Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia: Results of a pooled analysis

Abstract

Background Blinatumomab is a BiTE® immuno‐oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL). AimsTo assess the efficacy and safety of blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & MethodsPatient‐level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). ResultsCompared with patients who received blinatumomab as second or later salvage, those who received blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26–1.97; P < .001) and relapse‐free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98–1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41–0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. DiscussionIn this pooled analysis, the logistic regression analyses indicated greater benefit with blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. ConclusionOverall, blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage.

Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice: results from the NEUF study

“…The NEUF study describes the largest documented European cohort of patients treated with blinatumomab in real-world clinical practice reported to date. The real-world effectiveness of blinatumomab in adults with MRD+ or R/R ALL was comparable to that reported in other clinical and real-world studies [2,3,6,[9][10][11][12][13][14][15].…”

“…In a Phase 3 trial, treatment with blinatumomab resulted in longer median OS than standard chemotherapy [ 9 ]. MRD results were also analyzed in this patient population and showed longer OS for MRD responders than for MRD nonresponders; the difference was greater in first salvage than in second or later salvage [ 10 , 11 ]. In a Phase 2 trial in patients with R/R Ph+ B-cell ALL, 36% of patients achieved complete remission (CR), of whom 88% attained MRD negativity [ 12 ].…”

Outcomes of relapsed B-cell acute lymphoblastic leukemia after sequential treatment with blinatumomab and inotuzumab

“…The current study describes the characteristics and outcomes of patients with R/R B-ALL who received both blinatumomab and inotuzumab for relapsed disease, including a subset of patients who had alloHSCT after both mAbs. The majority of patients in our cohort received blinatumomab as the first mAb, with response rates comparable to those published previously, 14 and inotuzumab was used as the next immediate salvage therapy in 50% of the patients who relapsed after blinatumomab. We found that inotuzumab was effective in inducing CR in 68% of the patients who relapsed after blinatumomab regardless of CD19 expression status.…”

Adverse events of monoclonal antibodies use in therapy of hematological malignancies

“…Nevertheless, blinatumomab has been associated with catheter-related bloodstream infections, therefore patients receiving the drug should be carefully monitored for signs and symptoms of infection. Moreover, CRS, infections and febrile neutropenia were more common AEs of blinatumomab administered in second or later line of treatment compared to patients treated previously, while neurological toxic effects and neutropenia were more frequent during first-line treatment [19]. Also, serious AEs and treatmentrelated fatal events were more frequently reported in the group receiving blinatumomab as a second or subsequent line of therapy.…”

“…Prophylactic management include dose modification, discontinuation of blinatumomab treatment, cytoreduction, and dexamethasone. Additionally, intravenous fluids and tocilizumab, an IL-6 inhibitor, can be used [19]. If grade 3 CRS is diagnosed, blinatumomab treatment may be resumed after discontinuation and administration of dexamethasone.…”