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Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell product targeting CD19 is approved for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the impact of pretreatment variables, such as CD19 expression level, on leukemic blasts, the presence of CD19(–) subpopulations, and especially prior CD19-targeted therapy, on the response to CAR T-cell therapy has not been determined. We analyzed 166 patients treated with CAR T-cell therapy at our institution. Eleven patients did not achieve a minimal residual disease (MRD)(–) deep remission, whereas 67 patients had a recurrence after achieving a MRD(–) deep remission: 28 patients with CD19(+) leukemia and 39 patients with CD19(–) leukemia. Return of CD19(+) leukemia was associated with loss of CAR T-cell function, whereas CD19(–) leukemia was associated with continued CAR T-cell function. There were no significant differences in efficacy of CAR T cells in CD19-dim B-ALL, compared with CD19-normal or -bright B-ALL. Consistent with this, CAR T cells recognized and lysed cells with very low levels of CD19 expression in vitro. The presence of dim CD19 or rare CD19(–) events by flow cytometry did not predict nonresponse or recurrence after CAR T-cell therapy. However, prior therapy with the CD19-directed, bispecific T-cell engager blinatumomab was associated with a significantly higher rate of failure to achieve MRD(–) remission or subsequent loss of remission with antigen escape. Finally, immunophenotypic heterogeneity and lineage plasticity were independent of underlying clonotype and cytogenetic abnormalities.

Background: Hepatitis B infection may be associated with an increased risk of non hodgkins lymphoma, especially diffuse large B cell lymphoma. Whether an intact immune system is required hepatitis B mediated lymphomagenesis and if factors such as other viral co infections and paraproteins may further compound this risk remains unclear. We retrospectively studied our large database of HBsAg positive patients for diagnoses of hematological malignancies or premalignant disorders (HM) and the risk factors for their development. Methods: Patients over the age of 18 with at least one positive HBsAg test between Jan 1st 2001 and Dec 31st 2011 were identified using the medical center database, clinical looking glass. Data were collected regarding demographics, HIV and hepatitis C status. Serum protein electrophoresis tests done after the HBsAg test were reviewed. Results of all biopsies performed for each patient, ICD9 and cancer registry diagnoses were reviewed for biopsy confirmed diagnoses of a HM. Liver biopsy results were reviewed for evidence of chronic hepatitis changes. Results: 3177 of 216,522 patients (1.5%) tested were HBsAg positive. Mean age of the HBsAg positive group was 43 years, 56% were male. 44% were black, 8% white and 7.4% were Asian. 33.6% of these patients had two positive HBsAg tests 6 months apart. 10.3% of patients underwent a liver biopsy and 9.4% of patients had biopsy changes consistent with chronic hepatitis. Of the 3177 patients, 4.9% (155 patients) had a biopsy of any lymphatic tissue or bone marrow performed. 2.2 % (71 patients) had a hematological malignancy or premalignant disorder diagnosed. 0.4% (12 patients) had an insufficient specimen for diagnosis and were excluded from further analysis. Of the 71 patients with a HM, 30 (42.3%) had a high grade B or T cell lymphoma; 12 (16.9%) had myeloma or smoldering myeloma; 11 (15.5%) had a low grade lymphoma; 6 (8.4%) had myelodysplasia, myeloproliferative disorder or acute leukemia and 11 (15.5%) had a premalignant disorder including multicentric castleman, MGUS or NK cell lymphocytosis. 47% of high grade lymphomas occurred in an extranodal location. Within the HBsAg positive population, HM positive patients (n=71) compared to HM negative controls (n=3094) were significantly older (52.5 vs 43 yrs, p

Background An increasing incidence of hematological malignancies (HM) has been noted in HIV+ patients, however the risk factors remain unclear. We retrospectively explored our large database of HIV+ patients to assess the incidence and distribution of different HM and premalignant hematological disorders (PMD) in HIV+ patients and the HIV and non HIV related risk factors for development. Methods Patients over the age of 18 with a positive HIV test (western blot or detectable viral load) between Jan 1st 2001 and Dec 31st 2011 were identified using the medical center database Clinical Looking Glass. Data were collected regarding demographics, Hepatitis B, C status, paraproteinemia and HIV characteristics. Results of all biopsies performed for each patient, ICD9 and cancer registry diagnoses were reviewed for a diagnosis of hematological malignancy (HM). Data collection was censored as of April 1st 2013. Results 10,293 patients with a positive HIV test were identified with a median duration of follow up of 60 months (0-146 months) from the test date. 747 of these patients underwent a total of 948 biopsies for diagnosis of hematological disorders. 46 patients were excluded for an insufficient biopsy specimen. 255 of 10,293 patients (2.5%) were diagnosed with a HM or PMD. 241 patients had biopsy confirmation and 14 patients had ICD9 code/cancer registry data which were confirmed by chart review. Ten patients were diagnosed with HM when their HIV status was unknown and were excluded. 2 of the remaining 245 HM positive patients had two HM each, myeloma followed by extranodal NK/ T cell lymphoma and Castleman followed by DLBCL. Mean age at diagnosis of the first HM/PHD was 46 years (SD:9.9). HM positive cases (n=245) in comparison to HM negative (n=9992) controls were more likely to be male (69% vs 57.6%, p The distribution of HM is noted in Table 1. High grade lymphomas accounted for 80.6% of HM, with DLBCL being the most frequent category. Of all HM, 43.5% occurred as non-nodal primaries The closest CD4 count within 6 months prior to HM diagnosis was obtained and median CD4 count compared. High grade lymphomas had a significantly lower median CD4 count close to HM diagnosis compare to low grade lymphomas and plasma cell dyscrasias. (150 vs 314 vs 281, p: 0.012) Conclusion Our study suggests that in HIV related HM, male gender and discrete paraproteins are likely to be significant risk factors but oligoclonal or multiple paraproteins are not. No additional risk appeared to be conferred by concurrent viral illnesses. The relationship of CD4 count to HM development suggests the role of immune mechanisms in pathogenesis. Disclosures: No relevant conflicts of interest to declare.

Abstract 1827 BACKGROUND: Prior studies suggest that HIV+ patients have a higher prevalence of paraproteinemia. Paraproteinemia is a known risk factor for development of hematological malignancy (HM) in non HIV patients. However the pathogenesis of paraproteinemia and the additional risk conferred by it to development of HM in HIV remains unclear. We describe our findings from a large database of HIV+ patients in Montefiore Medical Center with and without paraprotein for differences in HIV status, comorbidities and incidence of HM. METHODS: Our de-identified patient database, Clinical Looking Glass, was used to identify all documented HIV+ patients who underwent at least one serum protein electrophoresis test (SPEP) after the HIV test between January 1st 2001 and December 31st 2011. Patients were classified into SPEP+ and SPEP-, and SPEP+ patients further stratified into distinct (D-SPEP) or faint/multiple/oligoclonal (F-SPEP) cases by visual assessment of gel electrophoresis. Laboratory data was reviewed for comorbidities and HIV status. Results of all biopsies undergone by each patient were reviewed to identify HM diagnoses. RESULTS: A total of 17,961 HIV+ patients were identified of which 2,095 patients had at least one SPEP test. Of those tested, 21.2% were SPEP+ (D-SPEP: 4%; F- SPEP:17.2%). 3.3% had a missing result. IgG was the commonest subtype on immunofixation (85.4%). All 3 groups (SPEP-, D-SPEP and F-SPEP) had a similar median duration of HIV before testing for SPEP. Mean CD4+ value measured around the time of the SPEP test (3 months before or after) was significantly higher in the F-SPEP group compare to both other groups. Patients in the D-SPEP and F-SPEP groups were more likely to be seropositive for Hepatitis C and Rheumatoid Factor (RF) than those who were SPEP-. A significantly higher proportion of patients were biopsied in the D-SPEP and F-SPEP groups than the SPEP-. Overall the incidence of HM in D-SPEP was significantly higher but when adjusted for patients who were biopsied, the higher incidence in D-SPEP did not reach statistical significance. 50–60% of HM were diagnosed within 6 months of the index SPEP; the D-SPEP group had the shortest time to diagnosis of HM after SPEP. The pattern of HM was different among the three groups with the D-SPEP patients mostly developing plasma cell dyscrasias, while the F-SPEP and SPEP- groups had a higher proportion of high grade B and T cell neoplasms. (Table 1). CONCLUSIONS: To our knowledge this is the largest published sample of HIV+ patients tested for paraproteinemia. The higher prevalence of Hepatitis C in SPEP+ patients suggests its role in pathogenesis of paraproteinemia. The higher incidence of HM, especially plasma cell dyscrasias diagnosed close to the index SPEP in the D-SPEP group suggests that D-SPEP may reflect malignant clonal proliferation. In contrast, the F-SPEP group had a similar HM incidence to SPEP- and a higher CD4+ count than the other groups. These suggest that faint/oligoclonal paraproteins may require T cell mediated B cell activation to develop and maybe directed against viral antigens rather than reflect premalignant or malignant proliferation. Understanding antigen specificity of paraproteins may shed light on the risk of HM in HIV+ SPEP+ patients. Disclosures: No relevant conflicts of interest to declare.