Dr Boddy noted there were no new safety signals and no unexpected toxicities with the combination. Overall, Dr Boddy thought the results are encouraging in view of the otherwise poor responses and shorter survival outcomes observed with standard chemoimmunotherapy in patients with mTP53 MCL.
Speaker Disclosure Information:
Dr Boddy reported no relevant disclosures for this presentation.