Anti-IDH2 (mutation R172S) Monoclonal Antibody, clone XH072

Acute myeloid leukemia (AML) is a heterogeneous disease and the results of previous treatment with cytotoxic drugs have not been satisfactory. This situation has prompted investigations into novel approaches. The breakthrough in therapy brought by all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) and tyrosine kinase inhibitors in neoplasms with the Philadelphia chromosome has encouraged the search for other effective targeted therapies. Among the tested substances are higher molecular mass drugs such as antibodies and various small molecules: kinase inhibitors, cell pathway inhibitors and epigenetic modulators. So far, the U.S. Food and Drug Administration (FDA) has approved the antibody-drug conjugate gemtuzumab ozogamycin (GO), the tyrosine kinase inhibitor midostaurin and the IDH2 inhibitor enasidenib. These studies have led to a better understanding of the mechanisms of leukemogenesis and may soon allow for differentiating treatments depending on baseline mutational complements. Some innovative drugs described in this article have strong therapeutic potential, but there is still a long way to go before actual success in targeted treatment.

Angioimmunoblastic T-cell lymphoma (AITL) carries genetic mutations of TET2, RHOA, and IDH2, but the prognostic impact of these mutations is not widely investigated. Although one study shows no difference in overall survival between patients with or without RHOA G17V mutation, a poor performance status is associated with RHOA G17V-mutated AITL, which is an independent adverse factor. We retrospectively investigated the prognostic impact of RHOA G17V mutation in AITL patients. A total of 31 cases were enrolled (male-to-female, 2.1; mean age: 62.8 years). RHOA G17V mutation was analyzed by deep sequencing. We found that in contrast to RHOA-wild type, patients with RHOA G17V-mutated AITL more frequently had B symptoms (p = .035), stronger PD1 expression (p = .045), >= 3 TFH markers (p = .011), higher blood vessel density (p<.001), and poorer progression-free survival (p = .046). These results support a role for RHOA genetic testing in AITL patients as ROHA G17V mutation carries a worse prognosis, probably associated with B symptoms and stage IV disease.