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Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinicaltrials.gov using the terms “selinexor”, “belantamab”, “belamaf”, and “multiple myeloma” without applying any limitations based on the date of the study, language, or country of origin. The most common hematological toxicity associated with these two drugs is thrombocytopenia. Cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia are the major toxicities of Sel. Keratopathy and anemia are the major toxicities of belamaf. Treatment modifications and dose interruption are usually needed when side effects are more than grade II. As these are newer drugs with limited data, continuous surveillance and monitoring are warranted during the treatment course with early mitigation strategies.

Renal cell carcinoma can have lung metastasis even after a long interval of radical nephrectomy (16 years after nephrectomy in our case). If any pulmonary nodule is diagnosed with a history of RCC, pulmonary metastasis of RCC should be suspected and should be appropriately treated.

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50-90% and 50-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jirovecii. PCP due to immunosuppressive drugs is rarely reported in the literature. Herein we present a case of PCP in a 49-year-old patient who presented with progressive shortness of breath, dry cough, and low-grade fever. History revealed that he was taking prednisolone daily for his hyperactive airway disease. His temperature was 99oF, and he had bilateral crackles in the lungs with resonant wheezing. High-resolution computed tomography showed diffuse ground-glass haze and cystic lesions in the middle and upper zones of both lungs. He was commenced on intravenous ceftriaxone and methylprednisolone based on provisional diagnosis of interstitial pneumonia. However, his condition worsened. His human immunodeficiency virus (HIV) test was reactive, and his CD4+ count was 275 cells/mm3. Bronchoalveolar lavage revealed PCP by direct immunofluorescent assay. Additional serum testing revealed marked elevation of beta-D-glucan, consistent with PCP diagnosis due to glucocorticoid use. Trimethoprim-sulfamethoxazole and voriconazole were initiated, and his respiratory symptoms started improving. His respiratory condition improved on day 9, and he was discharged with follow-up.

Pancreatic cancer is one of the most aggressive malignancies of the digestive tract and carries a poor prognosis. The majority of patients have advanced disease at the time of diagnosis. Surgical resection offers the only curative treatment, but only a small proportion of patients can undergo surgical resection. Radiofrequency ablation (RFA) is a well-known modality in the management of solid organ tumors, however, its utility in the management of pancreatic cancer is under investigation. Since the past decade, there is increasing use of RFA as it provides a feasible palliation treatment in the management of unresectable pancreatic cancer. RFA causes tumor cytoreduction through multiple mechanisms such as coagulative necrosis, protein denaturation, and activation of anticancer immunity. The safety profile of RFA is controversial because of the high risk for complications, however, small prospective and retrospective studies have shown promising results in its applicability for palliative management of unresectable pancreatic malignancies. In this review, we discuss different approaches of RFA, their indications, technical accessibility, safety, and major complications in the management of unresectable pancreatic cancer.

A 47-year-old female with a past medical history of morbid obesity and hypertension presented with acute onset dizziness that started while she was at work one evening. She did not have chest pain or dyspnea. She had vital signs within an acceptable range, oxygen saturation of 98%-99%, and was not in acute distress. Examination including the Dix-Hallpike maneuver was unremarkable. Computed tomography angiography (CTA) of the head and neck disclosed bilateral pulmonary embolism without any evidence of cerebral ischemia. CTA chest confirmed the diagnosis of bilateral pulmonary emboli. Importantly, besides the obesity, the patient did not have any other risk factors of pulmonary embolism including recent immobilization, surgery, hormonal therapy or contraceptive use, and personal or family history of thromboembolic disorders. However, she was diagnosed with COVID-19 infection six months back with symptoms not requiring hospitalization. Following further workup for her dizziness and neurology evaluation, in the absence of any other plausible etiology, her presenting symptom was attributed to the atypical presentation of pulmonary embolism. She was treated with heparin in the hospital and discharged on apixaban. Her symptoms had resolved at the time of discharge.

An intense itching localized to dermatomes is a rare symptom of multiple sclerosis (MS). Herein, we report a case of a 45-year-old female who presented with severe itching and tingling sensation, gait disturbance, and bilateral paresthesia for one week. She also had a history of multiple admission in the hospital due to recurrent walking abnormalities and numbness and tingling of both hands associated with intermittent psychiatric symptoms. The neurological examination revealed spastic quadriparesis with lower limb muscles affected more than the upper limbs, numbness, and sensory loss in the upper extremities in the glove and stocking pattern. Magnetic resonance imaging (MRI) revealed multiple small rounded periventricular plaques in both hemispheres and along the long axis of the corpus callosum (fluid-attenuated inversion recovery/FLAIR sequence), and cerebrospinal fluid analysis revealed the presence of oligoclonal bands, suggestive of MS. She was commenced on methylprednisolone and carbamazepine, leading to progressive resolution of her signs and symptoms. She was discharged with monthly natalizumab, and she was doing well on her follow-up.

Introduction: Myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Pregnancy in the presence of MPN increases the risk of thrombosis, hemorrhagic events, pre-eclampsia, progression to myelofibrosis (MF) or acute myeloid leukemia (AML) leading to poor fetal outcome. Methods: We conducted a literature search on PubMed, Embase, Web of Science, and Clinicaltrials.gov using MeSH terms and key words for MPN, PV, and ET from date of inception to January 2021. We excluded studies reporting less than 10 patients and those not in English language. Results: ET studies: How et al. (121 pregnancy (P)/52 women (W)) reported Aspirin (ASA) was protective and was used in 51.2% P (n=62/107) with OR (odd's ratio) of 0.304 (p=0.048; 90% CI 0.102-0.795). Similar benefit of ASA was also reported by Gangat e t al.(2009) (63P/36W ; P loss 21% in 24 patients receiving ASA vs 75% in 12 patients not receiving ASA), Niittyvuopio et al. (40P/16W; live births (LB) in all 13 P treated with ASA or ASA with prior cytoreduction therapy vs 67% complications and 56% loss of P in patients not treated with ASA), Randi et al. (1999) (16P/13W; 7/13 LB occurred on ASA, and only one P was lost on ASA), Bangerter et al.( 17P/9W; 100% P treated with ASA resulted in LB vs 45% LB in P without any treatment, p=0.04), and Pagliaro et al. (15P/9W; ASA monotherapy (n=3/15P) or ASA+ subcutaneous heparin (n=7/15P) resulted in nine LB). Cincotta e t al. (30P/12W) reported 79% LB with ASA or IFN-α vs 38% LB without any treatment (p=0.06). Among the treatment cohort, 5/7 patients on ASA had a LB, and all 4/4 patients on IFN-α had a LB. However, Beressi et al. (31P/18W) reported 4/8 untreated and 10/19 ASA treated P were lost with no statistically significant benefit. Palandri et al. reported 24P/13W treated with IFN-α (n=1), IFN-α + ASA (n=2) and ASA alone (n=9). The LB rate was not influenced significantly with treatment at conception (treated vs. untreated: 8/12 vs. 7/12, P=0.99). Melillo e t al. (122P/92W) reported no benefit with ASA. IFN-α had positive outcomes with 95% LB than patients not receiving IFN-α with 71.6% LB (OR 0.10 (95%CI: 0.013-0.846, p=0.034)). JAK2 mutation was associated with poorer outcomes (OR 6.19; 95%CI: 1.17-32.61; p=0.038). Wright et al. (43P/20W) reported no statistically significant difference between no treatment (n=16/43), ASA alone (n=24/43), ASA+cytoreduction (n=2/43), and low molecular weight heparin (LMWH) (n=1/43) groups. Passamonti et al.( 96P/58W ) reported statistically significant worse outcomes in JAK2 negative patients, no statistically significant benefit in JAK2 positive patients (p=0.05) with ASA and higher complications with conception while on cytoreduction therapy (n=6/13 abortion, n=3/13 pre-eclampsia). ET + Other MPN studies: Gangat et al. (2020) reported (152W ET and 36W PV) that in 95P/55W with ET, 60% pregnancy loss occurred without ASA vs 27% with ASA (p=0.02). All 4/36W with PV who were treated with one or more of ASA, enoxaparin, and hydroxyurea delivered LB, and 50% developed venous thromboembolism. Sokolowska et al. reported 104P/60W with MPN (47 ET, 3 PV, and 10 PMF) treated with various combinations of cytoreduction therapy (IFN-α in 48P, apheresis in 1P and anticoagulation (LMWH+ASA in 10, LMWH alone in 19 and ASA alone in 24P) during the pregnancy with 72.1% LB. Lapoirie et al. stratified 27P/14W (ET 19P/9W, PV 8P/5W) with MPN into high risk (67%) and standard risk and found significant P loss in all high-risk P that did not receive ASA (n=2). Maternal complications occurred in 3 high-risk P that received ASA. 77% of P treated with ASA, LMWH, or both resulted in a LB. Alimam et al. (58W; ET 47, PV 5, PMF 5, MPN-unclassified 1) reported better than predicted outcomes in 88% of women receiving ASA during P, 38% receiving ASA + prophylactic LMWH and 3% receiving ASA + therapeutic LMWH resulting in 58 LB with a P loss rate of 1.7/100 (95% CI; 0.04-9.24). PV studies: Irene et al. (24P/15W) reported a 40% incidence of P loss without antithrombotic therapy vs 10.5 % P loss receiving ASA, LMWH, or both. Willie e t al. divided 32P/14W with PV into two groups (treatment group: 18 P, treated with ASA during P and LMWH for six weeks postpartum; non-treatment group: 14 P) with 72% vs 14% LB respectively. Conclusion: Use of ASA, LMWH and cytoreductive therapy is the existing practice for pregnancies with MPN. However, proper evidence via a RCT is an unmet need. Figure 1 Figure 1. Disclosures Anwer: Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding; Allogene Therapeutics: Research Funding; GlaxoSmithKline: Research Funding.

Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light chain (AL) proteins in tissue. It commonly affects the heart, which correlates with poor prognosis. Disease-modifying therapies aim to suppress the production of abnormal light chains. Daratumumab (Dara) use is associated with a reduction in light chain protein production. Dara is a human anti-CD38 monoclonal antibody approved for the treatment of newly diagnosed and Relapsed & Refractory Multiple Myeloma. AL amyloidosis plasma cells express CD38, and therefore, Dara is an attractive alternative in this setting. This review aims to assess the efficacy and safety of daratumumab in pre-treated AL amyloidosis patients. Methods: We conducted a comprehensive literature search in PubMed, Embase, Medline using MeSH terms and keywords "AL amyloidosis," "daratumumab", and "darzalex" to incorporate the studies published up to July 2020. We included studies assessing the efficacy and safety of daratumumab alone or in combination with other therapies in pretreated AL amyloidosis. After excluding duplicates, non-relevant, and review articles, we selected four prospective and twelve retrospective studies. RESULTS: In our review, data on 482 patients were included. The ages ranged from 35-88 years. The median number of prior therapies was 3 (ranges:2-6), and the most common therapy was bortezomib in 90% of patients followed by immunomodulators in 55% and stem cell transplant in 35%. A total of 260 (54%) patients received Dara monotherapy, 126 (26%) received Dara plus Dexamethasone (d), and 96 (20%) patients received other Dara containing two or three-drug regimens. The time from the diagnosis to the start of Dara therapy varied from 1 to 137 months. 71 % of patients had cardiac, and 62 % had renal involvement. There was a greater than 30 % reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) in cardiac patients responsive to therapy. 1. Daratumumab monotherapy: Dara monotherapy achieved an overall response rate (ORR) of 76% (191/249), complete response (CR) of 30% (69/224), very good partial response (VGPR) of 41% (79/192) and partial response (PR) of 14% (19/140). The overall survival (OS) ranges from 59-100% at 10-12 months were noted. Table 1. 2. Daratumumab+ Dexamethasone: Dara plus d achieved ORR of 81% (86/106), CR of 51% (53/102), VGPR of 29% (18/62), PR of 15% (15/102), and OS of 87% at 24 months. Table 1. 3. Daratumumab with combination regimens: The use of Dara based combination regimens of Dara+pomalidomide (P)+d (36% of patients), Dara+lenalidomide (R)+d (32%) and Dara+bortezomib (V)+d (18%), reported by Abeykoon et al., showed an ORR of 88% (14/16), CR of 19 % (3/16), VGPR of 63% (10/16), PR of 6 %(1/16), OS of 89 % at 10 months and progression-free survival (PFS) of 83% at 10 months. Godara et al. reported an ORR of 100% (9/9) using a combination of Dara and birtamimab. The combination of D+cyclophosphamide (c)+V+d reported by Palladini et al. achieved an ORR of 96 % (27/28), CR of 36 % (11/28), VGPR of 29 % (8/28) and PR of 14 % (4/28).Table 1. The most reported adverse event was infusion-related reactions; grade 3-4 adverse were less than 10 % and mostly related to the heart (heart failure & atrial fibrillation). The most-reported hematological adverse effects were anemia, thrombocytopenia, neutropenia, infections, and sepsis. The most common non-hematological adverse events were heart failure, bronchitis, pneumonia, fatigue, nausea, and diarrhea. Table 2. Conclusion: Dara therapy is associated with promising efficacy with a response rate of more than 70% when used alone and more than 80% when used in combination. These regimens are well tolerated in advanced cardiac disease patients with a tolerable risk of volume overload and infusion-related complications. Additional multicenter randomized, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Light chain amyloidosis (AL) is a plasma cell disorder associated with detrimental manifestations in multiple organ systems of the body. It is estimated that approximately 1275-3200 new cases occur in the United States annually. Proteasome inhibitors (PI), such as bortezomib, carfilzomib, and ixazomib used for multiple myeloma treatment are also used for the treatment of AL amyloidosis. Our aim in this review is to evaluate the efficacy and safety profile of PI-based regimens for the treatment of newly diagnosed AL Amyloidosis (ND-AL). Methods: We conducted a systematic review (following PRISMA guidelines) by completing a comprehensive literature search on PubMed, Cochrane, ClinicalTrials.gov, and Embase on June 23rd, 2020. We were able to identify 901 articles, 325 articles from PubMed, 50 from Cochrane, 23 from Clinical Trials.org, and 253 from Embase. After the screening, we selected 11 published studies (n=436) including 5 phase lll trials, 2 phase I/II trials. Results: Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) with or without Daratumumab (Dara): In a Phase lll trial (ANDEROMADA study), Palldini et al. (2020) studied the efficacy of Dara+ CyBorD vs CyBorD in ND-AL pts (n=28). The addition of Dara to CyBorD showed an improved overall hematological response (ORR) in 96% with complete response (CR) in 54% pts at a median follow up of 17.6 months (Table 1). In a retrospective study by Lim et al. (2017), CyBorD was given to ND-AL pts (n=39) which showed an ORR in 63% with very good partial response (VGPR) in 50% pts. In a retrospective study by Diaz-Pallares et al. (2020), CyBord was given to ND-AL pts (n=34) which showed an ORR in 91% with CR, VGPR, and partial response (PR) in 26%, 26%, and 38% pts, respectively. Progression-free survival (PFS) and overall survival (OS) were reported at 26.7 months and 22 months (P=0.06) respectively (Table 1). Bortezomib, Melphalan, Dexamethasone (BMD): In a phase III trial (EMN-03 study), Kastritis et al. (2020) studied the efficacy of BMD vs MD in ND-AL pts (n=109). Addition of B to MD showed an improved ORR: 81% vs 56% (p=0.001) with CR/VGPR in 53% vs 28% pts. No significant difference in survival outcome was observed. In a phase III trial, Kastritis et al. (2015) studied the efficacy of BMD vs MD in ND-AL pts (n=69). Addition of B to MD showed an improved ORR: 75% vs 53% (p=0.075) with CR/VGPR in 56% vs 42% pts (p=0.277). OS and PFS were also improved in BMD group as compared to control group: 83% vs 72% (p= 0.295) and 61% vs 49% (p=0.079) at 2 years, respectively (Table 1). Bortezomib, Melphalan, Prednisolone (BMP): In a retrospective study by Lee et al. (2014), BMP was given to ND-AL pts (n=19) which showed an ORR in 84% pts with CR, VGPR and PR in 37%, 21% and 26% pts, respectively (Table 1). Induction with B based regimens for ASCT: In a Phase lll trial (HOVON 104), Minnema et al. (2019), studied the efficacy of BD induction prior to HDM/ASCT in pts (n=35) with ND-AL. At 6 months, BD induction prior to HDM/ASCT vs No BD Induction prior to HDM/ASCT showed an ORR: 80% vs 80% with an improved CR: 43% vs 5% and VGPR: 54% vs 51%. In a Phase I/II trial by Sanchorawala et al. (2015), BD induction followed by B-HDM conditioning for ASCT was done in pts (n=27) with ND-AL. ORR at 6 months post ASCT was observed in 100% pts with CR and VGPR in 63% and 37% pts, respectively (Table 1). Induction with B based regimen prior to ASCT vs Upfront ASCT: In a retrospective analysis by Scharman et al. (2017), 53 pts who received ASCT were categorized into 3 groups i.e. Upfront ASCT, induction with B based regimen and induction with other regimens. ND-AL Patients (n=34/53) receiving B based induction vs no induction showed an improved ORR: 94% vs 69% (p=0.04). OS also improved in B based induction as compared to no induction group: 87% vs 77% (p=0.22) at 3 years. PFS at 3 years was 61% vs 69%, respectively (Table 1). Conclusions: PI-based regimens have shown favorable outcomes in the treatment of ND-AL and are effective therapeutic options. The most promising results are observed with CyBorD+Dara. The adverse events associated with PI-based therapy are peripheral neuropathy, anemia, thrombocytopenia, and infections. Further prospective clinical trials are warranted for a broader understanding of the safety and efficacy profile of PI-based regimens and correlation with individual pts characteristics. Table Caption: Table 1: Comparative efficacy and safety of proteasome-inhibitor based drug regimens in ND-AL Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). MPNs can progress to accelerated and blast phase (MPN-AP/BP), defined by blast percentage of 10-19% and ≥20%, respectively, based on IWG-MRT. The therapeutic options, aside from allogeneic hematopoietic stem cell transplantation (Allo-HSCT), are limited. Hypomethylating agents (HMAs), including azacitidine (5-aza) and decitabine, are an effective treatment option for myelodysplastic syndrome and acute myeloid leukemia (AML). They have been used for older adults who are ineligible for intensive chemotherapy. Herein, we did a systematic review to evaluate the efficacy and toxicity of HMAs in MPN-AP/BP. Methods We comprehensively searched multiple databases (PubMed, google scholar, EMBASE, and clinicaltrials.gov), from the inception of the database until April 2020. We used MeSH terms and keywords related to azacitidine, decitabine, and MPN-AP/BP. We included studies that used HMAs as monotherapy on in combination to treat Philadelphia negative MPNs AP/BP and were published in the English language. The initial search yielded 2439 articles. After screening by two reviewers and excluding irrelevant articles, 16 studies were explored in detail. Results Of those studies, nine articles looked at HMAs as monotherapy (five articles for 5-aza and four articles for decitabine). The remaining articles looked at different combinations, including decitabine and ruxolitinib in four studies, 5-aza and ruxolitinib in one study, and ruxolitinib with either decitabine or 5-aza in one study. The combined overall response rate of the 5-aza monotherapy trials was 52/91 (57%), complete response rate (CR) was 26/118 (22.0%), partial response (PR) was 15/118 (12.7%), and hematological improvement (HI) was 18/118 (15.2%). The median overall survival (OS) ranged from 8.4-13.5 months. The combination of 5-aza and ruxolitinib was reported by Drummond et al. with ORR, CR, and PR of 33%, 16.6%, and 16.6%, respectively. Hobbs et al. reported that 1/8 patients receiving HMA (unspecified) achieved CR or CR with incomplete platelet recovery. Four studies reported the use of decitabine alone for the treatment of MPN-AP/BP. Three out of the four studies reported the response rate, and the combined ORR based on these studies was 14/29 (48.3%), CR was 6/42 (14.3%), and PR was 6/41 (14.6%), while the median OS ranged from 6.9 to 9.7 months. The fourth study published by Mascarenhas et al. reported outcomes of decitabine in 6 patients with MF-BP. Three out of six patients treated with decitabine died at 5, 7, and 10 months. The combined ORR of the four studies of the combination decitabine and ruxolitinib was 22/46 (47.8%), CR was 8/67 (11.9%), and PR was 6/46 (13.0%), while median OS ranged from 6.9 months to 21 months. Lancman et al. reported a CR rate of 15% with the use of ruxolitinib with either decitabine (n=26) or 5-aza (n=1). The most common hematological adverse effects reported were thrombocytopenia, neutropenia, anemia, and lymphopenia. The significant non-hematological adverse events were gastrointestinal intolerance (nausea, vomiting, and diarrhea), hypokalemia, and injection site reaction, in addition to infections and bleeding. Conclusion All evidence available for the use of HMAs in Philadelphia negative MPNs-AP/BP is from small series and retrospective analysis. Although they are well tolerated as monotherapy and in combination with other agents like ruxolitinib, they have low CR rates (up to 22% only). The tolerability profile along with familiarity with the drug makes them an attractive option. More effective treatment options with reasonable toxicity profile remain an unmet need in the elderly or frail and unfit patients, who are ineligible for induction chemotherapy and Allo-HSCT. Prospective larger-scale studies are warranted to evaluate the efficacy of HMAs, preferably in combination with novel agents, to achieve higher remission rates with minimal toxicity. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Celgene: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction: Despite multiple treatment options, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor T-cell (CAR T) therapy, a form of adoptive immunotherapy, has shown favorable outcomes in the treatment of hematological malignancies. The B cell maturation antigen (BCMA) which is present on myeloma cells, serves as a valid target site for CAR T cells. Early studies have shown promising outcomes in patients (pts) with relapsed and refractory MM (RRMM). However, CAR T therapy is also associated with multiple adverse effects. The main objective of this review is to evaluate the all grades of CRS and other commonly occurring adverse events (AE) associated with CAR T therapy in pts with RRMM. Methods: A systematic search of databases (following PRISMA guidelines) PubMed, Cochrane, Embase and, clinicaltrials.gov was performed with no restrictions of language and time period. A total of 249 articles were identified initially and after a detailed screening, we finalized 16 studies including 12 phase I and 3 phase Ib/II clinical trials and 1 retrospective analysis for data extraction. Results: Total included trials were 15 and trial-level data collected from 392 pts is summarized in Table 1 and Table 2. Commonly used CAR T regimens for the treatment of MM were bb2121 BCMA, P BCMA 101 CAR, LCAR B38 M, and anti CD19 CAR. Single Target; Anti BCMA CAR T (Table 1) BCMA CAR T, LCAR-B38M: In a phase I trial, Cohen et al. (2019) reported G1&2 CRS in 56% pts (n=25) and G3 CRS in 32% pts when treated with BCMA specific CAR T. Leukopenia, neutropenia, and lymphopenia were seen in 44%, 44% and 36% of pts, respectively. In a phase I trial, Wang et al. (2019) reported G1 & G2 CRS in 47% and 35% pts (n=57), respectively and G3 CRS in 7% pts when treated with LCAR-B38M CAR T. Pyrexia, thrombocytopenia, and leukopenia were seen in 90%, 49% and 30% pts, respectively. In a phase I trial, Chen et al. (2019) reported G1/2 CRS in 58% pts (n=17) and G3 and G5 CRS in 35% and 5% pts respectively when treated with LCAR-B38M. Hepatotoxicity and cytopenia were seen in 100% and 82% pts, respectively. In a phase 1 trial, Brudno et al. (2018) reported G1/2 in 56% pts (n=16) and G3 in 37% pts when treated with BCMA CAR T. Anemia, leukopenia and thrombocytopenia were observed in 68%, 62% and 43% pts, respectively. JNJ-4528, bb2121 In a phase Ib/II trial, Berdeja et al. (2020) reported G1/2 CRS in 86% pts (n=29), G3 and G4 CRS in 3.5% pts each when treated with JNJ-4528 (an LCAR-B38M) CAR T. Neutropenia, thrombocytopenia and leukopenia were seen in 100%, 69% and 59% pts, respectively. In a phase I trial, Berdeja et al. (2019) reported G1, G2 and G3 CRS in 22%, 32% and 5% pts (n=22), respectively when treated with bb2121 CAR T. Neurotoxicity was observed in 22% pts. In a phase I trial, Raje et al. (2017) reported CRS of any grade in 76% pts (n=33) and G3 CRS in 6% pts when treated with bb2121 CAR T. Neurotoxicity, hypotension and hyponatremia were observed in 42%, 15% and 15% pts, respectively. Dual Target CAR T (Table 2) Anti-CD19/BCMA, PF-3135, Dual Target BM38: In a phase Ib trial, Shi et al. (2019) reported G1/2 CRS in 97% pts (n=32) while G3/4 CRS in 3% pts when treated with anti-CD19/BCMA CAR T. Other AE were slight and reversible. In a phase I/II trial, Yan et al. (2019) reported G1/G2 CRS in 86% pts (n=21) and G3/4 CRS in 5% pts when treated with humanized anti-CD19/BCMA CAR T. Neutropenia, Anemia and thrombocytopenia were observed in 86%, 62% and 62% pts, respectively. In a phase I trial, Raje et al. (2019) reported G1/2 CRS in 24% pts (n=17) and G3 CRS in 5% pts when treated with PF-3515 (anti-CD3-BCMA) CAR T. Hepatotoxicity, thrombocytopenia, Neutropenia and pyrexia were observed in 18%, 24%, 18% and 18% pts, respectively. In a phase I trial, Li et al. (2019) reported G1/2 CRS in 62% pts (n=16) and G3 CRS in 25% pts when treated with Dual-target BM38 CAR T. No dose-limiting (>/G3) toxicities were observed at a median follow up of 36 months. Conclusion: CAR T therapy is emerging as a treatment modality for RRMM. With promising initial results, there is evidence for multiple side effects, the most concerning and common one is CRS. The most frequently occurring CRS grade is G 1&2 (requiring symptomatic treatment), but G3 CRS is also reported which can be dose-limiting and life-threatening. Neurotoxicity, hematological abnormalities, hepatotoxicity and pyrexia are the other common side effects Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Background: Clonal plasma cells in multiple myeloma (MM) over express b-cell lymphoma-2 protein (BCL2). Which is the target for venetoclax (VEN). VEN has a promising efficacy and a favorable safety profile in MM patients. This review highlights the efficacy of VEN for the treatment of relapsed refractory (RR) MM. Methodology: We performed a comprehensive database search on four major databases(PubMed, Embase, Cochrane, and Clinical trials.gov). Our search strategy included MeSH terms and keywords for multiple myeloma and VEN, including trade names and generic names, from the date of inception of the database to April 2020.The initial search revealed 782 articles. After excluding review articles, duplicates, and non-relevant articles,we included six studies(four clinical trials and two retrospective studies), which reported an overall response rate (ORR) in RRMM patients. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of VEN. We pooled the results of the experimental arms of included trials using the inverse variance method and logit transformation. Between studies,the variance was calculated using Der Simonian-Laird Estimator. Results: We identified 568 patients from four clinical trials [Moreau et al.2019, the BELLINI trial, (n=291, venetoclax arm= 194, placebo arm= 97)], Costa et al. 2018 (n=42), Kumar et al. 2017(n=66), and Moreau et al. 2017 (n=66)] and two retrospective studies (Kambhampati et al. 2020 (n= 47) and Sidiqi et al.2019 (n=56)). Among which 563 patients were evaluable for the treatment outcomes. One hundred and forty two patients (25%) had t(11:14)mutation. The median age of the patients ranged from 64-66 years, and the median number of prior therapies was ≥2. The median dose of venetoclax ranged from 50 mg/day to 1200 mg/day in dose-escalation cohorts of clinical trials while in the retrospective study by Kambhampati, S et al., the median dose of venetoclax was 800 mg/day. The pooled overall response rate (ORR) for all patients who received venetoclax (n=466) was 57% (95% confidence interval (CI) 0.34-0.77, p Conclusion: VEN is an effective treatment option for relapsed and refractory multiple myeloma patients with t(11:14) translocation. The overall response rate and the duration of response are better in patients with t(11:14). The CANOVA trial is ongoing now to better answer the debatable question of VEN efficacy in t(11;14) MM patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau.

Background: Patients diagnosed with thalassemia major who are transfusion dependant, have iron accumulation leading to iron toxicity and severe impairment in organs like heart, liver and endocrine organs which are highly sensitive to iron toxicity. This makes iron chelation therapy imperative for these patients. Half of the deaths resulting from iron toxicity related complications are attributed to cardiac complications. Iron chelation therapies have not been completely successful to prevent iron toxicity related complications like arrhythmia, cardiomyopathy and heart failure. Higher doses of iron chelation therapies have been associated with various side effects. Studies have shown L-type calcium channel blocker might be able to reduce iron uptake by myocardium. The aim of this meta-analysis is to assess the efficacy and safety of amlodipine to reduce myocardial iron concentration (MIC). Methods: We used PICO framework to do a systematic literature search using four database PubMed, Cochrane, Embase, and Web of Science using keywords, "Thalassemia" AND "Amlodipine" from the inception till July 2020. The initial search showed 90 articles out of which, six randomized clinical trials (RCT) (N= 226) were selected after exclusion of case reports, case series, preclinical trials, review articles, meta-analysis, and trials not providing any information about preventing iron overload in patients with transfusion dependent thalassemia. We extracted the data for myocardial iron concentration (MIC), myocardial T2, ferritin, hepatic iron/liver iron concentration (LIC), liver T2, left ventricular ejection fraction, response rate and adverse effects. DerSimonian-Laird random effects model was used to derive mean differences along with their 95% confidence interval (CI) using comprehensive meta-analysis version 3.0. Results: In six RCT, 96 patients were tested in experimental group and 97 in control group. In five RCT total number of male participants were 45 in experimental group and 54 in control group. 33 patients had splenectomy in experimental group and 41 in control group. The age range was 8 years to 31 years. The myocardial T2 score increased in amlodipine group compared to standard chelation group with significant mean difference estimated to be -0.62 (95% CI: -0.95-0.29, p-value: Conclusion: This systematic review and meta-analysis suggests that addition of amlodipine 2.5-5 mg/day to standard chelation therapy with monitoring for potential adverse effects, could benefit patients with thalassemia major by reducing cardiac iron overload and thus improve survival and quality of life. Future studies are required to study the role of amlodipine in reducing iron overload in endocrine organs that also absorb iron through voltage-gated channels, particularly considering the close association of cardiac siderosis with endocrine complications and the correlation of pancreas and MICs. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cell proliferation leads to complications and death. Daratumumab (Dara) is a humanized IgGk monoclonal antibody that targets CD38- a glycoprotein expressed on plasma cells and malignant cells. Dara has direct anti-tumor effects along with immunomodulatory activities, resulting in clonal expansion of cytotoxic T cells and diminution of immunosuppressive cells. This review highlights the efficacy and safety of Dara addition to the standard of care regimen, tested in Phase III trials, in patients with relapsed refractory MM (RRMM). Methods: We conducted a systematic literature search in four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov) using MeSH terms and keywords for multiple myeloma and Dara including trade names and generic names from date of inception to April 2020. Initial search revealed 587 articles. After excluding review articles, duplicates, and non-relevant articles, we included three phase III trials reporting daratumumab addition to the standard of care regimens for RRMM patients. Results: A total of 1521 patients out of 1533 enrolled patients were evaluated in three phase III randomized controlled trials. A total of 849 patients were evaluated in the Dara group and 684 patients were evaluated in the control group. Catja. C et al. (2019) studied the role of Dara + bortezomib (V) + dexamethasone (d) in RRMM pts (n=498) in phase III trial (CASTOR). Saad Z.U et al. (2019) underlined the efficacy of Dara + carfilzomib (K) and (d) in RRMM pts (n=466) in phase III trial (CANDOR), and Nizar J. Bahlis et al. (2020) studied Dara + lenolidamide (R) + d in RRMM pts (n=569) in phase III trial (POLLUX). The addition of Dara to Vd, Rd, and Kd group was significant in term of overall response rate (ORR): 85% vs 63% (P Addition of Dara to standard care regimen (Vd and Rd) achieved superior outcomes in terms of ORR, PFS and OS, except Kd group, in which only ORR was improved as compared to control group. Combination of Dara plus standard care regimen improved MRD negative status in RRMM patients as compared to standard regimen. Conclusion: Treatment of RRMM with Dara plus standard care therapy (Vd, Rd, and Kd) has shown promising outcomes with improved efficacy and higher negative MRD status, providing a new benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celgene, Millennium Pharmaceuticals,: Honoraria, Research Funding, Speakers Bureau.

e19021 Background: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HCT) characterized by severe multilineage cytopenia in the absence of mixed donor chimerism, relapse, or severe graft-vs-host disease (GVHD). We present a systemic review and meta-analysis aimed to assess the outcomes with stem cell boost (SCB) for PGF in adult allo-HCT patients. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, 752 articles were screened from 4 databases (PubMed, Embase, Cochrane, and Clinical trials.gov) using MeSH terms and keywords for “hematological malignancies”, “hematopoietic stem cell transplantation”, “CD34 antigen(s)” and “treatment outcome(s)” from the date of inception to Jan 2021. After excluding review, duplicate and non-relevant articles, we included 8 studies (1 prospective, 7 retrospective) reporting hematologic complete/overall response rate (CR/ORR), GVHD and overall survival (OS) after SCB for PGF after Allo-HSCT. Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the ‘meta’ package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. Inter-study variance was calculated using Der Simonian-Laird Estimator. Results: We identified 217 patients who received SCB for PGF after allo-HCT. Median age, time since transplant and SCB dose were 48 (37-54) years, 133 (113-450) days and 3.43 (1.7-4.9) million CD34 cells/kg respectively. CR and ORR were 71% (95%CI 0.63-0.77, I216%) and 80% (95%CI 0.74-0.85, I20%) respectively. After median follow up of 41.5 (5-77) months, actuarial survival rate (ASR) was 54% (95%CI 0.48-0.61, I20%). OS was reported from 80% (1y) to 40% (9y) Acute and chronic GVHD incidence after SCB was 17% (95% CI 0.12-0.23, I2=0%) and 17% (95% CI 0.08-0.32, I2=72%, n=197) respectively, and 25% (95% CI 0.14-0.39, I2=63%, n=163) deaths were due to relapse (Table). Conclusions: CD34 SCB improves outcomes after PGF after allo-HSCT with acceptable toxicity profile. However, current literature lacks high-quality randomized evidence and there remains an unmet need for prospective studies to address optimal dosing and manipulation of SCB. Outcomes with SCB for PGF after allo-HCT (n=217).[Table: see text]

e19045 Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication after liver transplantation. This study aims to explore the association of PTLD with the immunosuppression, types of PTLD, clinical presentation, and outcomes. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and 22 studies were included. Results: Data includes 22,235 total patients who underwent a liver transplant, and 449 (2.0%) patients who developed PTLD were studied. Of the 394 patients where gender was reported, 226 were male and 168 were female. Post-transplant EBV status was positive for 63/115 (56%). 11 studies showed that the median time from transplant to the development of PTLD was 33.4 months. Among the histological types of PTLD, the monomorphic B-cell was the most common type with 127/235 (54%) cases, followed by early lesions 25/235, polymorphic 24/235, Hodgkin lymphoma 8/235, and monomorphic T-cell type 7/235. Treatment of PTLD involved reduction or cessation of the immunosuppressive drugs along with chemotherapy surgery and radiotherapy. Mortality data from 13 studies showed 68/259 (31.3%) patients died either due to PTLD or its complication. Conclusions: PTLD is rare but associated with high mortality after liver transplantation. EBV seropositivity is associated with PTLD in the majority of cases. Monomorphic PTLD is the most common type of PTLD after liver transplantation with DLBCL being the most common subtype. Abdominal symptoms and fever are among the most common symptoms. PTLD after Liver transplant a review of studies. [Table: see text]

e20042 Background: Light-chain deposition disease (LCDD) is part of a wide spectrum of plasma cell proliferation disorders. LCDD predominantly affects kidneys by systemic deposition of congo red negative non-fibrillar light chains. Due to the rarity of disease, no prospective data is available, and clear guidelines don’t exist for the treatment. We reviewed data to summarize effective treatment strategies. Methods: A literature search was conducted on PubMed, Cochrane, and ClinicalTrials.gov with final update in November 2020 using terms ‘light chain deposition disease’, ‘therapy,’ and ‘disease management’. Library was manually screened to remove articles on LCDD in transplant kidneys. We identified 63 case reports/series and 11 retrospective studies n=365. Results: Retrospective Studies: 9 studies (n=283) identified various combinations of LCDD and plasma cell dyscrasias given the rarity of idiopathic LCDD. Lorenz et al. reported 6 patients (pts) that received ASCT with MEL preconditioning with 92% improved proteinuria and 95% improved eGFR. Pozzi et al. reported 63 pts (32% idiopathic LCDD, 65% concurrent MM and 3% concurrent CLL) where all pts received a combination of vincristine, doxorubicin, dexamethasone/methylprednisolone. 5/63 patients received ASCT. The median survival was 4.1 years. Bortezomib (V) based regimens: Most experts favor V based regimens to treat LCDD, but no dedicated trials exist. 26 case reports/case series (37 pts) included; 23 pts with idiopathic LCDD and rest with a concurrent disorder. Daratumumab: Milani et al. treated 8 pts with LCDD and concurrent MM with single agent daratumumab who failed at least one regimen. Autologous stem cell transplant (ASCT): 13 case reports/case series (20 pts) identified who received ASCT with melphalan (MEL) conditioning with/without various combinations of chemotherapies before and after ASCT. 14 pts had LCDD, and 6 pts had concurrent clonal cell dyscrasia. Miscellaneous regimens: Various other regimens showed promising results with improved renal functions but not well studied e.g., thalidomide and dexamethasone (Haruyuki et al.). Conclusions: Dedicated clinical trials are difficult given rarity of LCDD but needed. Bortezomib based regimens seem to be good options, ASCT with MEL conditioning is a suitable choice for younger and fit pts.[Table: see text]

e20014 Background: Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of relapsed/refractory multiple myeloma on July 2019 and August 2020 respectively. The toxicity profile of these drugs is a concern since these are approved for use in patients who have already undergone multiple lines of treatment. Methods: Six studies for Sel and two for belamaf were included after a systematic search of PubMed, Embase, Cochrane, and Clinicaltrials.gov. Results: The most common hematological toxicity associated with these two drugs is thrombocytopenia. The common G-3/4 hematological AEs of Sel were thrombocytopenia (39%-71%), anemia (16%-33%), leukopenia (8%-33%) and neutropenia (9%-33%) whereas common G-3/4 non-hematological AEs were hyponatremia (5%-26%), fatigue (13%-15%), diarrhea (5%-10%), eye disorders (9%-10%), musculoskeletal disorders (4%-10%), elevated liver enzymes (10%), peripheral neuropathy (5%) and vomiting (2-4%). Keratopathy and anemia were the major toxicities of belamaf. Most of these toxicities are manageable. Treatment modifications and dose interruption are usually needed when AEs are more than grade II. REMS program guidelines is recommended for close monitoring and evaluation of Sel and belamaf toxicities and early ophthalmological intervention. Conclusions: As these are newer drugs with limited data, continuous surveillance and monitoring is warranted during the treatment course with early mitigation strategies. The physician should be aware of thrombocytopenia and its management as well as belamaf ocular toxicity which is manageable but if missed could have serious complications.[Table: see text]

Introduction: Daratumumab (Dara) is a human anti-CD38 monoclonal antibody approved for multiple myeloma (MM) treatment. Dara has shown promising efficacy and a favorable safety profile in newly diagnosed (ND) and relapsed refractory MM patients. This study is focused on the efficacy and safety of Dara when added to the standard care regimen in transplant eligible newly diagnosed MM (NDMM) in phase III clinical trials. Methods: We performed a comprehensive literature search on four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included MeSH (Medical Subject Headings) terms and keywords for multiple myeloma and Dara including trade names and generic names from date of inception to May 2020. Initial search revealed 588 articles. After a detailed screening, two phase III randomized clinical trials were included, which reported overall response rate (ORR) and negative minimal residual disease (MRD) in transplant eligible MM patients with Dara addition to standard care regimen. Odds ratios (OR) of ORR and MRD were computed along with 95% confidence intervals (CI) for pooled analysis using a fixed-effect model in RevMan v.5.4. Results: A total of 1292 transplant eligible NDMM patients were enrolled and evaluated in two phase III randomized controlled trials. Six hundred and forty-seven patients were in the Dara group and 645 patients were in the control group. Moreau et al. (2019) studied the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) vs VTd in NDMM pts (n=1085) in CASSIOPEIA phase III trial. Vorhees et al. reported efficacy of Dara addition to lenalidomide (R), and Vd vs RVd in GRIFFIN study in transplant eligible NDMM patients (n= 207). Dara dose was 16 mg/kg in both studies and the median follow-up was 18.8 months and 22.1 months in CASSIOPEIA and GRIFFIN trial, respectively. A pooled analysis of these trials showed ORR (OR: 1.73, 95% CI 1.16-2.59; p < 0.008, I2 = 80%). Achievement of MRD negative status was significant in Dara based regimen as compared to control group (OR: 2.47, 95% CI 1.97-3.10; p < 0.00001, I2 = 66%). Dara addition to standard care regimen (Rd and VMP) also decreased the risk of progressive disease (OR: 0.74, 95% CI 0.43-1.28; p < 0.28, I2 = 0%). However, Dara based regimens increased the risk of neutropenia (OR: 3.41, 95% CI 2.68-4.33; p < 0.00001, I2 = 91%), and lymphopenia (OR: 3.43, 95% CI 2.71-4.34; p < 0.0001, I2 = 94%), and pyrexia (OR: 1.42 95% CI 1.11-1.82: p < 0.005, I2=50%) (Figure 1). Conclusion: Addition of Dara to the standard care regimen (VRd, VTd) for transplant eligible NDMM achieved the surrogate endpoints with improved efficacy and MRD negative status with manageable toxicity. However, data from more randomized controlled trials are needed. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: In multiple myeloma (MM), plasma cells including malignant cells show expression of CD38, which is the target for daratumumab (Dara), an IgG1k monoclonal antibody, approved for MM treatment. This review highlights the efficacy and safety of Dara addition to the standard of care therapy in newly diagnosed MM (NDMM) patients (pts). Methods: We conducted a literature search using four databases (PubMed, Embase, Web of Science, and Clinicaltrials.gov). Our search strategy included MeSH terms and key words for multiple myeloma and Dara including trade names and generic names from date of inception to April 2020. A total of 587 articles were screened, and after excluding review articles, duplicates, and non-relevant articles, we included three phase III trials reporting daratumumab addition to the standard of care regimens for NDMM patients. Results: A total of 2528 patients were enrolled and evaluated in three phase III randomized controlled trials. A total of 1261 patients were in the daratumumab group and 1267 patients were in the control group. Total 1085 were transplant eligible and 1443 patients were transplant ineligible. Transplant eligible: Moreau et al. (2019) underlined the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) in NDMM pts (n=1085) in CASSIOPEIA phase III trial. Addition of Dara to VTd group showed marked improvent in progression free survival (PFS): 93% vs 85% at 18 months (hazard ratio (HR) 0.42 [0.34-0.51]; p Bahlis N et al. (2019) studied Dara + lenolidamide (R) and dexamethasone (d) in NDMM pts (n=737) in MAIA phase III trial. Mateos et al. (2018) reported the role of Dara + V + melphalan (M) + prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). Addition of Dara to Rd, and VMP group showed marked improvent in PFS: 68% vs 46% at 36 months [confidence interval [CI], 0.44-0.71; P Significant toxicities mainly included pancytopenias and opportunistic infections (table 2). Standard care regimen (VTd, VMP, Rd) with Dara addition achieved superior outcomes in terms of ORR and PFS. Addition of Dara improved MRD negative status. Conclusion: NDMM treatment with Dara plus standard care therapy (VTd, VMP, Rd) has shown promising outcomes and has set a benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

2562 Background: High dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) has shown to overcome intrinsic chemo-resistance and improve disease control in Primary Central Nervous System Lymphoma (PCNSL). Our study reviews the treatment outcome in PCNSL with sequential HDCT and ASCT. Methods: 8/34 studies were finalized after systematic search of PubMed, Cochrane, and Clinicaltrials.gov for treatment of PCNSL with HDCT followed by ASCT. Results: 251/288 patients were evaluated. Mean age was 55.5 years. 227 underwent HDCT-ASCT. 174 were newly diagnosed (ND) and 77 had relapsed refractory (R/R) PCNSL. ND patients showed superior outcomes in terms of progression free survival and overall survival. Combinations of High dose Rituximab, Busulfan and Cyclophosphamide significantly improved survival outcomes in RR patients. Significant toxicities mainly included pancytopenias and opportunistic. Conclusions: Primary CNS lymphoma treated with HDCT followed by ASCT has shown promising outcomes and has set a benchmark for future studies. [Table: see text]