Ibrutinib Plus Venetoclax Achieve High Response Rates as Frontline Therapy for MCL: SYMPATICO
Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, shares progress in the field of treating mantle cell lymphoma (MCL) and the results of the SYMPATICO trial which evaluated ibrutinib combined with venetoclax among patients with MCL who were treatment-naïve and had a TP53 mutation.
These data were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
The results of this analysis demonstrated efficacy and safety for ibrutinib combined with venetoclax as a first-line treatment for patients who have MCL with a TP53 mutation, and Dr Wang stated, “There's tremendous progress in the process of mantle cell lymphoma treatment.”
Transcript:
Hello, I'm Michael Wang, Puddin Clarke Endowed Professor in the Department of lymphoma and myeloma at MD Anderson Cancer Center in Houston, Texas. I have been enjoying ASCO 2025 here in Chicago and at this meeting I am presenting 2 studies.
The first study is an international, multicenter clinical trial that's called by the name of SYMPATICO. SYMPATICO in Spanish is 'good-looking'. The SYMPATICO study has 2 international cohorts. The first cohort is in mantle cell lymphoma that has relapsed, that means frontline therapy and after a few therapies, the patient's lymphoma relapsed. In that relapsed cohort, I presented earlier in the past year, it showed a dramatic result in favor of the ibrutinib-venetoclax versus ibrutinib plus placebo.
This meeting today, I presented the second cohort, not in the relapsed, but in treatment-naive patients. Basically, based mantle cell lymphoma patients who are newly diagnosed, but have not been treated. In this we enrolled 78 patients in this international cohort. That was 78. We have 2 populations, the first population is the older patients who are 65 or older, and younger patients who are less than 65, but have TP53 mutations.
Overall, the study is a huge success because it met the primary objective. The overall response rate was 95%. You imagine that in a very hard to treat disease among older people using 2 oral therapies, ibrutinib, a BTK oral inhibitor, and venetoclax, also a BCL2 inhibitor. These are both oral drugs and these are outpatient therapy. The combination of these 2 orals induced a response of 95%. 95% means that 95% of the patients in this study have shrunk more than 50%. How about those who shrank 100%? 69% of patients shrunk 100%, with a CR rate of 69%.
This is very, very amazing data, overall response rate by 2 oral therapies. Not only are the responses high, but it is also durable. After a 40.5 months follow-up, 3 and a half years follow-up, the median progression-free survival (PFS) is at 42.2 months. The overall survival has not even been reached, so this is a very significant study. It should be new combination, as a new option for the older patients who are newly diagnosed with the mantle cell lymphoma.
The cohort with the TP53 mutation also performed relatively well, although it is not as good as those without TP53 mutation. Even those with TP53 mutation, the median PFS was 22 months. Still very good.
This is the first study of a chemo-free 2 target agents as oral and imagine in the recent past, we have admit the patient to the hospital, put a big catheter in them and give them 5 drug chemotherapies like R-DHAP, R-MINE, ICE therapy. Those patients lose their hair, they have decreased blood counts, and they have big clusters, when the blood counts are low, they need a blood transfusion, platelet transfusions, and they sometimes use infection control. Imagine that, and now we are using 2 oral agents. We can achieve a higher response than the 5-drug chemotherapy.
There's tremendous progress in the process of mantle cell lymphoma treatment. The second project that I'm going to present is the Bantam clinical trial, which is an endoplasmic reticulum (ER) stress clinical drug as oral therapy and it is first in human and it's very promising. I'm looking forward to enrolling the first patient.
Many people ask me, Dr. Wang, when are we going to cure mantle cell lymphoma? Remember, in the recent past, that mantle cell lymphoma was the worst lymphoma to have—hard to treat, came back all the time, kills the patients all the time. I think we are in the actual process of curing people. My definition for curing mantle cell lymphoma is complete remission for 15 years without interruption. Many of my patients in my clinic already exceeded 12 years, so I'll wait for 3 years so I can call them cured. But I think they're cured.
Therefore, it is not only me, but in the whole field with everybody, collaboration, multi centers, and all the colleagues—not only in the US but globally—and with the government support, industry support, science support, and patients and family support, we are close to curing the disease. Thank you very much.
Source:
Wang M, Hoffmann M, Wrobel T, et al. Efficacy and safety of first-line ibrutinib plus venetoclax in patients with mantle cell lymphoma (MCL) who were older or had TP53 mutations in the SYMPATICO study. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 7017.
