CAR T-Cell Therapy Continues to Generate Positive Results in Hematologic Cancers

Ankit Kansagra, MD

Positive data continue to be demonstrated with investigational CAR T-cell therapies in hematologic malignancies, specifically in multiple myeloma, explained Ankit Kansagra, MD.

For example, results of the phase Ib/II CARTITUDE-1 trial showed that the BCMA-directed CAR T-cell therapy JNJ-4528 achieved a 100% overall response rate (ORR) with early and deep responses in 29 patients with heavily pretreated relapsed/refractory myeloma at a median follow-up of 6 months. The ORR consisted of a 66% stringent complete response (CR) rate, a 3% CR rate, a 17% very good partial response (PR) rate, and a 14% PR rate.

Additionally, the median time to first response and the median time to ≥CR were 1 month each. All but 2 patients were progression free at 6 months, and all 17 patients who were evaluable for minimal residual disease (MRD) had MRD negativity. Based on these data, the FDA granted JNJ-4528 a breakthrough therapy designation for the treatment of patients with relapsed/refractory multiple myeloma.

“CAR T-cell therapy in myeloma is a hugely expanding field. There are some new CAR T-cell therapies coming in the pipeline,” said Kansagra. “CAR T-cell therapy for lymphoma has been out for about 2 years and now has real-world data, which is the most important part of trying to understand how [CAR T-cell therapy] is going to impact patients.”

In an interview during the 2020 OncLive^® State of Science Summit™ on Hematologic Malignancies, Kansagra, an assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center of The University of Texas Southwestern Medical Center, discussed the evolving use of CAR T-cell therapy in multiple myeloma and lymphoma.

OncLive: What is the current state of CAR T-cell therapy?

Kansagra: We are in the infancy of CAR T-cell therapy. Right now, most of the CAR T-cell therapies, which are used in clinical trials, are the second generation of CAR T-cell therapy. You know that the [second generation of therapies] have to be better than what [the first-generation treatments] were. This is a proof of concept; [CAR T-cell] therapy works.

We need to figure out how to make [CAR T-cell therapy] better, how to find the right type of construct, how to find the right patient population, where to use it, and how to help those patients who relapse [on CAR T-cell therapy]. There are more unanswered questions, but this is a breakthrough therapy. We must make the most of the experience we have had for the past 3 years.

What are some of the CAR T-cell therapy updates in multiple myeloma?

The major update was the CARTITUDE-1 study. This study used the LEGEND-2 compound that was initially tested in China. That compound has been used in about 30 patients in the United States in a phase I clinical trial. The therapy was shown to be effective in 9 of 10 patients, translating to be 90% effective.

[We have also seen data with] the CAR T-cell therapy bb2121 [idecabtagene vicleucel]. This is, to some extent, a similar product. This [bb2121] therapy could potentially be given in an outpatient setting, depending on the cytokine release syndrome (CRS) or the toxicity that occurred.

Additionally, even with a lower dose, we are seeing a good efficacy with this therapy. It is hard to compare 2 different products, but we are seeing how this construct was made. We might be able to get very good efficacy as it [is explored further] in trials.

What are there the updates with CAR T-cell therapy in lymphoma?

There were a lot of fantastic updates with real-world evidence. One product called axicabtagene ciloleucel (axi-cel; Yescarta), which has been out for about 2 years now, has treated more than 500 patients countrywide in more than 50 institutions; [these patients] were monitored by the Center for International Blood and Marrow Transplant Research (CIBMTR). They noticed that this therapy is very efficacious, which was the most important part. Sometimes, [the drug appears efficacious] in clinical trials but that isn't replicated in the real world. The toxicity or safety profile [in the real-world setting] was very similar to what we saw in clinical trials.

The use of medications to prevent or treat CRS or other toxicities was more [in the real-world setting] than what we have seen in clinical trials. Medications, such as steroids and or tocilizumab (Actemra), which is a common medication to treat CRS, were used a lot more in the real-world setting than in clinical trials.

What is the future of CAR T-cell therapy? Does it involve combinations?

In myeloma, we have learned that CAR T-cell therapies are very efficacious. We can combine many compounds with [CAR T-cell therapy], which can potentiate the efficacy of T-cell therapy. Many [combinations with CAR T-cell therapy] are preclinical models, mouse models, or not-in-human studies, which might replicate into clinical trials. Many future trials are planning to give [CAR T-cell] therapies in earlier lines of treatment, not after failing 5, 6, or 7 different therapies. Rather, [CAR T-cell therapy will be given] after 2 or 3 lines of therapy and even in patients with newly diagnosed [disease].

Another future development in myeloma will be treatment options for patients who relapse after CAR T-cell therapy. What would be the safest options for those situations?

What advice can you provide for practicing oncologists who do not have experience with CAR T-cell therapy?

This is a rapidly changing landscape. We are using these [CAR T-cell] therapies in lymphoma as a commercial product in the third-line setting. It is coming up in the second-line setting, which means that somebody [must] compare [CAR T-cell therapy] with autologous stem cell transplant. CAR T-cell therapy is also expanding quickly in the myeloma landscape.

If you have a patient who you think is eligible for [CAR T-cell therapy], reach out to your colleague who does administer CAR T-cell therapy and ask them whether they have not just a commercial product but a clinical trial [to enroll your patients on].

Additionally, if you are interested in starting CAR T-cell therapy, that is excellent because we need to improve access to these therapies for patients. [CAR T-cell therapy centers can be created] through the National Marrow Donor Program and CIBMTR. They have very finely laid guidelines on how to start the center from scratch.

Madduri D, Usmani SZ, Jagannath S, et al. Results from CARTITUDE-1: a phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against B-cell maturation antigen (BCMA), in patients with relapsed and/or refractory multiple myeloma (R/R MM). Blood. 2019;134(suppl 1):577. doi: 10.1182/blood-2019-121731.