Sequencing of novel agents in relapsed/refractory B‐cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia

Abstract

Background The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B‐cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity. Methods In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared. Results Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety‐two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09). Conclusions Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.

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

“…Lastly, because most patients in our study received blinatumomab as the mAb1 followed by inotuzumab as the mAb2, the response pattern and toxicity profile after mAb2 in our cohort could be more representative of an effect of inotuzumab. The recent retrospective study by Badar et al 7 reported efficacy and toxicity of blinatumomab and/or inotuzumab in patients with R/R B-ALL. The study included a subset of 61 patients who received both mAbs (n = 40, blinatumomab as mAb1; n = 21, inotuzumab as mAb1), but the analysis focused mainly on response duration and survival as related to the mAb sequence administered.…”

“…The majority of published clinical data of blinatumomab and inotuzumab are from clinical trials that predominantly reported initial responses to either of these agents only, whereas clinical course and outcomes of patients who received both mAbs have not been well-described. Limited data is available on whether patients who relapse after blinatumomab or inotuzumab derive any therapeutic benefit to the alternate mAb (7). Moreover, clinical benefit and safety of alloHCT after both blinatumomab and inotuzumab in these heavily-treated patients are unclear.…”

“…Limited data are available on whether patients who relapse after blinatumomab or inotuzumab derive any therapeutic benefit to the alternate mAb. 7 Moreover, the clinical benefit and safety of alloHSCT after both blinatumomab and inotuzumab in these heavily treated patients are unclear.…”

Time to First Subsequent Salvage Therapy in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia Treated With Inotuzumab Ozogamicin in the Phase III INO-VATE Trial

“…15 Among patients who relapsed following InO treatment, those who subsequently received blinatumomab achieved a remission rate of 52%. 16 Although data are limited on CAR Tcell therapy following InO, an individual case report has shown promising results. 17 With the increasing availability of novel agents, the importance of intermediate clinical trial endpoints such as TST may also increase, and alternative parameters to OS may increasingly be considered in assessing treatment value and degree of clinical benefit.…”

Baseline cluster of differentiation 22 fluorescent intensity correlates with patient outcome after Inotuzumab Ozogamicin treatment

“…Currently, treatment options directed against CD22 (INO) and CD19 (Blinatumomab, CAR) are available for R/R B-ALL, but no head-tohead prospective trial comparisons have been performed. [26][27][28] Physicians' treatment choice relies on disease and patient characteristics, comorbidities, therapeutic program, previous therapies and, necessarily, target antigen expression. 29,30 Real-life findings that support data from clinical trials and aim to identify better disease indicators and prognostic factors remain a priority for physicians.…”