Wang Highlights Encouraging CAR T-Cell Activity in MCL

Michael Wang, MD

The multicenter phase II ZUMA-2 trial investigating the CAR T-cell therapy KTE-X19 in relapsed/refractory mantle cell lymphoma (MCL) reported significant and durable responses, thus paving the way for the novel treatment to revolutionize the field, said Michael Wang, MD. 

"MCL is a deadly disease; it is rare,” said Wang. “Community oncologists may only see 1 or 2 patients with MCL during the time they are practicing. Therefore, less research is being done for it. Targeted therapies are wonderful, and now, they are exploding in terms of combinations, newer generation of agents, and newer targets. "

In December 2019, a biologics license application was submitted to the FDA based on the results from the phase II ZUMA-2 trial, which were presented at the 2019 ASH Annual Meeting.¹

At a median follow-up of 12.3 months, results of the trial demonstrated an overall response rate (ORR) of 93%, with a complete response (CR) rate of 67% for patients with relapsed/refractory MCL after a single infusion of KTE-X19.²

"This is an ongoing study, so we will have longer follow-ups as more time elapses," said Wang. "I'm sure some of the patients will stay in remission for a long time, as other CAR T-cell therapies have demonstrated in other diseases."

In an interview with  OncLive  during the 2019 ASH Annual Meeting, Wang, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discussed the ZUMA-2 trial and the potential impact of CAR T-cell therapy on MCL.

OncLive:  What was the rationale for the ZUMA-2 trial?

Wang:  MCL is a rare subtype of lymphoma. Therefore, it is very difficult to “get good” at treating these patients. The other issue is that MCL has been regarded as one of the most difficult-to-treat lymphomas. The prognosis is bad, and [available treatments] are not curative. 

However, this is changing very rapidly because therapy for patients with MCL has migrated from chemotherapy to chemotherapy-free agents, such as ibrutinib (Imbruvica) and acalabrutinib (Tecentriq). These are both oral agents [that can elicit better responses] than 5 chemotherapies put together. Plus, the patient doesn't lose their hair, they don't need a central line, their blood count levels don't drop, and the infection rate is much better. 

What makes CAR T-cell therapy unique for this population?

A fraction of MCL is so malignant that it can progress through all the chemotherapies and all the targeted therapies you throw at it. 

That is why we are exploring CAR T-cell therapies—to offer a different way to attack this disease. Many studies have shown CAR T-cell therapy is effective for very aggressive leukemias, such as acute lymphoblastic leukemia and large cell lymphoma. 

What were the findings of the ZUMA-2 trial?

We only reported on the first 28 patients out of 60 patients total. Even with that small number of patients, the ORR was over 80%; the CR rate was 53%. These patients are very heavily pretreated who have nearly exhausted all existing therapies. [To see] a very high response rate is exciting. Furthermore, the responses are very durable—sometimes lasting many months.

What does the future look like in this space?

We now have chemotherapy, targeted therapies, and cellular therapies. 

I am the co-leader of The University of Texas MD Anderson B-Cell Lymphoma Moon Shot program, which is a gigantic program with targeted therapies, cellular therapies, immunotherapies, and epigenetic therapies. This program is moving toward precision medicine, which may be [important to combat] resistance to chemotherapy, targeted therapies, and cellular therapies. No one therapy [alone] can cure one disease. 

What approaches should be looked at in patients who become resistant to cellular therapies?

We are able to target, sequence, and biologically study [a patient] to decipher what the key driver is—even one that leads to the resistance in each patient. We can attack the Achilles heel of a particularly patient's resistance mechanisms. 

After cellular therapy, precision medicine, depending on biology, is coming. It has never been a better time to be an MCL doctor. My American dream is to cure as many patients with MCL as possible. 

References

1. Kite submits biologics license application to U.S. Food and Drug Administration for company’s second CAR T cell therapy [news release]. Gilead. Published December 11, 2019. https://bit.ly/34dVgMj. Accessed December 11, 2019.   
2. Wang ML, Munoz J, Goy A, et al. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in patients (Pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL): results of the phase 2 ZUMA-2 study. Presented at: 2019 ASH Annual Meeting; December 7-10, 2019; Orlando, FL. Abstract 754.