Prognostic implications of cytogenetics in adults with acute lymphoblastic leukemia treated with inotuzumab ozogamicin

Abstract

Karyotype is frequently used to predict response and outcome in leukemia. This post hoc exploratory analysis evaluated the relationship between baseline cytogenetics and outcome in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) treated with inotuzumab ozogamicin (InO), a humanized CD22 antibody conjugated to calicheamicin, in the phase 3, open‐label, randomized INO‐VATE trial. Data as of March 8, 2016, are presented in this analysis. Of the 326 patients randomized, 284 had screening karyotyping data (144 in the InO arm and 140 in the standard care [SC] arm). With InO, complete remission or complete remission with incomplete hematologic recovery (CR/CRi), minimal residual disease negativity rates, and overall survival (OS) were not significantly different between cytogenetic subgroups. CR/CRi rates favored InO over SC in the diploid with ≥20 metaphases, complex, and “other” cytogenetic subgroups. The OS hazard ratio favored InO over SC in the diploid with ≥20 metaphases, complex, and other cytogenetic subgroups. Generally, InO is effective and provides substantial clinical benefit in patients with R/R ALL who have specific baseline karyotypes.

Long‐term follow‐up of salvage therapy using a combination of inotuzumab ozogamicin and mini–hyper‐CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome–negative acute lymphoblastic leukemia

“…Our analysis identified independent baseline characteristics predictive of poor outcome: cytogenetic abnormalities ( KMT2A rearrangements and low hypodiploidy/near triploidy) and CD22 expression level of <70%. This is in line with the findings of previous reports for standard chemotherapy and inotuzumab 23‐25 . Expansion of this analysis to include mutated TP53 is warranted, particularly in patients without low hypodiploidy.…”

“…This is in line with the findings of previous reports for standard chemotherapy and inotuzumab. [23][24][25] Expansion of this analysis to include mutated TP53 is warranted, particularly in patients without low hypodiploidy. Baseline cytogenetic profiles play a key role in determining prognosis.…”

Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children's Oncology Group Protocol AALL1621

“…However, some patients with low ABC did respond; no clear threshold was identified for dim expression that would preclude InO response. Patients with KMT2A-R, who commonly have lower ABC and/or partial CD22 expression, 21,22 had poor responses; zero of six patients achieved MRD-negative CR or CRi, consistent with adult outcomes. 23 One patient with KMT2A-R demonstrated myeloid lineage switch following subsequent CD19 CAR T-cell therapy; it is unknown whether InO exposure contributed as lineage switch has been reported with CD19-targeted therapy.…”

Sequencing antigen‐targeting antibodies and cellular therapies in adults with relapsed/refractory B‐cell acute lymphoblastic leukemia

“…All the novel therapies described above show promising activity across various high‐risk genetic subgroups 14,76–79 . Interestingly, data from China showed a lower response rate to CD19 CAR T‐cell therapy in patients with TP53 mutations 64,80 .…”

“…All the novel therapies described above show promising activity across various high-risk genetic subgroups. 14,[76][77][78][79] Interestingly, data from China showed a lower response rate to CD19 CAR T-cell therapy in patients with TP53 mutations. 64,80 Another genetic subset of interest is KMT2A-rearranged (KMT2Ar) ALL because of its propensity to undergo a lineage switch to a myeloid phenotype under the pressure of CD19-targeted treatments.…”