Patients Receiving Maintenance Therapy Research Articles

Pediatric Vulvar Lichen Sclerosus: A Survey of Disease Course.

To assess long-term outcomes of lichen sclerosus (LS) in the female pediatric population, specifically in relation to patient age, treatment type and duration, and remission. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Retrospective chart review was conducted to identify female pediatric patients (0-18 years of age) who were diagnosed with LS between January 1, 2015 and January 1, 2020 at the University of North Carolina Dermatology and/or Obstetrics and Gynecology Departments. Patients were contacted via telephone for follow-up interviews consisting of a series of questions regarding patient age, symptom onset, time of diagnosis, treatment, and current symptoms. Of the 128 patients identified, 61 patients consented and participated in follow-up interviews. At the time of study follow-up, 55/61 (90%) of participants reported their symptoms were improved. Patients reported using a variety of treatments, with medium- to high-potency topical steroids being the most common. At the time of follow-up, 53/61 (87%) of patients reported being asymptomatic, 37/53 (70%) of whom were not using any form of maintenance therapy. Those who achieved symptom resolution did so at an average of 8.4 years of age. There was no significant difference in age in asymptomatic patients receiving maintenance therapy and those receiving no maintenance therapy. There was a positive correlation for the duration of LS treatment and time in remission (P < .001). Increased patient age at time of follow-up also correlated positively with time in remission (P < .001). In our cohort, the need for continued maintenance therapy was not correlated with age or, by proxy, pubertal status. Thus, LS remission might be determined more by early and successful pharmacological interventions.

Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis

BackgroundWe previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy.MethodsThe relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study).ResultsIn the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA 6 months after the initiation of remission-induction therapy than in patients in remission. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months.ConclusionWe herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.

503 - Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

503 - Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Clinical and microbiological effects of adjunctive local delivery of minocycline (Periocline®) in patients receiving supportive periodontal therapy: a pilot study.

PurposeThis study aimed to evaluate the clinical and microbiological efficacy of adjunctive local delivery of minocycline (Periocline®) in patients receiving supportive periodontal therapy (SPT) after initial treatment.MethodsThe participants were 16 men and 8 women (age, 20–65 years) who had at least 15 natural teeth, underwent SPT for more than 1 year due to chronic periodontitis, had 4 or more periodontal pocket sites deeper than 5 mm, and showed >25% gingival bleeding on probing (BoP). They were randomly assigned to the test and control groups. In the test group, mechanical debridement and local antibiotic delivery were performed for all periodontal sulci/pockets; in the control group, mechanical debridement and saline irrigation were performed. In patients who underwent SPT for more than 1 year, clinical and microbiological examinations were performed at baseline and 1 and 3 months after SPT. The clinical examination included an assessment of the periodontal pocket depth, clinical attachment level, plaque index, and BoP. Microbial tests were performed using real-time polymerase chain reaction; the relative ratios of Porphyromonas gingivalis and Fusobacterium nucleatum were determined.ResultsBoth groups showed significant improvements in clinical parameters at 1 and 3 months from baseline; there were no significant changes between months 1 and 3. Intergroup differences were insignificant. The microbiological analysis revealed no significant differences in P. gingivalis and F. nucleatum ratios across time points. While intergroup differences were insignificant, there was a tendency for the P. gingivalis and F. nucleatum ratios to decrease in the test group.ConclusionsMechanical debridement in patients receiving maintenance therapy resulted in clinically significant improvement; the effectiveness of additional local delivery of antibiotics was not significant. The ratios of P. gingivalis and F. nucleatum showed a tendency to decrease in the test group, although it was not significant.

Adjuvant intravesical chemotherapy with titanium glycerosolvate aquacomplex versus BCG therapy in patients with high risk nonmuscle-invasive bladder cancer

Objective: to compare recurrence rate, progression rate and recurrence-free survival in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after adjuvant intravesical chemotherapy (IVCT) with titanium glycerosolvate aquacomplex (TGA) versus intravesical BCG therapy.Material and methods. In a retrospective multicenter clinical study initially were included 126 patients with NMIBC. Of all 126 patients, 94 patients with high-risk NMIBC were selected and divided into 2 groups using a pseudo randomization with propensity score matching to minimize systematic differences in the process of forming groups. The treatment group (n = 55) consisted of patients with high-risk NMIBC who received a 6-week course of adjuvant IVCT with TGA. In the control group (n = 39) patients received an induction 6-week course of adjuvant intravesical BCG therapy, 19 (49 %) of 39 patients received maintenance therapy. Both methods were compared according to recurrence rate, progression rate and recurrence-free survival. Significance of difference was set at p &lt;0.05.Results. The compared groups of patients were well balanced in terms of clinical and morphological characteristics and the main risk factors for recurrence and progression of non-muscle-invasive bladder cancer, no significant differences were found between the groups (p &gt;0.5). The recurrence rate in treatment and control groups was 33 % and 23 %, respectively (p = 0.31). The disease progression was observed in 1 (2 %) patient in the treatment group and in 4 (13 %) patients in the control group (p = 0.08). The median disease-free survival in both groups of patients was not reached at the time of analysis. Three- and five-year recurrence-free survival in the treatment group of patients were 71 % and 62 %, respectively; in the control group — 76 % and 72 %, respectively. There were no significant differences between recurrence-free-survival curves of the treatment and control groups (p = 0.58).Conclusion. Adjuvant IVCT with TGA has demonstrated a clinical effectiveness comparable to intravesical BCG therapy and it can be used as an alternative method of treatment in patients with high-risk NMIBC.

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Minimal Residual Disease in Autografts and Bone Marrow of Patients with Multiple Myeloma: 8-Color Multiparameter Flow Cytometry (EuroFlow-NGF) Vs. Next-Generation Sequencing

Background: Autologous stem cell transplantation (ASCT) in conjunction with novel therapeutic drugs can dramatically improve response rates and the prognoses of patients with multiple myeloma (MM). However, most patients with MM ultimately relapse due to minimal residual disease (MRD). Next-generation multiparameter flow cytometry (MFC) (EuroFlow-NGF) and next-generation sequencing (NGS) are currently the standard methods to assess MRD. Aims: To compare the prognostic value of MRD detection in autografts and bone marrow (BM) cells using 8-color MFC (EuroFlow-NGF) and NGS (Adaptive Biotechnologies), and also MRD levels between fresh and cryopreserved autografts using NGF. Methods: The study enrolled 52 newly-diagnosed MM patients who underwent ASCT. The median age ASCT was 61 (range 41-69) years and included 29 males and 23 females at ISS I (n = 17), II (n = 23), and III (n = 12). Of these, 18 patients harbored high-risk chromosomal abnormalities including t(4;14) (n = 15), del17p and t(4;14) (n = 2), and complex (n = 1). Bortezomib-based chemotherapy was used for induction together with melphalan at 140 mg/m2 (n = 1) and 200 mg/m2 (n = 51) for conditioning before ASCT. 39 of 52 (75%) patients received maintenance therapy until progressive disease. The best responses achieved post-ASCT included 30 sCR, 4 CR, 15 VGPR, and 3 PR. Forty autografts, one from each MM patient, were analyzed using NGF and NGS protocols, and BM cells at pre/post-ASCT and autografts derived from 16 patients were analyzed using NGS. The EuroFlow-NGF method uses standard sample preparation; large numbers of cells are evaluated using an optimized 8-color antibody panel that facilitates accurate identification of discrimination between phenotypically aberrant plasma cells (aPCs) and their normal counterparts (Flores-Montero et al., Leukemia 2017). NGS-based MRD assessment was performed using Adaptive's standardized NGS-MRD Assay (Seattle, WA) (Martinez-Lopez et al., Blood 2014). Eight additional autografts were used to assess MRD in both fresh and cryopreserved samples by NGF. Results: MRD was evaluated in 48 of 52 autografts (92%) using NGF and in 44 of 52 autografts (85%) using NGS. We identified aPCs in autografts based on multivariate analysis of individual cell populations (e.g., CD56+, CD19−, CyIgκ+, and CD117+). As the results of NGF revealed a strong correlation with respect to MRD in fresh vs. thawed autografts (r = 0.999, P &amp;lt; 0.0001), MRD was subsequently evaluated in thawed autografts. The sensitivity of NGF was 1 × 10−5-2 × 10−6; the sensitivity of NGS was 1 × 10−6. 28 of 48 (58%) of the autografts were MRD-positive by NGF; 30 of 44 (68%) of the autografts were MRD-positive by NGS. MRD levels in autografts using NGF and NGS correlated with one another (r = 0.69, P &amp;lt; 0.0001; Fig. 1A). MRD negative in autografts by NGF cases (MRDNGF (-)) and MRDNGS (-) tended to show better progression-free survival (PFS) than MRDNGF (+) (P = 0.195) and MRDNGS (+) (P = 0.156), respectively. Furthermore, MRDNGS (-) showed significantly better overall survival (OS) than MRDNGS (+) (P = 0.03) (Fig. 1C) while MRDNGF (-) showed better OS than MRDNGF (+) (P = 0.09) (Fig. 1B). Our data revealed only a minimal correlation between MRD in the autografts (median 1.1 × 10−5,range 0-7.29 × 10−4) and in the BM cells at pre-ASCT (median 5.05 × 10−3,range 6 × 10−6-2.64 × 10−1; r = 0.09, P = 0.7) or at post-ASCT (median 2.11 × 10−4,range 0-9.09 × 10−3; r = 0.14, P = 0.6); MRD detected in the autografts was &amp;gt; 27 times lower than that detected in pre-ASCT BM cells, and MRD detected in the post-ASCT BM cells was &amp;gt; 3 times lower than that detected in pre-ASCT BM cells except for one case in which the ratio was increased by two times. Interestingly, while MRD was detected in all BM cells at pre-ASCT (n = 16), 4 of 16 (25%) of these autografts were MRDNGS-negative. The median of MRD levels of the 4 cases in pre-ASCT and post-ASCT BM cells were 4.14 × 10−4 (range 6-583 × 10−6)and 1.8 × 10−5 (range 0-27 × 10−6), respectively. Conclusion: Although EuroFlow-NGF is a rapid and accurate method for detecting MRD, NGS was more sensitive and provided greater prognostic value than EuroFlow-NGF. Disclosures Takamatsu: Adaptive Biotechnologies: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Janssen Pharmaceutical: Consultancy, Honoraria, Research Funding; Ono pharmaceutical: Honoraria, Research Funding; SRL: Consultancy, Research Funding. Takezako:Bristol-Myers Squibb: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding; Abbvie: Research Funding. Nakao:Symbio: Consultancy; Kyowa Kirin: Honoraria; Alexion: Research Funding; Novartis: Honoraria.

Outcomes after Autologous Stem Cell Transplant in Patients with Relapsed Multiple Myeloma

Outcomes after Autologous Stem Cell Transplant in Patients with Relapsed Multiple Myeloma

Novel Insight into Multi-Hit Multiple Myeloma Based on “Two-Hit” Theory of Cancer Causation

Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.

The Real-Word Treatment Outcome of Symptomatic Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia in Chinese Patients

Objective:lymphoplasmacytic lymphoma/Waldenström Macroglobulinemia(LPL/WM) is a rare and incurable lymphoid malignancy. The treatment outcomes in Chinese patients had never been studies. In this study, we systematically reviewed the treatment outcome in a consecutive cohort from a single center in the past 20 years to explore the efficacy of different treatment regimens in real word in China. Methods:The clinical data of 269 newly diagnosis patients with LPL/WM admitted to our hospital in the past 20 years (2000-2020) were retrospectively analyzed. Therapy efficacy and survival were compared between different groups. Results:The median age of 269 patients was 62 years (range 32-87) and the male to female ratio was 2.7(196/73). Nearly half patients were high risk group of ISSWM (48%). Of 269 patients,192 patients received combined chemotherapy.The most common symptoms for initial chemotherapy wereanemia(75.7%), thrombocytopenia (36.9%), followed by IgM-related (33.7%) and constitutional symptoms(21.2%).Of the 192 patients, 109 patients received the novel agents for first-line therapy,83 patients received traditional chemotherapy.180 of192 patients would evaluated. The overall response rate(ORR) and major response rate(MRR) in the novel agent group were significantly higher than the traditional group(ORR:81.7% vs 61.8%,P=0.003; MRR:68.3% vs 48.7%,P=0.008) .In the traditional group, 41 patients received oral alkylating agent-based therapy and 42 patients received conventional intravenous cytotoxicity agents-basedtherapy. The ORR and MRR in the intravenous group were higher than oral group(ORR:75% vs 47.2%,P=0.013;MRR:62.5% vs33.3%,P=0.011).With a median observation time of 36 months, the median overall survival (OS) and progression-free survival (PFS) were 60 months and not reached in the novel agent groups which were also significantly higher than traditional groups(PFS: 60 vs 42,P=0.009,OS:NR vs 89,P=0.000). Intriguingly, In the traditional group, the PFS and OS were no significantly differentbetween conventional intravenous and oralgroup(PFS oral vs intravenous: 42 vs 40,P=0.849,OS oral vs intravenous:62vs 114,P=0.260). In novel agent group, 36 patients had received RCHOP regiment,20 patients received DRC,21 patients received BCD,8 patients received BRD,16 patients received TCD and 8 patients received RFC regiment. Patients who received RCHOP,DRC,BCD,BDR or RFC had similar ORR (82%-87.5%)which were slightly higher than TCD (58.3%)regiment. The median PFS and OS in different subgroups were also similar. But BDR regiment showed a trend of better OS(5 year 100%) and TCD showed a worse OS(5 year 46.4%). For all the patients, 35 patients received maintenance therapy, including 16 patients with rituximab maintenance and 19 patients with thalidomide maintenance. Maintenance was associated with better PFS(60 vs 47,p=0.083) and OS(5 year OS were 96.3% and 64.8%,p=0.006) and patients who received rituximab maintenance had better survival than thalidomide maintenance. In novel agent subgroup, maintenance with rituximab also had a trend of better PFS and OS. But maintenance thalidomide had no significantly different with no maintenance group. Conclusion:Combined with novel agent can tremendously improve the short-term and long-term therapeutic effects in Chinese LPL/WM patients. Different novel agent regiment might had similar efficacy, BRD regiment had a trend of better survival. Maintenance with rituximab would further improve the effect even in novel agent age. Disclosures No relevant conflicts of interest to declare.

Emotional and social well-being in ovarian cancer patients on maintenance versus surveillance

While current data suggest that many ovarian cancer (OC) patients may have a benefit in progression free survival from maintenance therapy after completing primary treatment, little is known about the effect of this therapy on quality of life (QOL) as compared to surveillance. The purpose of this study is to determine differences in QOL symptoms in OC patients receiving maintenance therapy compared to patients in surveillance.

Feasibility of and associated cost savings from transitioning to therapeutic biosimilar use in a large community oncology network.

9 Background: The use of biosimilar drugs in the treatment of cancer offer an opportunity for oncology providers to decrease total cost of care while preserving quality. However, it remains unclear whether providers and patients may resist biosimilar use due to concerns over safety and efficacy. Our national network of 5 practices with over 100 clinics committed to a conversion to therapeutic biosimilars for trastuzumab and bevacizumab after their introduction in July 2019. Methods: Common steps to foster therapeutic biosimilar conversion included frequent communication from medical directors to providers and staff, incorporation of biosimilars into default treatment regimen orders, providing clinical teams lists identifying candidates for conversion, and tracking reasons why biosimilar switch did not occur. Most practices prioritized converting patients initiating new treatments, then later transitioning patients receiving maintenance therapy. This phased approach was taken to ensure that prior authorization and patient consent could be obtained prior to conversion. Rates of biosimilar use were calculated by comparing the number of administrations for which a biosimilar was given to the total number of administrations for which a biosimilar could have been given. Cost savings were calculated by comparing the difference in Medicare allowed rates for each originator and biosimilar drug pair at the time of administration. Results: Biosimilar use increased over time at all practices, from 0% to an average of 67% for trastuzumab and 78% for bevacizumab. The decrease in cost attributed to the use of biosimilars in the study period totaled over $4.4 million. Challenges to biosimilar use included physician preference for the originator drug, difference in preferred agents across payers, and challenges with biosimilar drug storage. Patients rarely had concerns over efficacy and safety. Conclusions: Therapeutic biosimilar adoption in a large oncology network is feasible and can lead to significant cost savings. [Table: see text]

Vagus Nerve Stimulation in Patients Receiving Maintenance Therapy With Electroconvulsive Therapy: A Series of 10 Cases.

Electroconvulsive therapy (ECT) is a mainstay in both acute and long-term management of difficult-to-treat depression. However, frequent acute courses of ECT or prolonged maintenance ECT treatment may increase adverse-effect burden and/or reduce patient acceptability. Therefore, we investigated the effectiveness of adjunctive vagus nerve stimulation (VNS) therapy as an alternative strategy for long-term maintenance treatment in ECT-responsive patients. This retrospective chart review identified maintenance ECT patients with unipolar (n = 5) and bipolar depression (n = 5) from 2 large hospital systems who had a history of ECT response, but the patients had significant residual incapacitating symptoms or increasing concerns regarding the burden associated with ECT and opted to receive adjunctive VNS therapy. The patients were followed for 2 years after VNS implantation. Response and remission were defined as Clinical Global Impression-Severity scale scores of ≤2 and 1, respectively, obtained at 1- and 2-year postimplantation compared with just before VNS implantation. One-year postimplantation, 6 of 10 had responded of which 5 met remission criteria. All 10 patients benefited from adjunctive VNS therapy with either fewer hospitalizations and/or ECT sessions. Seven of 10 stopped maintenance ECT by the end of year 1; an additional patient stopped maintenance ECT by year 2. No patients required an acute course of ECT during the 2-year follow-up. There was a statistically significant reduction (P < 0.0001) in mean (SD) Clinical Global Impression-Severity scale scores between baseline (5.4 [0.51]) and the 1-year postimplantation (2.1 [1.37]) time points, and between baseline and the 2-year postimplantation (2.3 [1.16]) time points, whereas no difference existed between the 1- and 2-year postimplantation time points. Vagus nerve stimulation therapy may be a useful maintenance strategy in patients with difficult-to-treat depression receiving maintenance ECT.

Cost-effectiveness of tofacitinib for the treatment of moderate to severe active ulcerative colitis in Greece.

To evaluate the cost-effectiveness of tofacitinib versus other treatment options currently available for the management of adult patients with moderate-to-severe ulcerative colitis, who have had an inadequate response, loss of response, or were intolerant to conventional therapy or a biologic agent, in Greece. A Markov model was adapted for projecting lifetime costs and outcomes, for a cohort of patients with moderate-to-severe ulcerative colitis from a Greek payer perspective. Patients entered the model in the active ulcerative colitis state and transitioned to a remission or response state or they underwent colectomy. Following an initial 8-week induction treatment period, patients received maintenance therapy until loss of response. Nonresponders could switch to up to two subsequent biologic lines. Clinical efficacy, adverse event rates and utilities derived from OCTAVE trials and a network-meta-analysis (NMA), while adverse event-related disutilities were obtained from the literature. Information on treatment pathways and resource use was provided by an advisory board due to a lack of local data. Unit costs derived from official national sources (€, 2018). Over a life-time horizon, treating moderate-to-severe active ulcerative colitis with tofacitinib resulted in additional quality-adjusted life-years (QALYs) and lower total costs compared to vedolizumab (0.018; €6408), infliximab (biosimilar) (0.009; €3031), golimumab (0.042; €1988) and infliximab (originator) (0.009; €6724). Hence, tofacitinib was estimated to be dominant over all comparators. The results of the analysis suggest that in the Greek setting, tofacitinib could be considered a cost-effective (dominant) treatment option for the treatment of patients with moderate-to-severe active ulcerative colitis.

Maintenance therapy in transplant ineligible adults with newly-diagnosed multiple myeloma: A systematic review and meta-analysis.

The role of maintenance therapy in transplant ineligible multiple myeloma (MM) patients following a period of fixed duration induction therapy remains unclear. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) examining maintenance therapy compared to observation. We conducted a comprehensive search including MEDLINE, Embase, and the Cochrane database up to February 28, 2020, for RCTs comparing maintenance therapy to observation in newly diagnosed transplant ineligible MM patients. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. We performed meta-analyses using a random-effects model and assessed certainty using GRADE methodology. We included five RCTs with a total of 1139 patients. Patients receiving maintenance therapy had improved progression-free survival (PFS) compared to observation (Hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.38 to 0.62, high certainty); however, there was no difference in overall survival (HR 0.96, 95% CI 0.76-1.2, moderate certainty). Adverse events were higher in the maintenance group compared to observation (very low to moderate certainty). Maintenance therapy increases PFS in transplant ineligible MM patients following a fixed period of induction therapy; however, this must be weighed against the increased risk of adverse events.

P0446OUTCOMES OF CYCLOPHOSPHAMIDE FOR ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES-ASSOCIATED VASCULITIS: DIFFERENT PROTOCOLS, SINGLE-CENTER EXPERIENCE AND LITERATURE REVIEW

Abstract Background and Aims Cyclophosphamide (CYC), associated with corticosteroids has been considered the mainstay of treatment for severe antineutrophil cytoplasmic antibody−associated vasculitis (AAV) for decades. This protocol is effective in 70-90% of patients resulting in drastic improvement in both renal and patient survival. Nevertheless, cyclophosphamide is associated with significant rates of adverse events, namely severe infections and malignancies. The authors present the single-center experience of the use of CYC for AAV treatment regarding clinical presentation, immunosuppression protocol, outcomes and adverse events, as well as a comparison with the main RCTs and studies using CYC for induction of remission of AAV. Method Retrospective analysis of clinical records of patients with AAV diagnosis (de novo or relapse) treated with CYC in the ward of the Nephrology Department of Centro Hospitalar Universitário Lisboa Norte between January 2006 and December 2019. Results Thirty patients with AAV diagnosis treated with CYC for induction of remission were identified. Average age was 69.4 ± 11.5 years. On admission, serum creatinine (SCr) was 5.03 mg/dL ± 2.24 mg/dL (eGFR 13.3 mL/min/1.73 m2 ± 11.1 mL/min/1.73 m2). Twenty patients (67%) required renal replacement therapy at admission and 12 (40%) had alveolar hemorrhage. The average Birmingham Vasculitis Activity Score (BVAS) was 27.5 ± 11.5. Immunosuppressive regimens varied considerably, as they were left to the clinician's consideration. Intravenous methylprednisolone pulses were performed in 29 (96.7%) patients, with total dose ranging from 1000 mg to 5000 mg. Cyclophosphamide was also prescribed at clinician’s choice, with only one patient receiving oral CYC and 29 patients receiving from 1 to 11 pulses in different doses. Plasma exchange was performed in 12 (40%) patients due to alveolar hemorrhage and/or rapidly progressive renal insufficiency. After induction of remission, twenty patients received maintenance therapy. On a 12-month follow-up, 9 (30%) patients were on renal replacement therapy and, in the remaining patients, mean SCr was 2.23 ± 0.98 mg/dL (eGFR 33.4 mL/min/1.73 m2 ± 19.8 mL/min/1.73m2). Fifteen (50%) patients experienced severe infection at 6 months, 3 (10.7%) patients developed malignancies and 7 (23.3%) patients died on a 12-month follow-up. Conclusion Our cohort of patients treated with CYC is unlike the population that underwent clinical trials. In our cohort, SCr at presentation was considerably higher, being only comparable to MEPEX and the control arm of RITUXVAS. The BVAS score of our patients was also significantly superior than all other studies. Furthermore, most clinical trials do not include patients with alveolar hemorrhage, present in 40% of the patients in our study, nor RRT requirement, present in 67% of our patients. The higher rate of severe infections and mortality registered in our cohort reflects the severity of the disease at presentation, but also highlights the importance of modifying immunosuppression to the population and the need for future regimens which can reduce the rate of adverse effects.

P0458ADVERSE EVENTS AND INFECTIONS, POTENTIALLY RELATED TO GLUCOCORTICOIDS, REMAIN COMMON DURING MAINTENANCE TREATMENT OF ANCA ASSOCIATED VASCULITIS AND ADD TO CLINICAL AND HEALTHCARE RESOURCE USE BURDEN IN EUROPEAN PATIENTS

Abstract Background and Aims ANCA associated vasculitis (AAV) treatment aims to quickly control vasculitis activity and then prevent relapse during the maintenance phase of this long term condition. Patients are at risk from disease and treatment related complications with high dose and/or long term glucocorticoid use being a major concern. This retrospective study examined adverse events, infections and healthcare resource use in patients managed in routine practice. Method 1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (61% Nephrologists) who completed induction therapy for new or relapsing organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months. 51% had microscopic polyangiitis, mean age 54.2 years with 56% male. BVAS was not used routinely but 56% had moderate systemic disease and 44% severe systemic disease at the time of start of induction remission treatment. Results 78% patients had comorbidity (48% hypertension, 20% dylipidaemia, 17% type 2 diabetes mellitus, 14% depression, 13% COPD/asthma and 9% had BMI &amp;gt; 35) at induction treatment start. Maintenance was defined by physicians as starting approximately 6 months into treatment. AEs potentially linked to GCs were common (values are %, bp = hypertension, DM = diabetes mellitus) during the maintenance phase and many patients remained on long term glucocortioids. Infections were also common, in particular upper (URTI) and lower respiratory tract (LRTI) infection and urinary tract infections (UTI). Hospitilisations still occurred during maintenance period, in particular these are due to infections. Maintenance treatment varied and was changed over follow up (in 13-19% patients at each time point) and in a proportion of patients the change in treatment was precipitated by an adverse event or infection (6 months 21%, 12 months 22%, 18 months 23%, 38 months 26%). Conclusion Comorbidity is common in AAV patients and needs to be considered carefully when making treatment decisions. Patients receiving maintenance therapy frequently experience potentially GC related AEs and infections are also common. Healthcare resource use continues in the maintenance phase and this is on the background of comorbidity, less then complete remission rates and high use of long term steroids. New approaches are required to reduce clinical and healthcare system burdens during the maintenance treatment phase of AAV.

Multicentric study comparing cyclosporine, mycophenolate mofetil and azathioprine in the maintenance therapy of lupus nephritis: 8years follow up.

The ideal long-term maintenance therapy of Lupus Nephritis (LN) is still a matter of debate. The present study was aimed at comparing the efficacy/safety profile of cyclosporine (CsA), mycophenolate mofetil (MMF) and azathioprine (AZA) in long-term maintenance therapy of LN. We performed a retrospective study of patients with biopsy-proven active LN. After induction therapy, all patients received maintenance therapy with CsA, MMF or AZA based on medical decision. Primary endpoint was complete renal remission (CRR) after 8years (defined as proteinuria < 0.5g/24h, eGFR > 60ml/min/1.73mq); secondary endpoints were: CRR after 1year, renal and extrarenal flares, progression of chronic kidney disease (CKD stage 3 or above) and side-effects. Out of 106 patients, 34 received CsA, 36 MMF and 36 AZA. Clinical and histological characteristics at start of induction therapy were comparable among groups. At start of maintenance therapy, CsA patients had significantly higher proteinuria (P = 0.004) or nephrotic syndrome (P = 0.024) and significantly lower CRR (23.5% vs 55.5% on MMF and 41.7% on AZA, P = 0.024). At one year, CRR was similar in the three groups (79.4% on CsA, 63.8% on MMF, 58.3% on AZA, P = 0.2). At 8years, the primary endpoint was achieved by 79.4% of CsA vs 83.3% of MMF and 77.8% of AZA patients (P = 0.83); 24h proteinuria, serum creatinine, eGFR were similar. CKD stage 3 or above developed in 8.8% of CsA, in 8.3% of MMF and in 8.3% of AZA patients (P = 0.92). Flares-free survival curves and incidence of side-effects were not different. This is the first study comparing CsA, MMF and AZA on long-term LN maintenance therapy. All treatments had similar efficacy in achieving and maintaining CRR, despite more severe baseline clinical features in patients treated with CsA.

Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM).

e20557 Background: The ideal choice of maintenance therapy in patients with HRMM high-risk multiple myeloma remains unknown. We analyzed the outcomes of patients with HRMM undergoing transplant receiving different maintenance approaches. Methods: Patients with MM undergoing their first ASCT from 2012-19 within 1 year of diagnosis were identified from the prospectively maintained database of patients undergoing ASCT. HRMM was defined as having t(4;14), t(14;16), t(14;20), del17p13, or gain 1q detected on fluorescent in situ hybridization (FISH). Results: Of the 412 patients undergoing ASCT within 1 year of diagnosis, 333 had FISH data available and of these, 37% (124/333) patients had high-risk cytogenetics. Distribution of HR cytogenetics was as follows: deletion 17p: 37% (n = 46), t(4;14): 27% (n = 34), t(14;16) or t(14;20): 12% (n = 26), gain1q: 31% (n = 41). 9% (n = 12) had more than one HR abnormality. In patients with HRMM, median age at transplant was 59 years (range: 39 to 73), and 61% (n = 103) were males. 64% (n = 107) of high-risk patients received post-transplant maintenance therapy. Maintenance therapy in this group included a proteasome inhibitor (PI) in 34% (n = 29), immunomodulatory drug (IMiD) in 59% (n = 51), or both in 7% (n = 6). There was no difference in baseline characteristics of HRMM patients receiving PI vs. IMiD maintenance, except that patients with del17p were more likely to receive PI maintenance therapy (55% vs 28%, p = 0.01). (Table) After a median follow-up of 3.1 years from diagnosis, patients with HRMM had inferior PFS compared to patients with standard risk disease, with median PFS of 3 vs. 4.8 years, p &lt; 0.001. Amongst the 86 HRMM patients receiving maintenance therapy, median PFS in patients receiving PI vs. IMiD vs. both PI + IMiD maintenance was 3 vs. 3.2 vs. 2.2 years, respectively, log-rank p = 0.7. In the sub-group of patients with 17p deletion, median PFS in the three groups was 3 vs. 2.9 vs. 2.2 years, respectively, log-rank p = 0.7. Conclusions: Patients with HRMM have inferior PFS compared to patients with standard risk disease. We observed similar outcomes in HRMM patients post-transplant regardless of the choice of maintenance therapy. [Table: see text]

Concordance of provider treatment patterns with NCCN oncology treatment guidelines (NCCN Guidelines) for metastatic non-small cell lung cancer (mNSCLC).

e21574 Background: mNSCLC clinical treatment guidelines are rapidly evolving, however, their influence on prescriber use of anti-cancer treatment regimens is not known. This retrospective study evaluated whether US patients with mNSCLC received first line (1LOT), second (2LOT), or third (3LOT) line treatment regimens that were concordant with NCCN Category 1-2A recommendations. Methods: mNSCLC patients who initiated treatment between 2014-2017 were identified using medical and pharmacy claims from the 100% Medicare Fee-for-Service (FFS) Part A/B/D sample and multi-payer Inovalon MORE2 Registry. Claims-based algorithms identified mNSCLC and LOT following diagnosis; patients with other primary cancers or &lt; 6 months follow-up were excluded. Treatment regimens were compared to active NCCN Guidelines at time of treatment to determine if regimen was concordant with Category 1-2A recommendations. Genetic mutation/biomarker status was not available. Results: 6,523 patients with mNSCLC met criteria for analysis (FFS/Medicare Advantage:78.6%; commercial:14.0%, managed Medicaid:7.4%; mean age:69.3 [SD:9.2]). For 1LOT, 81% received platinum-based doublet regimens; most common monotherapy included erlotinib, nivolumab, and pembrolizumab; 18% of 1LOT patients received maintenance therapy. For 2LOT, approximately one-third received nivolumab monotherapy, one-third received platinum-based doublets, and remainder received other regimens. Most common 3LOT included monotherapy nivolumab, pemetrexed, paclitaxel, and docetaxel. NCCN Guidelines concordance varied: 1LOT (90.5%), 2LOT (58.5%), 3LOT (71.9%). Non-concordant regimens included nivolumab as 1LOT and early adoption of platinum agent+(pemetrexed or paclitaxel) in 2LOT, and chemotherapy as 2LOT in anaplastic lymphoma kinase rearrangement-positive or epidermal growth factor receptor mutation-positive disease. Conclusions: In Medicare and non-Medicare patients with mNSCLC, 1LOT closely followed NCCN Guidelines. Most variability was observed in 2LOT where 58.5% regimens were concordant with Category 1-2A recommendations. Non-concordance may be driven by lack of effective second-line regimens and early adoption of innovative therapies.