Low Dose Steroids Can Improve High Grade Febrile. Episodes Associated with Blinatumomab Therapy and. Limit Treatment Interruptions without Affecting Anti-.
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
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Low Dose Steroids Can Improve High Grade Febrile Episodes Associated with Blinatumomab Therapy and Limit Treatment Interruptions without Affecting AntiLeukemic Effects Shahram Mori 1, Wesam Ahmed 2, Rushang D. Patel 2, Rebecca Jean Nelson 3. 1 Bone Marrow and Cellular Therapy, Florida Hospital Cancer Institute, Orlando, FL; 2 Florida Hospital Cancer Institute, Orlando, FL; 3 Florida hospital, orlando, FL Low Dose steroids can improve high grade febrile episodes associated with blinatumomab therapy and limit treatment interruptions without affecting anti-leukemic effects Background: Relapsed/refractory precursor B cell acute lymphoblastic leukemia (B cell ALL) carries a poor prognosis in adults. Allogeneic stem cell transplantation is the only potentially curative treatment for majority of such patients. Blinatumomab is a recently approved bi-specific CD19directed CD3 T-cell engager (BiTE) antibody in B-cell ALL patients who have failed induction chemotherapy1. Its administration however is commonly complicated by grade III-IV toxicities including high-grade fevers and Cytokine Release Syndrome (CRS) defined as elevations in ferritin levels, pro-inflammatory cytokines such as IL-6 and clinical features of fevers, chills and vascular leak2. These complications can result in in premature treatment interruptions, failures as well as treatment-related mortality. At this time, concomitant use of low doses of steroids with Blinatumomab can alleviate these symptoms without negatively impacting the efficacy of treatment. Methods: Three patients with refractory/relapsed Ph(-) B-cell ALL who had all failed HyperCVAD chemotherapy, received blinatumomab (9 mg/day for the first 7 days and 28 mg/day thereafter) by continuous intravenous infusion over 4 weeks as outlined by the manufacturer. Ferritin, fibrinogen and interleukin-6 levels were measured to monitor for the development of significant cytokine release syndrome. Solumedrol at 5 or 10mg IV BID was given to patients 1 and 2 upon the development of high-grade temperature (>102). The third patient was started on solumedrol at 5mg IV BID at the time of initiation of Blinatumomab. Clinical Course/ Findings: Patient 1 is a 52 yo female with 67% blasts in the bone marrow (BM). Patient 2 is a 51 yo male began therapy with persistent leukemia (7-10% blasts in the BM). Patient 3 is a 48 yo male with 90% blasts cells in the BM. All began blinatumomab per manufacturer’s instructions. Patients one and two were not prophylactically started on low dose steroids and required 2 and one dose interruptions of BiTE antibody respectively. All patients were off solumedrol before day 5 of treatment. No treatment interruptions were required in the third patient. All patients experienced elevated ferritin and fibrinogen levels with high grade fevers. Elevated IL-6 levels in patient 3 did not correlate with CRS (Figure 1A and 1B). All patients achieved a CR (morphological and by flow cytometry) at the end therapy. Patients one and two are currently 6 months post-transplant and remain in CR. Patient three is awaiting allogeneic stem cell transplantation. Conclusion: Low dose steroids can attenuate high grade fevers with Blinatumomab, limit treatment interruptions and potentially protect the development of CRS without compromising anti-leukemic effects.
Allogeneic Hematopoietic Stem Cell Transplant Outcomes in Patients with Acute Erythroleukemia Hassan B. Alkhateeb 1, Moussab Damlaj 1, Mehrdad Hefazi 2, Ajoy Dias 1, Shahrukh K. Hashmi 1, William J. Hogan 1, Mark R. Litzow 1, Mrinal S. Patnaik 3. 1 Division of Hematology, Mayo Clinic, Rochester, MN; 2 Department of Internal Medicine, Mayo Clinic, Rochester, MN; 3 Division of Hematology, Mayo Clinic Rochester, Rochester, MN Background: Acute erythroleukemia (AEL) is an aggressive neoplasm with a median survival of < 12 months. Outcomes are better with allogeneic stem cell transplantation (HCT) however; most studies were based on the FAB ( 30% myeloblasts) classification. There have been no studies to date, reassessing clinical outcomes, using the 2008 WHO definition (Swederlow et al. 2008).We carried out this study to specifically answer this question. Methods: After IRB approval, the acute leukemia database (923 patients) at the Mayo Clinic was queried for AEL. 43(4.6%) pts met the 2008 WHO criteria. Bone marrow biopsy slides, cytogenetics and clinical characteristics were retrospectively reviewed. Cytogenetic risk stratification was based on the NCCN AML guidelines. Standard statistical analyses were carried out. Results: The median age at diagnosis was 65 years (27-90) and 34(79%) were male. 30(69%) had M6a and 13 (30%) had M6b. 27(62%) had de novo AML while 16 (37%) had secondary AML (9 MDS and 7 therapy related). The median time to leukemic transformation for pts with MDS was 8 months (2-83). Median follow up in our cohort was 7.2 months (2157) at which time 13(30%) deaths were documented. A. Patient characteristics: At diagnosis median laboratory values included; Hemoglobin 8.5 g/dL (4.6-11), WBC 2x1010 (0.7-11.1), ANC 0.47x1010 (0.01-4.07), Platelet 33x 1010 (7-177), peripheral blast % 2 (0-35), and bone marrow blast % 11 (0-84). Cytogenetic information was available in 38 pts; of which 6(16%) were diploid, 21(55%) were complex/monosomal and 1(3%) was complex/non monosomal. Intermediate risk cytogenetic was observed in 15 pts (39%), and poor risk cytogenetics were identified in 23(61%). Patients with AMLM6a were more likely to have neutropenia and a higher bone marrow blast %, in comparison to those with AML-M6b (p 0.047 & 0.0027 respectively). None of the patients had extramedullary disease or CNS involvement. B. Stem Cell Transplant Characteristics: Of the 43 pts, 7 received best supportive care, and of the pts who received chemotherapy, 13 achieved CR1, and 4 achieved CR2. Of these 10(77%) and 2(50%) underwent HCT (autologous-1, allogeneic-11; 3-MRD and 8-MUD). Conditioning regimens included; Flu/Mel-6, Flu/Bu-1 (RIC), and Cy TBI-5 (MA). C. Stem Cell Transplant Outcome: Median survival from transplant was 66 months (2.6-NR) during which time 6 deaths occurred (2 related to relapse; both in CR2 at time of HCT). Incidence of acute GVHD (all grades) was 50% and chronic GVHD 33%. HCT improved overall survival with a median of 89 months (9.4-NR), compared to 5 months (2.110.9) for those who did not undergo HCT (p 0.0031) (Figure1). Conclusion: Acute Erythroid Leukemia is rare and had a prevalence of w5% in our AML cohort. Due to age and the refractory nature of the disease
