JAK2 fusion

In contrast to MF/SS, PCAETCL and PCGDTCL remain diseases with few prospective studies to guide treatment. However, recent genomic insights on these diseases, such as the presence of JAK2 fusions in PCAETCL and cell of origin findings in PCGDTCL, have created options for new biomarker-driven strategies.

HE requires a wide diagnostic evaluation with a multidisciplinary approach and the development of working groups in order to avoid these inconclusive diagnosis (12% in our series) and the missing diagnostic tests. Our study suggests the association between elevated LDH, cobalamins and tryptase and clonal cause of HE, as well as a higher rate of fibrosis, medullary dysplasia and altered karyotypes in these patients, indicating the need to include these evaluations in the diagnostic process. The group of PDGFRα patients had good prognosis with imatinib, but one patient presented clonal evolution and blastic transformation, showing the clinical challenge of these entities.

The addition of 14 days of VEN at 400 mg daily dose to a pediatric-inspired regimen during IND and CONS was safe in adults with newly diagnosed B-ALL and did not delay counts recovery. The addition of VEN led to a promising higher than expected MRD- CR rate in high-risk B-ALL, including for pts with Ph-like subtype. The study is actively enrolling on the expansion cohort, and BH3 profiling on pre-treatment and post relapse samples will be performed to determine BCL-2 dependency and correlates to early MRD- response.

In 8/15 patients ponatinib was used as single agent or in association with steroids or intrathecal chemotherapy only, in 4 it was administered in combination with chemotherapy and in 3 with blinatumomab; 7 patients started ponatinib after having failed an allogeneic transplant (6 hematologic relapses and 1 molecular relapse). In a pre-transplant setting, ponatinib was effective as a bridge to cellular therapies in 7 out of 8 patients as intention-to-treat (ITT), thus suggesting that this strategy may represent an effective bridge to further therapies. To our knowledge, this is the largest cohort of adult Ph-like ALL cases treated with ponatinib so far reported.

The case suggests a mucocutaneous variant of primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T-cell lymphoma, highlighting the diagnostic challenges inherent in diagnostic dermatopathology. Poster type: Poster Defense

The comparison between patients with PDGFRA/PDGFRB vs. FGFR1, JAK2, and ETV6::ABL1 fusion genes revealed a similar occurrence of primary BP (17/104, 16% vs. 8/31 26%, p = 0.32), a lower frequency (5/87, 6% vs. 8/23, 35%, p = 0.003) of and a later progression (median 87 vs. 19 months, p = 0.053) into secondary BP, and a better overall survival from diagnosis of BP (17.1 vs. 1.7 years, p < 0.0008). We conclude that hypereosinophilia with or without monocytosis and various phenotypes of BP occur at variable frequencies in MLN-TK.

However, long-term efficacy remains to be determined and it is under evaluation in clinical trials.1,22,23 Preclinical and more recent clinical studies have shown variable activity of JAK inhibitors in JAK-STAT activating ALL17,24 and the need to simultaneously inhibit multiple pathways, including phosphoinositide 3-kinase (PI3K)/mTOR or mitogen-activated protein kinase (MEK)/ receptor tyrosine kinases (e.g. FLT3) to block the growth of leukemic blasts.25–27 Promising alternative approaches to TKIs are represented by antibody-based (e.g. blinatumomab or inozutumab) and cellular (CAR T-cell therapy) immunotherapy which have shown discernable efficacy in BCR::ABL1-like ALL among other subtypes.28–30 Moreover, the efficacy of proteolysis-targeting chimeras (PROTACs) directed against JAK231 or GSPT1/2 degraders32 has been recently reported in preclinical models of CRLF2-rearranged and other JAK-activated BCR::ABL1-like ALL. Conclusions BCR::ABL1-like ALL is driven by numerous targetable kinase fusions whose diagnosis requires the use of comprehensive assays. The incorporation of TKIs and/or different immunotherapies is reversing the historically poor outcome of this ALL subtype.