Blinatumomab as salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma may induce durable complete responses and a survival benefit, according to a pooled analysis of 3 clinical trials.
Blinatumomab (Blincyto) as salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) may induce durable complete responses (CRs) and a survival benefit, according to a pooled analysis of 3 clinical trials.
Patients with relapsed/refractory DLBCL are associated with a poor prognosis, in which 50% to 74% of patients fail to achieve a response to their next line of therapy. The median overall survival (OS) is expected to be 6 to 10 months. Among those who achieve disease remission with salvage therapies, 30% to 50% of patients will relapse within 1 year of treatment. This underscores the importance of developing salvage therapies that can induce more durable responses.
The 3 studies used for the pooled analysis were open-label, multicenter, single-arm clinical trials, including the phase 1 study of relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL; NCT00274742; n = 14), the phase 2 of relapsed/refractory DLBCL (NCT01741792; n = 25), and the phase 2 of relapsed/refractory B-NHL (NCT02910063; n = 34). According to the findings from the phase 1 of B-NHL and phase 2 trials of DLBCL and B-NHL, blinatumomab generated activity in patients with relapsed/refractory DLBCL, in which the CR rates were 26%, 16%, and 29%, respectively. The duration of CR, OS, and safety of the CD19/CD3 bispecific T-cell engager (BiTE) were evaluated.
The objective response rate (ORR) was an end point for both the phase 1 study of B-NHL and the phase 2 of DLBCL, while complete metabolic response (CMR) was the primary end point for the phase 2 B-NHL study. Overall, 17 of the 73 patients (23%) in the pooled analysis achieved a CMR or CR within 12 weeks of treatment with blinatumomab and were included in the assessment of duration of CR (DOCR).
Overall, 83% of patients in the phase 2 -B-NHL study and 100% of those in the phase 2 DLBCL study had DLBCL, while 68% in the phase 1 had DLBCL. A total of 11 patients (65%) had relapsed disease, 6 (35%) had primary refractory disease, 16 (94%) had at least 2 lines of prior therapy, and 4 (24%) had received prior hematopoietic stem cell transplantation (HSCT).
Sixteen of the 17 patients with relapsed/refractory DLBCL who achieved a CR/CMR had completed 1 cycle of blinatumomab and 11 had received at least 80% of their total intended dose for cycle 1. Sixteen patients (94%) had treatment interruptions, which was due to adverse events (AEs) in 5 patients (29%). Three patients who had completed cycle 1 of blinatumomab were able to complete cycle 2, and 2 patients achieved at least 80% of cycle 2’s intended dose. During cycle 2, treatment discontinuation was due to an AE in 2 patients (12%) and technical reasons in 1 patient.
The median DOCR had not been reached (95% CI, 6.0-not estimable [NE]) after a median follow-up of 15.6 months. Overall, 79.0% of patients remained in response at 6 months, 62.2% at 12 months, 62.2% at 18 months, and 62.2% at 21 months. Among 17 patients who had achieved a CR/CMR, 4 (23.5%) had relapsed while 1 (5.9%) had died during follow-up. Three patients of the 7 who were still in CR at 12 months received an autologous HSCT.
Thirteen patients had achieved a partial response (PR), and the median duration of a PR was 2.1 months (95% CI, 0.9-NE) after a median follow-up of 7.6 months. Additionally, 32.7% were estimated to remain in response at 6 months, 21.8% at 12 months, 21.8% at 18 months, and NE at 24 months. Six of the 13 patients (46.2%) relapsed, 2 (15.4%) had died, and 4 (30.8%) received an HSCT.
The median OS was not reached after a median follow-up of 16.4 months (95% CI, 13.1-NE) The OS probability was 100% at 6 months, 86.5% at 12 months, 77.9% at 18 months, and 77.9% at 24 months.
Three of the 17 patients who responded after treatment (17.6%) died during follow-up and 9 (52.9%) went on to receive HSCT.
All 17 patients had experienced any-grade treatment-emergent AEs (TEAEs), 14 (82.4%) of which experienced grade 3 or greater TEAEs and 8 (47.1%) of which had serious AEs. Three patients (17.6%) discontinued treatment due to TEAEs. The most common grade 3 TEAEs included neurologic events (5.3%), infections (35.3%), cytopenias (29.4%), and elevated liver enzymes (17.6%).
Treatment-related AEs (TRAEs) occurred in 16 patients (94.1%), and 11 patients (64.7%) had grade 3 or greater TRAEs, 1 (5.9%) of which experienced grade 4 or greater TRAEs. Four of the TRAEs were considered serious. Eleven patients (64.7%) developed TRAEs of grade 3 or greater in severity, and 2 patients (11.8%) discontinued treatment. However, no life-threatening or fatal AEs were observed.
Out of the 17 patients, 15 (88.2%) had neurologic AEs of any grade, which included tremor (52.9%), headache (47.1%), and paresthesia (23.5%). Neurologic AEs of grade 3 or greater in severity were observed in 6 patients (35.3%), which led to treatment interruptions in 4 patients (23.5%) and treatment discontinuation in 2 patients (11.8%). No grade 4 or fatal neurologic AEs were observed, but 1 patient experienced grade 3 cytokine release syndrome.
Despite the median DOCR and OS not being reached at the time of analysis, a total of 62.2% of patients were responding, and 86.5% were alive at 12 months of follow-up. Three patients in the phase 2 DLBCL trial also achieved late CRs that were not included in this analysis, and those patients also had longer DOCRs.
Viardot A, Hess G, Bargou RC, et al. Durability of complete response after blinatumomab therapy for relapsed/refractory diffuse large B-cell lymphoma. Leukemia & Lymphoma. [Published Online July 7, 2020]. doi: 10.1080/10428194.2020.1783442