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Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for approximately 25% of all newly diagnosed patients (Swerdlow et. al. IARC, 2017). It is estimated that 40% of patients are refractory to, or relapse after treatment with chemo-immunotherapy (R-CHOP). Salvage therapy with autologous stem-cell transplantation (ASCT) can cure around 40% of those patients, nevertheless, the prognosis is poor for most patients with R/R DLBCL who are relapsed after, or ineligible for ASCT, and in those with suboptimal response to salvage chemotherapy. Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate delivering monomethyl auristatin E (MMAE), a microtubule inhibitor. It was granted accelerated approval by the US FDA on June 2019 for treatment of R/R DLBCL after at least two prior therapies, in combination with bendamustine and rituximab. We herein report our experience on the use of polatuzumab in patients with R/R DLBCL. Methods: Retrospective-single center review on the use of polatuzumab vedotin as part of a compassionate program in patients with R/R DLBCL between June 2018 and July 2021. Inclusion criteria for the study were: age ≥ 18 years, R/R DLBCL [both de-novo and transformed lymphoma], 2 or more prior lines of therapy, and treatment with polatuzumab-based therapy for at least 1 cycle. Patients with CNS involvement were excluded. The compassionate use access program provided polatuzumab at a dose of 1.8 mg/kg, administered with or without bendamustine (up to two doses of 90 mg/m2,) and rituximab (375 mg/m2). Treatment was given every 21 days for up to 6 cycles. Results: we identified 3 patients with R/R DLBCL who were treated with polatuzumab-based therapy. The median number of prior therapies was 2 (2 - 5). The median IPI and CNS-IPI score were 2, (1 - 4) and 2, (2 - 5), respectively (Baseline characteristics are summarized in Table). The median number of Pola-BR cycles received was 3 (2 - 6). One patient completed 6 cycles of polatuzumab with bendamustine and rituximab and achieved partial response. The other two patients were taken of treatment at the time of progression on cycles number 1 and 3. Treatment options were limited after polatuzumab-based therapy. The patient who achieved partial response after 6 cycles of Pola-BR maintained that response for 11 months without additional treatment and died due to COVID-19 associated pneumonia. One patient been screened for Glofitamab compassionate use program, and one patient elected to receive no further therapy. Conclusions: Polatuzumab-based treatment in R/R DLBCL is a promising treatment in an otherwise difficult to treat patient population. The compassionate use program provides access in developing countries to an otherwise prohibitively expensive emerging therapeutic armamentarium in R/R DLBCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Hodgkin lymphoma (HL) is an uncommon B-cell malignant neoplasm, with high curable rate for patients with localized disease or advanced.However, up to 30% of patients with HL are either refractory or relapsed after primary treatment. Salvage chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the standard of care for eligible patients in relapsed setting. Brentuximab vedotin and Bendamustine (BvB) combination have been recommended by National Cancer Center Network (NCCN) as one of the salvage regimens for patients with relapsed or refractory HL prior to transplant or who relapsed after hematopoietic stem cell transplant (HSCT). Evidence from retrospective and prospective studies in regards of BvB have shown remarkable progression free survival (PFS) with 2-years PFS ranging from 62.2% up to 93.7%, and overall survival (OS) ranging from 88.1% up to 95%, and complete remission (CR) rates ranging from 43% to 90%. The objective of this study is to assess patient response to BvB in the treatment of relapsed/refractory HL especially for patients beyond first salvage therapy unlike many other studies. Methods: A retrospective study was conducted in patients with relapsed/refractory Hodgkin lymphoma treated with BvB chemotherapy at single tertiary hospital from January 2016 until July of 2021. Data collection was done including patient demographics data, comorbidities, disease stage, lines of chemotherapy regimens taken, and PET scan response with Deauville score. Brentuximab was given as 1.8mg/kg on day 1, and bendamustine was given as 90mg/m 2 on day 1 and day 2. Cycle was repeated every three weeks. Result: A total of 16 patients with relapsed/refractory HL whom treated with BvB chemotherapy were analyzed. Median age is 29 years (22-70 years), 5 patients were female, and median number of lines of therapy prior to starting BvB is 2 (0-5). The median number of cycles of BvB was 5.5 (3-8 cycles). 2 out of 16 patients had a prior autologous HSCT (12.5%). 15 patients were assessed for response and one patient died before disease assessment. The overall response rate was 80% with 50% of patients achieving complete metabolic response on PET scan. After median follow up of 14.5 months, the median PFS was 13.4 months (Figure 1), and the median OS was not reached (Figure 2). 4 patients underwent HSCT (3 autologous, and 1 allogeneic). Conclusion: BvB combination is an effective outpatient-based salvage regimen for heavily pretreated patients with multiple lines chemotherapy in relapsed/refractory HL, as majority of patients in our study were beyond first salvage. As there is no standard salvage regimen in this setting, randomized trials are needed to compare efficacy and safety BvB with other established regimens. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: JAK2 GGCC 46/1 haplotype can be represented by four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) which replace one cytosine and three thymidines by two guanosines and two cytosines, generating a "GGCC" combination. These four SNPs located on JAK2 introns 10, 12, 14, and 15, respectively, and are always inherited together, being in complete linkage disequilibrium. The 46/1 component of the name came from Jones et al. study where the haplotype structure of the JAK2 gene was mapped using 14 SNPs genotyped by the Wellcome Trust Case Control Consortium (WTCCC) in 1500 healthy blood donors. Two haplotypes (numbers 46 and 1) were found to be identical except for one SNP, and they have a combined frequency of 0.24 in healthy individuals. Numerous observational studies associate this haplotype with myeloproliferative neoplasms (MPNs), as well as splanchnic vein thrombosis (SVT) and non-splanchnic vein thrombosis (non-SVT). In contrast to 24% frequency noted in healthy population, the frequency goes up to 40-80% in JAK2 V617F mutated MPN, and in 64% of those with JAK2 exon 12 mutations (Anelli et al. IJMS, 2018). We herein report our study of JAK2 GGCC (46/1) Haplotype in unprovoked Venous Thrombotic Events (VTE) in patients with negative thrombophilia workup, including negative JAK2 V617F mutation. Methods: We retrospectively identified patients positive for one of the two SNPs (rs12343867 and rs10974900) and unprovoked venous thrombotic among adult patients with negative thrombophilia workup (including JAK2 mutation) treated at tertiary care center from January 2018 to January 2021. Results: We have identified 8 patients, Table (1), that were positive for JAK2 46/1 haplotype SNPs, of whom 62.5% were homozygous 2/2, 25% heterozygous 1/2, while only 12.5% harbor homozygous 1/1 (a normal variant of JAK2 haplotype). The median age 48.5 years (23-65), and the majority (87.5%) were females. Thrombosis site was noted to be SVT in half of the patients, while non-SVT was noted in the other half (12.5% had cerebral vein thrombosis, 12.5% had deep venous thrombosis, 12.5% had a pulmonary embolism, and 12.5% had jugular vein thrombosis). Half of the patients had more than one site venous thrombosis and the other half had only one site. Around 37.50% of the patients had recurrent venous thrombosis on top of therapeutic anticoagulation. Two patients (25%) had high hemoglobin (17.4/16.7) g/dl, but did not fulfill the criteria for polycythemia vera diagnosis (of whom one is a male smoker and one was a female). None of the patients had leukocytosis or thrombocytosis. By imaging, one patient had mild splenomegaly which could be related to SVT. Conclusion: We report on a potential correlation between unprovoked thrombotic events, mainly venous thrombotic events, with JAK2 46/1 haplotype in patients with a negative thrombophilia workup, a finding that merit further investigation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) 75 years or older, or unfit for intensive chemotherapy. As precision therapy in AML expanded with the addition of venetoclax among others in the therapeutic armamentarium of AML, efficacy and safety reports in ethnic minorities are limited, with a background of well recognized inter-ethnic differences in drug response. Phase III data from VIALE-A, as well as VIALE-C, was limited for the Arab population as no site opened in the Arab world. We herein report our experience on the use of venetoclax with azacitidine in patients with newly diagnosed or relapsed/refractory AML in the Arab population. Methods: Retrospective-single center review on the use of Azacitidine with venetoclax in older patients (aged ≥60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML and relapsed or refractory AML. All patients self-identified of Arabic ethnicity. Patients who received previous BCL2-inhibitor therapy were excluded. Patients who received at least one dose of treatment (Azacitidine ≥3 days, >14 days of venetoclax) were included in the intention to treat analysis. Patients typically received azacitidine 75 mg/m2 intravenously for 7 days with oral venetoclax 400 mg daily for induction, with appropriate dose adjustment for concomitant use of azoles. This is followed by the same regimen in consolidation, with adjustment according to response and side effects at the treating physician's discretion. The primary endpoint was overall survival. The secondary endpoints include response rate, safety, and relapse-free survival. Results: Between July 2019, and July 2021, we identified 19 patients; 13 (68%) had newly diagnosed AML (ND-AML), and 6 (32%) had relapsed or refractory AML (R/R AML). The median age was 70 years (17-82). In the ND-AML, most patients had an adverse ELN 2017 AML (69%) with 23% having either intermediate or adverse AML (Negative for CBF, NPM1, FLT3-ITD and biCEBPA, but missing NGS data for adverse mutations Tp53/ASXL1 and RUNX1). Only one patient was classified as intermediate-risk AML. The overall response rate in the ND-AML was 77%, with 46% achieving complete remission (CR), and 23% CR with incomplete count recovery (CRi) [Table]. One patient achieved PR after the first cycle (blast 7% by morphology and 1.5% by flow cytometry) and did not have a subsequent bone marrow evaluation, however had a full count recovery. Among the responders in the ND-AML cohort, 4 deaths were noted. One death was related to COVID-19 associated pneumonia, one due to graft failure (at day 42 post Haplo-SCT), one due to septic shock, and one was related to relapse disease. The overall survival and relapse-free survival for ND-AML were 5.6 months for both [Figure]. In the R/R AML, 66% had prior HMA exposure, and all patients did receive high-intensity chemotherapy. The median number of prior treatments was 3 (1-5). the response rate was 80% (4/5), with 60% achieving CR. All patients are still alive with a median follow-up of 7.6 months. One patient had progressive disease. One patient is early to evaluate and was not included in the response analysis [Table]. The 30-day mortality was zero in both ND-AML and R/R AML cohorts. Conclusions: In a majority of adverse risk ND-AML, and in heavily pretreated R/R AML, the response rate and overall survival is comparable to what has been previously reported. Our data support the use of this regimen in older patients with newly diagnosed AML, patients with relapsed or refractory disease, and those with adverse-risk features. This analysis is limited by the small number of patients, and by the lack of ELN 2017 favorable-risk AML. Future prospective and randomized studies are needed to clarify activity and safety in the Arab population, as well as in the high-risk AML subset. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

e19562 Background: Central nervous system (CNS) relapse develops in 2-10% of patients with diffuse large B cell lymphoma (DLBCL) and has an adverse prognosis. Tools like IPI and CNS-IPI scores identify patients at high risk of systemic or CNS relapse based on the presence of established risk factors ( Schmitz et al. JCO 2016). International guidelines propose prophylactic intravenous high-dose methotrexate (HD-MTX) for patients at high risk of CNS relapse; however, limited data is backing this approach. Methods: We conducted a retrospective review of newly diagnosed DLBCL patients aged 18-75 years treated with curative intent at large academic medical centers in Riyadh, Saudi Arabia, between 2015-2018. Patients who were planned for CNS HD-MTX after cycles 2, 4, and 6 of R-CHOP and received at least one HD-MTX cycle were included. Results: We identified 35 DLBCL patients who received at least one R-CHOP cycle with one cycle of HD-MTX. The median IPI and CNS-IPI score were 3, (range = 0-4) and 3, (range = 0-5), respectively. The median number of R-CHOP cycles received was 6 (range 3-6) and HD-MTX 3 (range 1-6). The overall response rate was 91%, with 3 (9%) primary refractory patients per interim evaluation on cycle 3 of R-CHOP. Achieving complete remission after six cycles of RCHOP was noted in 80%, with four additional patients showed residual disease at the end of treatment evaluation. The entire cohort's overall survival was not reached, and five years estimated survival is 75%. With a median follow-up duration of 37.3 months, none of the patients relapsed after achieving CR at the end of treatment evaluation. The risk of systemic or CNS relapse in our cohort was 0%. In restricting the analysis to CNS-IPI of ≥ 4, a total of 13 patients with a median follow-up of 42 months were included; four patients did not achieve CR by the end of treatment, while nine patients continue to be in CR without any evidence of relapsed disease. Conclusions: High-dose methotrexate with high-intensity chemoimmunotherapy (R-CHOP) seems to be associated with an improvement in the expected rate of CNS relapse. Our data set is small, and a more extensive study evaluating HD-MTX's effectiveness in high-risk DLBCL is warranted.[Table: see text]

Background: Hematology practice in developing countries has some unique issues including a higher prevalence of infectious disease markers. Epstein-Barr virus (EBV) is an oncogenic virus and implicated in Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma and leiomyosarcoma in the immunocompromised (Ito Y et al. 2009). Cytomegalovirus (CMV) infection/reactivation in patients with hematological malignancies causes serious morbidity and mortality. Saudi Arabia is a high income rapidly developing country, but seroprevalence of CMV and EBV is reportedly higher compared to developed countries (Ghazi 2002, Seale et al., 2006, Joseph et al., 2005). EBV & CMV co-infection is not infrequent & occurs most commonly in the immunocompromised host. A significantly higher prevalence of antibodies (Abs) against CMV & EBV in some disease groups compared to controls has been reported from the same communities (Ocak et al., 2006, Al-Hakami et al., 2016). Interestingly, CMV disease occurrence in sibling donor hematopoietic stem cell transplant (HSCT) is infrequent in our area in spite of the occurrence of CMV reactivations (Aljurf et al., 2009, Saovic et al., 1999). Hence, knowledge of seroprevalence of these viruses in hematological malignancies may be helpful in strategic planning for transplants & transfusions. It may help in establishing any plausible etiological linkage with certain hematological malignancies. Methods: We retrospectively examined the records of adult patients (>14 years) with hematological malignancies for CMV and EBV status (IgG and IgM Abs by chemiluminescence immunoassay). We identified 2,007 patients (1104 males and 903 females) and grouped them according to gender along with broad hematological malignancy categories (Table 1). We tried to establish if any disease category had extraordinary seropositivity for CMV (IgG ≥20 U/ml) or EBV (IgG ≥12 U/ml). We also studied the prevalence of IgM Abs in those tested positive for IgG Abs. Results: Of 2,007 patients (males significantly more than females, p = 0.001), age range 14-93 year (mean 47.2), 503 underwent testing for CMV status and 520 for EBV. Among these tested patients, there was no significant gender difference as 96.1% males were CMV positive, and 95.4% females were CMV positive. On the other hand, 96.9% males were EBV IgG Abs positive compared to 92.5% of females, which was 2.56 (95% CI; 1.12 - 5.96) times more likely to be positive in the studied male patient population (p = 0.021). Overall seroprevalence for CMV IgG Abs was 95.4%, and for EBV IgG Abs it was 95% (Table 1). Among those with CMV IgG Abs, 25/482 (5.1%) had very high antibodies titer (>180 U/ml), and 23/25 patients (92%) had lymphoid malignancies (11 NHL, 7 HL, 2 ALL, 3 MM) and 2 had CML. Among those with EBV IgG Abs 59/495 (11.9%) had very high antibodies titer (>750U/ml); and 46/59 (77.97%) of these patients had lymphoid malignancies (20 HL, 16 NHL, 6 ALL, 4 CLL, 1 MM) and 13/59 (22.03%) had myeloid neoplasms (6 AML, 5 CML, 1 MDS, 1 MPN). Six patients had very high titers for both EBV and CMV antibodies. In CMV IgG Abs positive patients only 1.03% (5/482) had IgM antibodies, and in EBV IgG Abs positive only 2.22% (11/495) had IgM antibodies. Table 1 shows the prevalence across the gender and in different disease categories. The highest seroprevalence for CMV was found in CLL, multiple myeloma and MDS patients (100%); and for EBV it was highest in MDS and MPN patients (100%). Relatively lower seroprevalence of EBV was noted in ALL patients group (86.2%), and lower seroprevalence of CMV was noted in MPN patients group (87.5%). However, overall, there was no significant difference across the disease categories for either CMV (p = 0.362) or EBV (p = 0.114). Conclusions: In this large study on our patients with hematological malignancies, we report very high seroprevalence of CMV and EBV Abs, reaching up to 100% in some disease categories. Among those with very high titer of EBV IgG Abs, the majority had lymphoid malignancies. Short of establishing any etiological linkage, we noticed 100% of MDS patients had both CMV and EBV Abs. Contrary to other reports, our male patients were more likely to be EBV positive compared to the females. Our results support the need for further studies to investigate possible cooperative linkage of EBV and CMV in carcinogenesis. Disclosures No relevant conflicts of interest to declare.