Idoroenyi Amanam

CD19‐directed therapy remains the mainstay treatment for relapsed/refractory B‐cell acute lymphoblastic leukemia (ALL). However, treatment patterns and outcomes following CD19‐negative (CD19‐) relapse remain poorly defined. We retrospectively analyzed 65 adult patients with ALL who developed CD19‐relapse after CD19‐directed therapy. TP53 mutations and BCR::ABL1 ‐like ALL were each identified in 27.7% ( n = 18) of patients. Forty‐six patients (70.8%) received one CD19‐targeted therapy, whereas 19 patients (29.2%) received ≥ 2 prior to CD19‐relapse. Overall, 60 patients (92.3%) received blinatumomab, and 23 (35.4%) received CAR T‐cell therapy. The median time from the initiation of the most recent CD19‐targeted therapy to CD19‐relapse was 155 days (range, 13–1946). The median follow‐up of the entire cohort was 32.7 months (IQR, 15.1–90.3). The median event‐free and overall survival (EFS and OS) was 3.1 months (95% CI, 2.5–4.5) and 9.9 months (95% CI, 6.8–24.7), respectively. In multivariate analysis, receipt of ≥ 2 CD19‐directed therapies was associated with both inferior EFS and OS, HR 2.17 (95% CI, 1.10–4.29; p = 0.03) and HR 3.05 (95% CI, 1.40–6.62; p = 0.005). The complete remission rate following first salvage therapy was 47.5% and 72.1% any time following CD19‐relapse. Sixteen (34.8%) of 46 patients evaluated had subsequent CD19 re‐expression, 5 of whom subsequently received CD19‐directed therapy, and all 5 patients responded. Patients with ALL who develop CD19‐relapse after CD19‐directed therapy have poor outcomes and limited therapeutic options. However, since this study lacked a comparator cohort of patients with CD19‐positive relapse, the independent prognostic impact of CD19 negativity could not be determined.

Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature. Methods: Sixty patients with steroid-refractory aGVHD were analyzed. The primary objective was to determine the overall response rate (ORR) for CCBT. Secondary outcomes included non-relapse mortality (NRM) and overall survival (OS). Results: ORR for CCBT at day 7, 14, and 28 were 28.3% (17/60; CR 5.0%/PR 23%), 38.3% (23/60; CR 11.3%/PR 27%), and 38.3% (23/60; CR 23.3%/PR 15%), respectively. Patients who received ruxolitinib prior to CCBT had lower ORR (25% CR = 15%/PR = 10%) compared to those who did not (47.5% CR = 27.5%/PR = 20%). In patients with and without ruxolitinib initiated prior to CCBT, NRM at 6 months was 60% (95% CI, 34.5–78) and 47.5% (95% CI, 31–62), while OS at 12 months was 30% (95% CI, 12–50) vs. 40% (95% CI, 25–55), respectively. Conclusions: CCBT has shown potential efficacy in steroid-refractory GI aGvHD, and given the observed ORR when used as second-line therapy, CCBT could serve as an acceptable alternative for patients who are ruxolitinib-intolerant. Ruxolitinib-refractory GI GvHD remains an area of unmet need and CCBT can provide salvage therapy for some patients.

The accurate diagnosis and classification of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) are challenging due to the overlapping pathological and molecular features of myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). We investigated the genomic landscape in different MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 97), atypical chronic myeloid leukemia (aCML; n = 8), MDS/MPN-unclassified (MDS/MPN-U; n = 44), and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 12). Our study indicated that MDS/MPN is characterized by mutations commonly identified in myeloid neoplasms, with TET2 (52%) being the most frequently mutated gene, followed by ASXL1 (38.7%), SRSF2 (34.7%), and JAK2 (19.7%), among others. However, the distribution of recurrent mutations differs across the MDS/MPN subtypes. We confirmed that specific gene combinations correlate with specific MDS/MPN subtypes (e.g., TET2/SRSF2 in CMML, ASXL1/SETBP1 in aCML, and SF3B1/JAK2 in MDS/MPN-RS-T), with MDS/MPN-U being the most heterogeneous. Furthermore, we found that older age (≥65 years) and mutations in RUNX1 and TP53 were associated with poorer clinical outcomes in CMML (p < 0.05) by multivariate analysis. In MDS/MPN-U, CBL mutations (p < 0.05) were the sole negative prognostic factors identified in our study by multivariate analysis (p < 0.05). Overall, our study provides genetic insights into various MDS/MPN subtypes, which may aid in diagnosis and clinical decision-making for patients with MDS/MPN.

Introduction: In November 2020, the FDA issued an emergency use authorization (EUA) for monoclonal antibody (mAb) therapy in patients with mild‐to‐moderate COVID‐19 at high risk for disease progression.Methods: We retrospectively reviewed 38 adult hematology patients who received mAbs from 11/2020 to 2/2021.Results: Thirty (79%) patients received bamlanivimab and 8 (21%) casirivimab‐imdevimab. Four (11%) patients were hospitalized due to COVID‐19, two (5%) progressed to severe disease and one patient (3%) died within 30 days from COVID‐19 disease. Most patients (n = 34, 89%) ultimately tested negative for SARS‐CoV‐2, with 34% (n = 13) clearing the virus within 14 days after mAb infusion. The median time to clearance of viral shedding was 25.5 days (range: 7–138). After mAb infusion, most patients with hematological malignancies (HM) (n = 10/15; 67%) resumed therapy for underlying disease with a median delay of 21.5 days (range: 12–42). We observed a significant difference in hospitalization among patients who received a HCT versus non‐HCT (0% n = 0/26 and 36% n = 4/11, respectively; p < 0.01).Conclusions: This study demonstrates that SARS‐CoV‐2 specific mAb was safe and may reduce hospitalization compared to what is reported in malignant hematology patients at high risk for disease progression. Our HCT cohort patients had less hospitalization rate compared with HM cohort patients.

Philadelphia (Ph)‐like acute lymphoblastic leukemia (ALL) is associated with a poor response to standard chemotherapy. However, outcomes with novel antibody and cellular therapies in relapsed/refractory (r/r) Ph‐like ALL are largely unknown. We conducted a single‐center retrospective analysis of adult patients (n = 96) with r/r B‐ALL and fusions associated with Ph‐like who received novel salvage therapies. Patients were treated with 149 individual novel regimens (blinatumomab = 83, inotuzumab ozogamicin [InO] = 36, and CD19CAR T cells = 30). The median age at first novel salvage therapy was 36 years (range; 18–71). Ph‐like fusions were IGH::CRLF2 (n = 48), P2RY8::CRLF2 (n = 26), JAK2 (n = 9), ABL‐class (n = 8), EPOR::IGH (n = 4) and ETV6::NTRK2 (n = 1). CD19CAR T cells were administered later in the course of therapy compared to blinatumomab and InO (p < .001) and more frequently in recipients who relapsed after allogeneic hematopoietic cell transplantation (alloHCT) (p = .002). Blinatumomab was administered at an older age compared to InO and CAR T‐cells (p = .004). The complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates were 63%, 72%, and 90% following blinatumomab, InO and CD19CAR, respectively, among which 50%, 50%, and 44% of responders underwent consolidation with alloHCT, respectively. In multivariable analysis, the type of novel therapy (p = .044) and pretreatment marrow blasts (p = .006) predicted the CR/CRi rate, while the Ph‐like fusion subtype (p = .016), pretreatment marrow blasts (p = .022) and post‐response consolidation with alloHCT (p < .001) influenced event‐free survival. In conclusion, novel therapies are effective in inducing high remission rates in patients with r/r Ph‐like ALL and successfully transitioning the responders to alloHCT.

Rearrangements of lysine [K] methyltransferase 2 A (KMT2A) gene, previously known as the MLL gene, occur in 3 to 7% of adult patients with de novo AML and are enriched in therapy-related disease, p...