Introduction: Waldenström's macroglobulinemia is a rare low-grade lymphoplasmacytic lymphoma characterized by CD20 expression on malignant cells and produces a monoclonal immunoglobulin M (IgM). Rituximab is a chimeric monoclonal antibody against CD20 antigen and the most widely used therapeutic agents in WM. Rituximab works by adhering to CD20, causes B-cell lysis mainly through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. Cyclophosphamide is an alkylating agent binds to DNA. Its cytotoxic effect is mainly due to cross-linking of strands of DNA and RNA, and to inhibition of protein synthesis. Our objective is to analyze and summarize the published literature for the efficacy of regimens containing both rituximab and cyclophosphamide for the treatment of Waldenström's macroglobulinemia (WM). Methods:We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after January 2005, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library, and Web of Science. A total of 585 articles were identified initially, and after a detailed screening, we finalized 10 studies involving 425 WM patients. Results:The total number of patients were 425. The dose was 375 mg/m2. The complete response (CR) ranged from 3-19%, very good partial response (VGPR) ranged from 4-22%, and the partial response (PR) ranged from 8-82%. The overall response rate (ORR) ranged from 79-95%. Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP): In a retrospective study by Ioakimidis et al., included 23 WM patients were given R-CHOP. The ORR was 95%, with 69% achieving a major response, 43%, PR, and VGPR OF 9%. In a randomized control trial by Buske et al., N=23, the major response rate was 91%, and PR was 82%. Treon et al. (N=13) observed a major response rate of 27%. (Table 1). Fludarabine, Cyclophosphamide and Rituximab (FCR): In a retrospective study by Peinert et al., involving 29 patients receiving the FCR regimen, the ORR was 90%, with 79%, 3%, and 10% of patients achieving PR, CR, and NR, respectively. In a study by Tedeschi et al., involving 40 patients, ORR was 80%, and the major response rate was 80%. Souchet et al., N=82 reported an ORR of 84% and a PR of 46%. Progression-free survival (PFS) was 51.2 months for Tedeschi et al. Dexamethasone, Rituximab and Cyclophosphamide (DRC) In study Paludo et al., (N=50), receiving the DRC regimen, the highest ORR was 87%, PR 64%, and major response was 68%. In a phase II study by Dimopoulos et al., (N=72), the ORR of 82% and PR of 67% was observed. PFS was 24 months in this study. (Table 1) 4.Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) In study Ioakimidis et al, N=16, the ORR was 87%, the major response rate was 62%, and the PR was 43%. Rituximab, Cyclophosphamide, and Prednisone (RCP) Ioakimidis et al., reported 19 patients who were given RCP. The ORR, PR, and the major response rate was 94%, 73%, and 73%, respectively.Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone (LR-CD) A study by Rosenthal et al., 15 patients were given LR-CD. ORR was 80%, with a major response rate in 80% and PR in 73% of patients. PFS was 38 months. Conclusion: Rituximab and cyclophosphamide, in combination regimens for the treatment of WM showed the overall response rate of 95%. Neutropenia was the dominant side effect reported in these regimens. There is a paucity of phase 3 randomized trials demonstrating a clinical benefit of anyone regimen over another. We recommend future randomized prospective trials better to understand the efficacy and safety profile of regimens containing both rituximab and cyclophosphamide base combinations. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

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Methodology: Large lip defects secondary to benign or malignant tumors which could not be closed primarily or involving more than one tissue layer were included. Patients with history of trauma or thermal injuries were excluded. Results: Twelve patients were included in the study. Mean age group was 57.4 years (34 to 75); male to female ratio 1.4: 1; oral commissure tissue deficiency (5 cases) was corrected with cheek advancement and rotation flaps; upper lip defects (3 cases) were reconstructed with cheek advancement and lip switch flaps; for lower lip repair (4 cases), Karapandzic flaps were the primary flaps utilized. Overall complication rate was 16.6%. Partial wound dehiscence was seen in one patient (8.3%). Significant microstomia requiring surgical correction was experienced in one patient. Conclusion: Lip reconstruction of acquired defects can be achieved with good functional results by proper planning and judicious use of remaining lip and local cheek tissue.

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.