Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study

Abstract

Background Inotuzumab ozogamicin (InO) is an antibody‐drug conjugate used for adults with relapsed/refractory B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO‐VATE) previously reported improved outcomes with InO versus standard‐of‐care (SoC) chemotherapy. This article reports the final INO‐VATE results (≥2 years of follow‐up) and additional analyses of patient characteristics associated with improved outcomes. Methods Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open‐label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm). Results The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1‐sided P < .0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2‐year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval [CI], 0.57‐0.99; 1‐sided P = .0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow‐up hematopoietic stem cell transplantation (HSCT; all 2‐sided P values < .05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow‐up induction therapy (39.6% [95% CI, 32.1%‐47.6%] vs 10.5% [6.2%‐16.3%]; 1‐sided P < .0001). The most frequent all‐grade and grade 3 or higher adverse events in both arms were hematologic. Veno‐occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 [14.0%] vs 3 of 143 [2.1%]). Conclusions In patients with relapsed/refractory BCP ALL in INO‐VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made.

Results from an international phase 2 study of the anti‐CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B‐lineage acute lymphoblastic leukemia

“…The etiology for ocular dysfunction remains unclear but may potentially be related to underlying capillary leak; ocular dysfunction was also seen in the corresponding phase 1 study and is included in the FDA package insert for this drug. Notably, moxetumomab pasudotox has not been associated with VOD/SOS, differentiating it from an established toxicity of IO . Ultimately, the study was terminated upon the interim analysis because the CRc rate did not reach the stage 1 target.…”

Treating Leukemia in the Time of COVID-19

“…Salvage Therapies. Patient who are COVID-19-negative with relapsed or refractory ALL should receive salvage therapy with lower intensity regimens such as mini-HCVD and inotuzumab followed by blinatumomab [13,[29][30][31][32]. Patients in second complete remission can be considered for allogeneic SCT as the chances of relapse are high.…”

Cost Effectiveness of Blinatumomab Versus Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia in the United States

“…The CR rate was higher among patients receiving inotuzumab than SOC (34% vs 16% p = 0.0001) [15]. In long-term follow-up, median OS was 7.7 versus 6.2 months with inotuzumab versus SOC (HR 0.75; 97.5% CI 0.568-0.993; p = 0.0105) [16]. Venoocclusive disease (VOD) was observed in 11.6% of patients receiving inotuzumab [16].…”

“…In long-term follow-up, median OS was 7.7 versus 6.2 months with inotuzumab versus SOC (HR 0.75; 97.5% CI 0.568-0.993; p = 0.0105) [16]. Venoocclusive disease (VOD) was observed in 11.6% of patients receiving inotuzumab [16]. Hematopoietic stem cell transplant was received by 43% of patients receiving inotuzumab and 11% of patients receiving SOC [16].…”