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Tisagenlecleucel yields durable responses in DLBCL

Audrey Abella
27 Jun 2018
Dr Peter Borchmann discusses updates on the JULIET trial.

The second-generation chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (CTL019) continues to drive durable responses in pretreated patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated results from the JULIET* trial presented at EHA 2018.

With a longer median follow-up of 14 months, the best overall response rate (ORR) was 52 percent, with a complete response (CR) rate of 40 percent. “[These findings suggest that] prolonged durable responses can be achieved [with CTL019],” said Dr Peter Borchmann from the University Hospital of Cologne in Cologne, Germany. [EHA 2018, abstract S799]

The 12-month relapse-free survival rate was 65 percent and 78.5 percent among all responders and those with CR, respectively. Furthermore, 54 percent of those who initially had a partial response (PR) converted to CR 9–12 months after the initial response. “[The CTL019] transgene was detected in peripheral blood for up to 2 years in responders,” said Borchmann.

Although median progression-free survival (PFS) for patients with CR had not been reached at 12 months, 83 percent of patients with CR/PR at 3 months remained progression-free.

“Response status at 3 months is already an indicator for durable clinical benefit,” Borchmann pointed out. “[If] patients maintain any kind of remission after 3 months … [as evidenced by the] patients converting from PR to CR over time, PFS will be very similar in PR/CR patients.”

Furthermore, the overall survival (OS) rates at 12 months (49 percent and 95 percent in all and in CR patients, respectively) reflect high remission rates and translate to good survival outcomes, added Borchmann.

 

Manageable safety profile
Nearly 60 percent of patients had all-grade cytokine release syndrome (CRS), 15 percent of whom received tocilizumab and 11 percent received corticosteroids for CRS management.

However, these results should not be compared with findings from previous trials, noted Borchmann. “[We used] a different grading system – the Penn system – which tends to have more severe CRS based on vasopressors. More importantly, the use of tocilizumab in our trial was later than in other trials, which may contribute to the low number of patients being treated.”

All-grade neurologic events occurred in 21 percent, the most common being confusional state and encephalopathy (any grade, 8 percent and 6 percent, respectively).

Despite these adverse events, they were effectively managed, and no deaths were attributed to CTL019 use, CRS, or cerebral oedema, noted Borchmann.

 

Potential allotransplant replacement
Of the 111 participants who received a single-dose infusion of CTL019, 76 percent had stage III/IV disease and more than half (55 percent) were refractory to the last treatment they received.

Second-line failure is quite a ‘desperate’ situation as it denotes a poor prognosis, said Borchmann, taking into consideration the very aggressive nature of second-line treatment (high-dose chemo followed by autologous stem cell transplant). [J Am Soc Hematol Educ Book 2011;1:498-505]

“[M]ost patients are too old or frail, or are suffering from comorbidities … [hence the] very low response rates to conventional approaches and extremely poor OS,” he said. The fraction of patients who needed bridging and lymphodepleting chemotherapy (92 percent and 93 percent, respectively) further highlights the aggressive nature of the underlying disease, he added.

Therefore, the findings address the high unmet medical need for this difficult-to-treat patient population, said Borchmann. “Patients failing two prior lines will not respond to conventional chemotherapy … and allotransplant … might not be very helpful,” he said. “[Our results suggest that] treatment with CTL019 [could] replace allotransplant [and offer meaningful benefit] in this setting.”

“However, we still do not know if these responses are truly long-lasting,” he continued. “[Although the follow-up results] look good with a stable plateau … we have to wait longer. If we find an OS rate in a similar range at 5 years, certainly this will replace allotransplant, but this will take a while from now.”

 

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Most Read Articles
22 Nov 2020
Mental health comorbidities are common among patients with type 2 diabetes mellitus and may lead to worse outcomes, a recent study has found.
Roshini Claire Anthony, 13 Nov 2020

Diabetes is a key risk factor for heart failure (HF), which is the leading cause of hospitalization in patients with or without diabetes. SGLT-2* inhibitors (SGLT-2is) have been shown to reduce the risk of hospitalization for HF (HHF) regardless of the presence or absence of diabetes.

4 days ago
Vitamin D deficiency may be a contributing factor to the mortality rate among patients with the novel coronavirus disease (COVID-19), reports a new study.
Pearl Toh, 3 days ago
Inhaled corticosteroid (ICS) should be the mainstay of long-term asthma management — such is the key message of the latest Singapore ACE* Clinical Guidance (ACG) for asthma, released in October 2020.