Updates from the annual ASH meeting, December 2018.
At the 60th American Society of Hematology’s Annual Meeting & Exposition in San Diego, California, held December 1-4, 2018, researchers presented data from an ongoing randomized, double-blind trial comparing the efficacy of CT-P10 (Truxima)—a newly approved rituximab biosimilar— with reference rituximab (Rituxan) in patients with previously untreated advanced follicular lymphoma.
The study enrolled 140 patients, 124 patients of whom completed the full 8 cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CVP) induction therapy.1 In total, 122 patients who showed response during the induction period (62 patients in the CT-P10 treatment arm and 60 patients in the reference arm) then moved on to the maintenance period, during which 12 cycles of rituximab monotherapy were administered at intervals of 2 months.
Efficacy was determined based on outcomes including progression-free survival, duration of response, and overall survival (OS). The updated safety profile of CT-P10 compared with reference rituximab in advanced follicular lymphoma was also assessed. The study was designed to continue until death or up to 3 years from the randomized date of the last patient.
At the time of the cutoff date, the median follow-up was 23 months (range, 0.5-34) in the CT-P10 group and 22 months (range, 0.2-33) in the reference rituximab group. The rates of relapse, disease progression, or death from any cause were 22.9% and 24.3% for the CT-P10 and reference rituximab groups, respectively.
As for sustained response, the proportion of patients who showed relapse or disease progression after previously achieving overall response was 19.4% in the CT-P10 arm and 21.3% in the reference arm. Notably, there was no statistically significant difference in OS between either group with a 2-year OS of 93.2% for CT-P10 patients and 95.3% in reference rituximab patients.
Furthermore, “The updated safety results did not reveal any new trends or new signals noted in the patients treated with CT-P10,” a Celltrion representative said in an email.
The study’s authors concluded that, at the median follow-up of 23 months, the data demonstrated comparable progression-free survival, sustained response, and OS between both the biosimilar and the reference product.
FDA approved CT-P10 on November 28, 2018, under the brand name Truxima, though a launch date has yet to be disclosed.2 “Celltrion and Teva Pharmaceutical Industries entered into an exclusive partnership in October 2016 to commercialize Truxima in the United States and Canada. Teva and Celltrion have reached a settlement agreement with Genentech, including entry terms. The terms and conditions of that agreement are confidential at this time,” noted Woosung Kee, CEO of Celltrion.
Surabhi Dangi-Garimella, PhD
A median 19-month follow-up of the JULIET trial—a single-arm, open-label, multicenter, global, pivotal phase 2 trial of the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel directed against CD19-expressing B cells—has found a 40% complete response (CR) and a manageable safety profile in adult patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).1
Tisagenlecleucel (Kymriah) was FDA approved in May 2018 for the treatment of adult patients with R/R large B-cell lymphoma following at least 2 prior line of therapy.
Conducted across 27 sites in 10 countries, the JULIET trial enrolled 167 patients with R/R DLBCL at the cutoff date of May 21, 2018, and 115 of them received an infusion of CD19-directed CAR T cells (dose range 0.1 x 108 to 6 x 108 cells). Eligibility criteria included at least 18 years of age; at least 2 lines of prior therapy, including an anti-CD20 antibody and an anthracycline; and were ineligible for or had failed autologous stem cell transplant (ASCT). Primary trial endpoint was overall response rate (ORR), as a sum total of the CR and partial response as assessed by an independent review committee. Secondary endpoints included duration of response (DOR), overall survival (OS), and safety.
About 90% of infused patients received bridging therapy and 93% received lymphodepleting chemotherapy. Median time from infusion to data cutoff was 19.3 months. Median age was 56 years (range, 22-76 years); 23% were aged ≥65 years. At study entry, 77% of infused patients had stage III/ IV disease; 55% and 43% had germinal center and activated B-cell molecular subtypes, respectively. More than half of the patients had received at least 3 prior lines of antineoplastic therapy (range, 1-6) and about the same number had undergone a prior ASCT.
Of the 99 patients who were evaluated who had at least 3 months of follow-up, ORR was 54% (95% CI, 43%-64%), with 40% CR. Further, ORR was consistent across prognostic subgroups that were evaluated, including prior ASCT, gender, age, and molecular subtype.
Median DOR was not reached at the time of data analysis, and DOR was not influenced by age or R/R status, the study found. No relapses were observed beyond 11 months after infusion. The median OS for all infused patients was 11.1 months (95% CI, 6.6 months-not evaluable [NE]) and was not reached for patients in CR (95% CI, 21 months-NE). The
OS probability was 48% (95% CI, 38%-57%) at 12 months and 43% (95% CI, 33%-53%) at 18 months, and, similar to DOR, was not influenced by the patient’s age or R/R status.
“These findings are consistent with what we’ve shown in our single-site studies here at Penn, which is that the majority of patients who go into remission stay in remission,” said Stephen J. Schuster, MD, director of the Lymphoma Program at the Abramson Cancer Center of the University of Pennsylvania, who is the principle investigator for the JULIET trial.2
The authors compared the survival curves from their current study with those of the SCHOLAR-1 study3 and the CORAL study,4 and they found that patients enrolled in JULIET performed much better in terms of OS. The OS probability was about 30% and 25% for SCHOLAR-1 and CORAL at 12 months, respectively, and 25% and 20% at 24 months, respectively.
More than half (57%) of patients experienced cytokine release syndrome, 34% of which were grade 3/4. Prolonged (>28 days) cytopenias were observed in 45% patients, 34% of which were high-grade (3/4); a majority (17%) of infections in 37% of patients were grade 3. Twenty percent of treated patients experienced neurological adverse events, including a single case of grade 2 cerebral edema, which was detected without a contrast computed tomography (CT) scan, which disappeared following a contrast CT scan after 24 hours.
The authors report that there were no treatment-related deaths following their last data presentation at the Congress of the European Hematology Association in June 2018.5