Caron Jacobson, MD, a senior physician and medical director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, discusses the high-risk patient population within relapsed/refractory indolent non-Hodgkin lymphoma (iNHL) included in the phase 2 ZUMA-5 study.

Targeting patients with relapsed/refractory iNHL in the third-line setting and beyond tends to draw upon what is observed in a higher-risk patient population, says Jacobson. Many patients with follicular lymphoma will experience multiple-year remissions following their first- or second-line therapy; as such, many of  can be observed for several years. Therefore, accruing patients who already require a third line of therapy means highlighting a higher-risk group of patients to begin with, Jacobson explains.

Early data from the ZUMA-5 study with axicabtagene ciloleucel (axi-cel; Yescarta) examined many patient samples and disease characteristics to evaluate  associations with response and toxicity. Further examination of these factors is required, says Jacobson. However, based on the early data reported, the most important aspects include the efficacy and adverse effect profile of the product, concludes Jacobson.

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Caron Jacobson, MD, discusses the high-risk patient population within relapsed/refractory indolent non-Hodgkin lymphoma included in the phase 2 ZUMA-5 study.

Dr. Jacobson on the ZUMA-5 Trial With Axi-Cel in High-Risk Relapsed/Refractory iNHL 

Caron Jacobson, MD, a senior physician and medical director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute, and an assistant professor of medicine at Harvard Medical School, discusses the interim analysis results of the marginal zone lymphoma (MZL) cohort in the phase 2 ZUMA-5 study with axicabtagene ciloleucel (axi-cel; Yescarta) in relapsed/refractory indolent non-Hodgkin lymphoma.

The MZL cohort included in the efficacy analysis was smaller than the follicular lymphoma cohort, with just 16 patients, says Jacobson. Patients were required to have 1 month of follow-up in order to have at least 1 scan to review for efficacy. The primary end point was response rate by independent radiology review. When the central radiology review examined the pretreatment scans, they found that some of these patients did not meet measurable disease criteria, says Jacobson.

The overall response rate was closer to 81%, with a complete response rate of 75%, adds Jacobson. Moreover, 19% of patients were non-evaluable because they were not felt to have measurable disease prior to receiving CAR T-cell therapy, explains Jacobson.

The data in the MZL cohort looks less favorable than those reported in the follicular lymphoma cohort, mostly because of the fact that 19% of patients were not determined to be evaluable. No patients experienced disease progression in that cohort.

Notably, the follow-up time is very short, says Jacobson. Most patients had a 6-month follow-up, so the duration of response curves were truncated early. The data are immature in terms of durability of response in the MZL cohort, concludes Jacobson.

Caron Jacobson, MD, discusses the interim analysis results of the marginal zone lymphoma cohort in the phase 2 ZUMA-5 study with axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma.

Dr. Jacobson on the Interim Analysis of the MZL Cohort in the ZUMA-5 Trial

Caron Jacobson, MD, medical director of the Immune Effector Cell Therapy Program; a physician at Dana-Farber Cancer Institute; and an assistant professor of medicine at Harvard Medical School, discusses the next steps with axicabtagene ciloleucel (axi-cel; Yescarta) in relapsed/refractory indolent non-Hodgkin lymphoma.

At the 2020 ASCO Virtual Scientific Program, findings from the phase 2 ZUMA-5 study demonstrated a 95% overall response rate with a complete response rate of 81% in patients with relapsed/refractory follicular lymphoma. Additionally, clinical benefit was noted with the CAR T-cell therapy in patients with marginal zone lymphoma (MZL).

The data remain immature, and patients are still enrolling to the MZL cohort, says Jacobson. In the follicular lymphoma cohort, a planned 12-month analysis may shed light on the durability of these responses.

ZUMA-5 is designed to be a pivotal study for axi-cel to receive an expanded indication from the FDA in lymphoma, explains Jacobson.

Moreover, if the durability and safety profile of the agent continue to elicit favorable data, axi-cel or other CAR T-cell therapies may be evaluated in earlier lines of treatment for high-risk patients, including those who progress following initial chemoimmunotherapy, concludes Jacobson.

Caron Jacobson, MD, discusses the next steps with axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma.



Dr. Jacobson on the Next Steps With Axi-Cel in R/R Indolent Non-Hodgkin Lymphoma

Caron Jacobson, MD, medical director of the Immune Effector Cell Therapy Program; a physician at Dana-Farber Cancer Institute; and an assistant professor of medicine at Harvard Medical School, discusses the design of the phase 2 ZUMA-5 trial in patients with relapsed/refractory indolent non-Hodgkin lymphoma.

The ZUMA-5 trial is an open-label, clinical trial that treated every patient with the same therapy, which was axicabtagene ciloleucel (axi-cel; Yescarta), says Jacobson. This study included 2 subtypes of patients with relapsed/refractory indolent B-cell NHL: follicular lymphoma and marginal zone lymphoma (MZL). The planned accrual for the trial was 125 patients with follicular lymphoma and 35 patients with MZL.

 was on all patients with follicular lymphoma, as well as 16 patients with MZL. All of these patients were in the third-line treatment setting or beyond. Prior treatments included chemoimmunotherapy with a CD20 antibody and an alkylating agent. Patients had a median of 3 prior lines of therapy; most patients received the study treatment as their fourth line of treatment, says Jacobson. Approximately 70% of the patient population had 3 or more prior lines of therapy. Thus, ZUMA-5 included a heavily pretreated, high-risk patient population. Most patients had a high tumor bulk per GELF criteria and a high-risk FLIPI score. Additionally, half of all patients enrolled had progressed after first-line therapy within the first 2 years, concludes Jacobson.

Caron Jacobson, MD, discusses the design of the phase 2 ZUMA-5 trial in patients with relapsed/refractory indolent non-Hodgkin lymphoma.


Dr. Jacobson on Design of ZUMA-5 Trial in R/R Indolent Non-Hodgkin Lymphoma

Caron Jacobson, MD, medical director, Immune Effector Cell Therapy Program, and physician, Dana-Farber Cancer Institute, assistant professor of medicine, Harvard Medical School, discusses the benefit of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory follicular lymphoma. 

Interim results from the phase 2 ZUMA-5 trial presented at the 

 showed that the CAR T-cell product induced a high overall response rate of 95% and a complete response (CR) rate of 81% in the cohort of patients with relapsed/refractory follicular lymphoma. The median follow-up was 15.3 months and 68% of patients in this cohort had an ongoing response as of the data cutoff.

These are early data for an indolent disease where it’s understood that patients could relapse many years after therapy; however, the data appear to be very promising and remissions may prove to be durable, concludes Jacobson.

Articles

Caron Jacobson, MD, discusses the benefit of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory follicular lymphoma. 

Dr. Jacobson on the Benefit of Axi-Cel in Relapsed/Refractory Follicular Lymphoma

Caron Jacobson, MD, medical director, Immune Effector Cell Therapy Program, and physician, Dana-Farber Cancer Institute, assistant professor of medicine, Harvard Medical School, discusses the benefit of axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed/refractory follicular lymphoma.

Interim results from the phase 2 ZUMA-5 trial presented at the 

 showed that the CAR T-cell product induced a high overall response rate of 95% and a complete response (CR) rate of 81% in the cohort of patients with relapsed/refractory follicular lymphoma. The median follow-up was 15.3 months and 68% of patients in this cohort had an ongoing response as of the data cutoff.

These are early data for an indolent disease where it’s understood that patients could relapse many years after therapy; however, the data appear to be very promising and remissions may prove to be durable, concludes Jacobson.

Caron Jacobson, MD, discusses the benefit of axicabtagene ciloleucel (Yescarta) in patients with relapsed/refractory follicular lymphoma.

Dr. Jacobson on the Benefit of Axi-Cel in Relapsed/Refractory Follicular Lymphoma  

Caron Jacobson, MD, medical director, Immune Effector Cell Therapy Program, and physician, Dana-Farber Cancer Institute, assistant professor of medicine, Harvard Medical School, discusses the safety profile of axicabtagene ciloleucel (axi-cel; Yescarta) in relapsed/refractory indolent non-Hodgkin lymphoma (iNHL).

An interim analysis of the phase 2 ZUMA-5 trial presented at the 2020 ASCO Virtual Scientific Program showed that axi-cel elicited significant and durable clinical benefit in patients with relapsed/refractory follicular lymphoma and marginal zone lymphoma (MZL).

Axi-cel had a favorable safety profile in the cohort of patients with follicular lymphoma. As such, axi-cel could be considered for outpatient dosing, pending further positive results, says Jacobson.

About 23% of patients with follicular lymphoma did not experience any-grade cytokine release syndrome (CRS) and of those who did, 7% was grade 3 or higher, says Jacobson. Notably, the median time to onset of CRS was around 4 days compared with 2 days in large-cell lymphoma. Additionally, 15% of patients in this cohort experienced grade 3 or higher neurologic toxicities. 

Among patients with MZL, the rates of high-grade CRS and neurologic events were 13% and 38%, respectively, says Jacobson. These findings are in line with what has been observed in large-cell lymphoma.

Caron Jacobson, MD, discusses the safety profile of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma.

Caron Jacobson, MD

Articles

Dr. Jacobson on the ZUMA-5 Trial With Axi-Cel in High-Risk Relapsed/Refractory iNHL

Dr. Jacobson on the Interim Analysis of the MZL Cohort in the ZUMA-5 Trial

Dr. Jacobson on the Next Steps With Axi-Cel in R/R Indolent Non-Hodgkin Lymphoma

Dr. Jacobson on Design of ZUMA-5 Trial in R/R Indolent Non-Hodgkin Lymphoma

Dr. Jacobson on the Benefit of Axi-Cel in Relapsed/Refractory Follicular Lymphoma

Dr. Jacobson on the Benefit of Axi-Cel in Relapsed/Refractory Follicular Lymphoma

Dr. Jacobson on the Safety Profile of Axi-Cel in Relapsed/Refractory Indolent Lymphoma