Ibrutinib Plus Venetoclax Demonstrates Efficacy, Safety for TP53-Mutated Mantle Cell Lymphoma Treatment

Results from the SYMPATICO study

Michael Wang, MD, MD Anderson Cancer Center at the University of Texas, Houston, Texas, presents data on the efficacy and safety of ibrutinib plus venetoclax treatment for patients with high-risk TP53-mutated mantle cell lymphoma (MCL).

This research was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

Good day everybody. My name is Michael Wang. I'm a professor at the MD Anderson Cancer Center in Lymphoma Service. At this ASCO 2024 it is my great pleasure to present the SYMPATICO study population in patients with [mantle cell lymphoma] with TP53 mutations.

As we all know, on behalf of my colleagues, I presented the primary data of SYMPATICO last ASH 2023. That presentation showed that the combination of ibrutinib and venetoclax class was very effective in treating relapsed mantle cell lymphoma compared with ibrutinib with a placebo arm. The PSS was statistically significant and there was a trend for overall survival benefit.

At ASCO 2024, I'm presenting the SYMPATICO study but only the TP53 mutated patients. As we all know, TP53 mutation is the number 1 worst factor in mantle cell lymphoma. For mantle cell lymphoma patients, it's public enemy number one. So, very few studies report TP53 mutated patients, or they do with the very small numbers.

This time in the history of the mantle cell lymphoma, we put the largest [number] of TP53 mutated patients from the SYMPATICO population. We had 3 cohorts: the part 1 cohort, the relapsed setting, and the randomized, relapsed setting that have 45 patients with TP53 mutations. Then we had 29 patients with the mutation treated at the frontline. If you combine all of them all of them we had 74 patients. This is the largest the population of TP53 mutated patients in the literature of mantle cell lymphoma.

We showed the overall response rate for the relapsed setting was 80% to 85%. However, for the first-line treated patient, the overall response was higher at 90%. However, the CR are both very high, in the relapsed setting and the frontline setting. They are ranging from 45% to 48%. Those are numbers with the TP53 mutation. Furthermore, the PFS was very significant, prolonged in 74 patients with a median PFS of 20.9 months. This is, again, very significant. We have compared and we have considered our data in the historical context.

The overall survival was 47 months for all 74 patients. Imagine in the past literature, if the TP53 was mutated, [patients] only live about 1 to 2 years, usually about 1.5 years. Now with the 2 oral drugs, ibrutinib and venetoclax, we were able to achieve overall survival of 47 months, almost 4 years. This is really remarkable. And I think the combination of ibrutinib, and venetoclax are really good for the TP53 mutated patients.

I have to point it out that the combinations, although they significantly improved overall response rate and prolonged PFS and overall survival, however, so far cannot totally overcome the TP53 mutation, because we also compared the TP53 mutation with the unmutated patients, and still the unmutated patients did much better. Thank you for this interview.

Source:

Wang M, Jurczak W, Trneny M, et al. Efficacy and safety of ibrutinib plus venetoclax in patients with mantle cell lymphoma (MCL) and TP53 mutations in the SYMPATICO study. Presented at the ASCO Annual Meeting. May 31–June 4, 2024; Chicago, IL. Abstract 7007