Introduction: Reactivation of HBV refers to an increase in hepatitis B virus replication in a patient with inactive or resolved HBV. Reactivation of HBV replication has been reported in 20% to 50% of untreated HBV carriers undergoing immunosuppressive or cancer chemotherapy. Bortezomib has been reported to induce viral reactivation(5.9% HBV reactivation rate)(Liu et al). Herein, we aim to present the rate and fate of HBV reactivation among myeloma patients who have received lenalidomide containing protocols. Patients and Methods: We have evaluated 142 MM patients diagnosed between 2003-2014 who received lenalidomide during their treatment schedules whether for induction, relapse or post-induction maintenance treatment. 92 patients received 25 mg/day lenalidomide with Dexamethasone, 50 received at 10 mg/day as single agent. To be eligible for the analysis a minimum three months duration of treatment and no active hepatitis were required. Hepatitis B serology is rechecked before autologous peripheral stem cell transplantation and if liver enzyme abnormality occured. The hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (AntiHBe) are detected by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers are determined by quantitative PCR. Results: The median age of 142 MM patients was 56 (range, 42-77). 79 of patients were male (56%). ISS scores at diagnosis were as follows: ISS I/II/III: 51 (36%),57 (40%), 34 (24%). At the initiation of treatment 11 patients had negative HbsAg, positive AntiHBe, AntiHBcIgG, AntiHBs with normal liver function tests. Lamivudine prophylaxis was administered to these naturally immune 11 patients. One of these eleven patients and five patients who had no prior viral exposure had hepatitis B reactivation (4.2%) (Table). All these patients had hypogamaglobulinemia at diagnosis and had received bortezomib prior to lenalidomide. One patient had a history of dialysis. Four patients had received dexamethasone treatment in addition to lenalidomide. After treatment of tenofovir, HBV DNA titers decreased in all and disappeared among three of the six patients. Lenalidomide treatment was interrupted in three of the patients due to progression of disease. One patient who received a second stem cell transplantation for a secondary refractory disease had a progression to cirrhosis following high dose Melphalan. Conclusion: In the current retrospective analysis we observed reactivation of hepatitis in 4.2% of patients who happened to have high ISS scores and were heavily treated previously. Only one patient had activation under prophylaxis. Lenalidomide can be associated with a low reactivation rate of HBV. Hepatitis B reactivation was detected more with lenalidomide and dexamethasone treated patients. The reactivation rate observed in this retrospective analysis is lower than those published previously and may account for the immune modulation effects of lenalidomide and close follow-up. Table 1. Patient Characteristics (CR: Complete Response, PR: Partial Response, PD: Progressive Disease, VGPR: Very Good Partial Response) Patient Age (years)/MM type/ISS Treatment lines/Bortezomib prior/Lamivudine prophylaxis Hepatitis B markers at diagnosis Hepatitis B markers after revlimid treatment Treatment/Time to reactivation after lenalidomide (months) OS (months)/Status of disease 56/Lambda/2 3/+/- HBsAg-, HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg, AntiHBc+,AntiHBS- Tenofovir/11 20/CR 74/ IgGkappa/2 4/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/18 52/PR 45 /IgGkappa/3 4/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBs- Tenofovir/16 58/VGPR 61/ IgGkappa/3 5/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/13 45/VGPR 43/IgAlambda/3 6/+/+ HBsAg-,HBeAg-AntiHBeAg+,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/7 58/PD 67/ IgGkappa/3 5/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/12 66/PD Disclosures No relevant conflicts of interest to declare.

Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre’s experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x10 9 /l (1-23), which increased to 41x10 9 /l (6-150). The median platelet count increment was 29.5x10 9 /l ( p = 0.001). The pre-treatment median neutrophil count was 1.19x10 9 /l (0.39-5.1), which increased to 2.35 x10 9 /l (0.1-5.33) ( p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl ( p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Introduction: A vast majority of multiple myeloma (MM) patients requires subsequent lines of therapy following relapses. The choice of regimen following relapse is influenced by response, tolerance to prior therapies, as well as by disease and patient features. Treatment options are limited for those who develop triple-class refractory disease. In this setting, the role of a salvage autologous stem cell transplantation (sAHCT) is controversial. This unmet need has driven the development of new therapies with novel mechanisms of action. Selinexor, an oral selective inhibitor of nuclear export (SINE) compound, was recently approved by the FDA and EMA for use in heavily pretreated relapse refractory (RRMM) patients, including triple-class refractory RRMM and FDA has also approved the agent in patients with first relapse. In the absence of head-to-head studies, comparison of treatment options among triple-class treated patients is based on real world experience. Here we performed a retrospective comparison between outcomes following sAHCT versus Selinexor combinations administered among RRMMs. Patients & Methods: Between January 2015 and April 2021, 22 patients at our center underwent sAHCT for treatment of refractory relapse. A transplant was defined as salvage if the patient had already received one prior AHCT and underwent a further AHCT after evidence of disease progression not responding to second generation proteasome inhibitors (PI), İmmunomodulating agents (IMID) or antiCD38 monoclonal antibody. We compared the outcomes of these patients with 10 RRMM patients who had exhausted their treatment options and were progressing on their last line of therapy to receive Selinexor, dexamethasone in combination with either bortezomib (n=7) (XVd) or carfilzomib (n=3) (XCd) as a part of a Karyopharm Expanded Access Program (KEAP). Selinexor was administered 80-100 mg po weekly in combination. Response and disease progression were assessed according to the IMWG criteria. Results: Patients' characteristics and the outcome of treatments are shown in Table. The median age of patients was similar in both groups. Patients were heavily treated with a median of 6 prior lines of therapy (4-9) and 2 out of 10 carried high-risk cytogenetics in SVd group. Seven (31.8%) patients with high-risk cytogenetics underwent sAHCT. All patients were treated with or refractory to immunomodulators and proteasome inhibitors. Five patients responded to DCEP bridging therapy prior to sAHCT. Five patients received Selinexor after sAHCT. One patient underwent sAHCT due to progression under Selinexor treatment. In sAHCT group, 68.2% of patients relapsed within a median of 6.3 months (Figure-1). Figure-2 shows the impact of the prior lines of therapy and selinoxor on PFS.Adverse events on selinexor regimens included fatigue, nausea, thrombocytopenia which were managed with Selinexor dose adjustment and supportive care. Two patients eventually transitioned to new therapies, while 4 still remain on SVd due to continued response. Conclusion: Our results based on a small number of patients, compared with outcomes post sAHCT reflects comparable duration of response and disease control rates with Selinexor-PI regimens among selected patients. Hospitalization and prolonged infusions are not required with the selinexor regimens, and prolonged treatment is possible with advance in lines of therapy duration of response lessens with any treatment modality. Despite of a DCEP bridging therapy prior to sAHCT, Selinexor combos have achieved similar PFS even among triple class refractory MM patients. For countries where CAR-T therapies are not accessible, sAHCT and Selinexor combinations may be considered as a valid clinical option after failing CD38 monoclonal antibodies, PI and IMIDs. These data support the use of selinexor-based regimens in the treatment of relapsed MM, and given the potency of the combinations, in earlier lines of therapy including in patients who have received anti-CD38 mAbs. Figure 1 Figure 1. Disclosures Kashyap: Karyopharm: Current Employment. Niblock: Karyopharm: Current Employment. Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau. OffLabel Disclosure: Selinexor has not been approved for myeloma patients in Turkey. It could be used as a part of Karyopharm Expanded Access program (KEAP).

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