Discontinuation Of Maintenance Therapy Research Articles

Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP).

106 Background: Measurable residual disease (MRD) negativity is a potential marker for the absence of disease in multiple myeloma (MM), which could be used to guide treatment cessation. MRD2STOP (NCT04108624) is a prospective study investigating outcomes among patients with sustained multimodal MRD negativity who discontinue maintenance therapy. Methods: Discontinuation of maintenance was permitted if MRD negative by PET/CT, flow cytometry (limit of detection [LoD] 10-5), and NGS by clonoSEQ (threshold 10-6). Patients underwent serial blood testing along with clonoSEQ, flow, and PET/CT annually for 3 years. Concurrent BM aspirate samples also underwent CD138+ immunomagnetic enrichment analyzed using clonoSEQ to achieve MRD 10-7 sensitivity. Primary endpoints were MRD resurgence rate at the 10-6threshold, along with progression-free survival (PFS) and overall survival among those MRD negative by the standard non-enriched clonoSEQ. Results: 83 patients were screened, and 47 patients met eligibility to discontinue maintenance as of 1/21/24. Median age was 66 years (range 39-84). 17 (36%) had high-risk disease at diagnosis (8 with 1q copy abnormalities, 5 with ISS stage 3, 2 with t(4;14), 1 with t(14;16), and 3 with del17p). Most (45/47, 96%) had one line of therapy; 26 (55%) received a triplet and 19 (40%) a quadruplet. Prior autologous transplant was received by 30 (64%) and multi-drug consolidation in 36 (77%) prior to single-agent maintenance. 96% received lenalidomide as maintenance. Median duration of consolidation/maintenance therapy prior to discontinuation was 36 months (range 12-95), including 14 (30%) with <27 months. Median follow-up was 30 months. Of 47 enrolled patients, 5 (11%) experienced disease progression and an additional 6 (13%) had MRD resurgence at 10-6. Of 11 MRD resurgent events, 4 (36%) were MRD 10-7 positive at baseline, and 3 (27%) were MRD 10-7 positive 1 year prior to MRD 10-6 resurgence. 2 second hematologic cancers occurred during follow-up: 1 Hodgkin lymphoma and 1 B-ALL, the latter which resulted in the only patient death on study. The estimated 3-year PFS was 85%, including 93% for patients MRD 10-7 negative (n=40) at baseline and 31% for those MRD 10-7 positive (n=7) at baseline (logrank p<0.001). Among the MRD evaluable patients (n=45), the 3-year MRD-free survival (MRD-FS) was 68%; 78% for patients MRD 10-7 negative (n=38) and 33% for patients MRD 10-7 positive (n=7) (logrank p<0.001). There were no differences in MRD-FS or PFS when stratified by high-risk disease, receipt of transplant, consolidation, or duration of maintenance. Conclusions: Discontinuation of maintenance therapy among patients with MM and multimodal MRD-negativity results in a high rate of sustained MRD-negativity and lack of disease progression. CD138+-enriched MRD samples using the clonoSEQ assay may help to even better identify patients who can discontinue therapy. Clinical trial information: NCT04108624 .

Relapse and side effects of steroid therapy beyond 3 years in autoimmune pancreatitis: A multicenter retrospective study

BackgroundThe impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. MethodsIn this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. ResultsOf 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07–13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04–7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). ConclusionsCessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.

Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma

AbstractFrom November 2014 to May 2017, 332 patients homogeneously treated with bortezomib, lenalidomide, and dexamethasone (VRD) induction, autologous stem cell transplant, and VRD consolidation were randomly assigned to receive maintenance therapy with lenalidomide and dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients). RD consisted of lenalidomide 15 mg/d from days 1 to 21 plus dexamethasone 20 mg/d on days 1 to 4 and 9 to 12 at 4-week intervals, whereas in the IRD arm, oral ixazomib at a dose of 4 mg on days 1, 8, and 15 was added. Therapy for patients with negative measurable residual disease (MRD) after 24 cycles was discontinued, whereas those who tested positive for MRD remained on maintenance with RD for 36 more cycles. After a median follow-up of 69 months from the initiation of maintenance, the progression-free survival (PFS) was similar in both arms, with a 6-year PFS rate of 61.3% and 55.6% for RD and IRD, respectively (hazard ratio, 1.136; 95% confidence interval, 0.809-1.603). After 2 years of maintenance, treatment was discontinued in 163 patients with negative MRD, whereas 63 patients with positive MRD continued with RD therapy. Maintenance discontinuation in patients tested negative for MRD resulted in a low progression rate (17.2% at 4 years), even in patients with high-risk features. In summary, our results show the efficacy of RD maintenance and support the safety of maintenance therapy discontinuation in patients with negative MRD at 2 years. This trial was registered at www.clinicaltrials.gov as #NCT02406144 and at EudraCT as 2014-00055410.

Examination on Factors Affecting Symptom Change after Drug Withdrawal in Patients with Mild Erosive Gastroesophageal Reflux Disease Undergoing Symptom-Controlled Maintenance Therapy with Acid-Secretion Inhibition Drugs

Introduction: In patients with gastroesophageal reflux disease (GERD) on maintenance therapy with acid-suppressive drugs, it is not clear what background factors allow patients to discontinue the drugs. The aims of this study were to examine the relationship of the changes in the frequency and severity of gastrointestinal symptoms after discontinuation of acid-secretion inhibitors for erosive GERD (eGERD) with possible patient background factors and to identify factors that influence these changes. Methods: This is a multicenter, open-label, interventional, exploratory study. eGERD patients with mild mucosal injury whose symptoms were under control and who were on maintenance therapy with acid-suppressive drugs were withdrawn from the drug treatment for 4 weeks. We examined the relationship of patient backgrounds (sex, age, body mass index, alcohol consumption, smoking habits), esophageal hiatal hernia, Helicobacter pylori infection, pepsinogen I and II concentrations and I/II ratios, blood gastrin levels before and after drug discontinuation with total score change in Frequency Scale for the Symptoms of GERD (FSSG). Results: Of the 92 patients whose symptoms could be assessed before and after drug withdrawal, 66 patients (71.7% of the total) had FSSG <8 and no symptom relapse after the withdrawal. Furthermore, patient background factors that may be related to symptom relapse/non-relapse were examined, but no related factors were detected. The maintenance medications before discontinuation in the above 92 patients were a proton pump inhibitor (PPI) and vonoprazan (VPZ, a potassium ion competitive acid blocker). Since PPI and VPZ were administered to about the same number of patients, though incidentally, we additionally examined the relationship between patient background factors and symptom relapse/non-relapse by treatment group. As a result, no relevant background factors were detected in both groups. Although there were no significant differences between the two groups, the severity and frequency of symptom recurrence in the VPZ group tended to be higher than in the PPI group. Conclusions: Consideration of background factors is unlikely to be required in the discontinuation of maintenance therapy for eGERD. There was no significant difference in the extent of disease or frequency of recurrence during the discontinuation period, regardless of whether the drug before discontinuation was a PPI or VPZ.

Maintenance therapy with monoclonal antibodies in metastatic HER2-positive breast cancer: A review of studies

Maintenance therapy is a medical treatment after achieving stabilization, partial or complete response by the first line therapy of a metastatic malignant tumor. The goals of such treatment are to maintain the effect of the first line therapy, to increase progression-free survival, and, in some cases, overall survival. Targeted monoclonal antibody therapy is a maintenance treatment option widely used in clinical practice for metastatic HER2-positive breast cancer, but it remains one of the least studied. This analysis of available world studies was carried out in order to form an idea about the possibilities of maintenance therapy and promising areas for studying this topic. The article presents an up-to-date and complete review of data on metastatic HER2-positive breast cancer maintenance therapy with various drugs from the monoclonal antibody group, as well as cases of discontinuation of maintenance therapy due to high toxicity or at the request of the patient. Besides, authors analyzed the treatment options of maintenance therapy in patients with luminal HER2-positive breast cancer and the possibilities of intensifying monoclonal antibody maintenance therapy by antihormonal drugs for this group of patients.

The Landscape of Maintenance Therapy Trials Following Autologous Transplant for Multiple Myeloma

BACKGROUND: The current standard for maintenance therapy following autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) is lenalidomide, an oral treatment with demonstrated overall survival benefit. Other options for MM may incur toxicities or require frequent visits to infusion centers and may thus not be best suited as maintenance. Patients with high-risk cytogenetic features have poorer outcomes than those considered to have standard risk disease, and national guidelines recommend doublet maintenance (with a proteasome inhibitor and lenalidomide in this setting). Currently, the role of minimal residual disease (MRD) in treatment decision making is unknown but MRD status in this setting may dictate treatment discontinuation in the future. We conducted a review of currently enrolling clinical trials to characterize therapeutic agents/strategies being used or evaluated in a maintenance setting, outcomes evaluated, the inclusion of high-risk patients, and the use of MRD response in guiding management decisions. METHODS: A comprehensive search was performed on the clinicaltrials.gov, clinicaltrialsregister.eu, and anzctr.org.au databases on March 2, 2022, using the keywords "newly diagnosed multiple myeloma", "transplant eligible multiple myeloma", and "maintenance in multiple myeloma". Only studies that were currently recruiting patients, or those listed as active but not yet recruiting were included. Studies that completed enrollment, were terminated, or had been presented or published were not included. Studies were included if patients were planned to undergo autologous stem cell transplant after induction therapy followed by maintenance strategy. If at least one arm received post-transplant maintenance therapy, and the maintenance therapy was specified in the trial description, it was included. Trials evaluating maintenance therapy after a salvage transplant or maintenance therapy in non-transplant settings were excluded. RESULTS: A total of 20 studies were analyzed. Table 1 highlights characteristics. Of the 20 studies, 11 (55.0%) were randomized and 9 (45.0%) were non-randomized. Six studies (30.0%) evaluated PFS as a primary outcome, and 2 studies (10.0%) included OS as a primary outcome. Four of the 20 (20.0%) studies included multiple primary endpoints in addition to time to event outcome, while 4 (20.0%) had a time to event outcome as the sole primary outcome being investigated. Of the 11 randomized studies, 2 studies evaluated OS (18.1%) and 5 evaluated PFS (45.5%) as primary endpoint. MRD negativity was included as a primary endpoint in 11 studies (55.0%) and a secondary endpoint in seven (35%). Of the 9 nonrandomized studies, 4 had a primary endpoint of MRD negativity rate (44.4%), 2 (22.2%) had response-based primary outcomes, and one (11.1%) had a time to event primary outcome. Of the total trials, two (10.0%) assessed or mandated discontinuation of maintenance therapy for those achieving MRD negativity. Table 2 describes maintenance regimens utilized. A total of 4 randomized studies assessed comparison of lenalidomide and another agent to lenalidomide alone with a primary endpoint powered for PFS/OS. Only one study limited enrollment to standard risk disease. No studies enrolled only "high-risk" disease. Amongst a total of 19 trials enrolling patients with high-risk disease, eight trials (42.1%) were offering or permitting patients with high-risk disease to receive single agent lenalidomide. CONCLUSION: Our study analyzing the landscape of current maintenance trials demonstrates that there are many promising clinical trial designs that adapt treatment based on the depth of responses and incorporate newer agents with enough statistical power to demonstrate OS advantage. However, there remains room for improvement, as evidenced by trials evaluating drugs with marked toxicity profiles in non-randomized single arm settings, patients with high-risk disease being permitted to receive treatment that may be inferior to what current guidelines recommend, and a lack of patient centered endpoints (such as OS or quality of life) being evaluated as primary endpoints. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prospective Trial Using Multimodal Measurable Residual Disease Negativity to Guide Discontinuation of Maintenance Therapy in Multiple Myeloma (MRD2STOP)

Prospective Trial Using Multimodal Measurable Residual Disease Negativity to Guide Discontinuation of Maintenance Therapy in Multiple Myeloma (MRD2STOP)

Early versus Late Discontinuation of Maintenance Therapy in Multiple Myeloma.

Maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM) is the standard treatment and recommended to be continued until disease progression. However, in the real world, patients discontinue treatment due to various reasons. We sought to determine the effect of early versus late discontinuation on survival outcomes in MM patients who underwent ASCT at The Ohio State University. We retrospectively reviewed 340 patients who underwent ASCT from 2005 to 2016 and received maintenance therapy for at least six months without progression. We compared the outcomes of patients who received maintenance for three years or less (early group) to the patients who continued maintenance beyond three years (late group). Lenalidomide (89%) and bortezomib (10%) were the most common agents used for maintenance chemotherapy. In Kaplan–Meier analysis, patients in the late group had prolonged progression-free (PFS) (p < 0.001) and overall survival (OS) (p < 0.001). The 5-year estimated OS in late group was 96% vs. 79% in the early group and 5-year PFS was 80% in late group vs. 50% in the early group. The most common reasons for discontinuation of maintenance in early group were adverse events (55.9%) and patient preference (22.5%). For the late group, it was disease progression (23.9%) and adverse events (14.3%). Fifty-five percent of patients in the late group were still on maintenance treatment at the last follow-up. Continuation of maintenance therapy was thus associated with improved outcomes, while adverse events prevented most patients from continuing treatment.

PB2033: INFLUENCE OF INDUCTION THERAPY WITH LENALIDOMIDE ON MAINTENANCE THERAPY AND PROGNOSIS AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA

Background: We have finished a single-center, prospective study registered at www.chictr.org.cn (ChiCTR1900021558). 60 newly diagnosed multiple myeloma (NDMM) patients were included from 2017 to 2018, which were divided into lenalidomide, liposomal doxorubicin, and dexamethasone (RAD) group (n=30) or bortezomib, liposomal doxorubicin, and dexamethasone (PAD) group (n=30). Patients received 4-6 cycles of RAD or PAD induction therapy every 4 weeks, with subsequent autologous stem cell transplantation (ASCT) and maintenance therapy. This prospective study showed that the failure rate of stem cell mobilization in the RAD group was significantly higher than that in the PAD group. The hematopoietic reconstruction time in the RAD group was longer than that in the PAD group. Aims: Comparison of the process of maintenance therapy, efficacy, and prognosis between RAD induction and PAD induction in patients in previous clinical studies. Methods: Patients who completed induction therapy, ASCT, and received maintenance therapy through the previous clinical trial in our center were retrospectively analyzed. We divided enrolled patients into two groups according to the induction regimens, and compared maintenance treatment discontinuation, efficacy, time to progress (TTP), and overall survival (OS) between the RAD group and the PAD group. Results: 21 patients in the PAD group and 12 patients in the RAD group were enrolled in the study, the median follow-up time was 44.6 months. 28 patients received thalidomide and 5 received lenalidomide at the beginning of maintenance therapy. The rate of maintenance treatment discontinuation was higher in the RAD group compared to the PAD group (41.7% vs. 4.8%, P=0.016), but the interval of maintenance treatment discontinuation was not statistically different (1.0 month vs. 0.9 months, P=0.917). During maintenance treatment, patients in the RAD group had a lower median count of white blood cells than the PAD group (2.96×109/L vs. 3.38×109/L, P=0.033), and so did the median count of platelets (102×109/L vs. 150×109/L, P=0.011). The incidence of grade 3/4 hematologic adverse events (AEs) was also higher in the RAD group than in the PAD group (66.7% vs. 28.6%, P=0.033). The ratio of patients who achieved CR and MRD-negative in the RAD group was lower than those in the PAD group (P=0.047 and 0.016, respectively). The median TTP and median OS were not reached in both groups, but the median TTP and OS in the RAD group were shorter than those in the PAD group (P=0.032 and 0.022, respectively). Reinfusion of CD34+ cells <2×106/L was an independent prognostic factor for TTP (P=0.009); minimum count of platelets <50×109/L might be an independent prognostic factor for OS (P=0.050). Summary/Conclusion: Patients who received the RAD induction had worse efficacy and prognosis after receiving maintenance therapy compared to the PAD group, possibly due to discontinuation of maintenance therapy caused by a higher incidence of grade 3/4 hematologic AEs.

The effect of discontinuation of maintenance therapy in Chinese patients with MPO-ANCA associated vasculitis who were in long-term stable remission.

There is a consensus that maintenance therapy should be used to prevent relapse of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV), but there is a debate about the optimal duration of maintenance therapy. Therefore, the purpose of this study was to determine whether discontinuation of maintenance therapy in MPO-AAV patients who were in long-term stable remission affects relapse, renal survival and patient survival. Seventy-nine patients with MPO-AAV diagnosed at Xiangya hospital from June 2010 to June 2019 who were in stable remission for at least 18months following maintenance therapy were included. Patient records were retrospectively reviewed, and based on whether patients discontinued maintenance therapy 18months after commencing maintenance therapy, patients were assigned into either the withdrawal group (n = 26) or maintenance group (n = 53). The endpoint was the percentage of relapse, relapse-free survival, renal survival and patient survival during follow-up. Ten relapses (38.5%) occurred in the withdrawal group (n = 26) and 8 relapses (15.1%) occurred in the maintenance group (n = 53) (p = 0.020). Compared to the withdrawal group, the maintenance group had similar relapse-free survival (log-rank test p = 0.099). But maintenance group had a better renal survival (p = 0.035), with no difference in patient survival or adverse events. This study suggests that discontinuing maintenance therapy at 18months following induction of sustained remission leads to a significant increase in the percentage of relapse, and decreases renal survival in patients with MPO-AAV, but does not decrease relapse-free survival or patient survival.

Early Versus Late Discontinuation of Maintenance Therapy in Multiple Myeloma

Background: Indefinite maintenance therapy after autologous stem cell transplant (ASCT) is the current standard of care in multiple myeloma (MM). However, in the real world, patients often discontinue treatment due to various reasons. In this study, we sought to analyze the effect of and reasons for early discontinuation of maintenance therapy on survival outcomes, studying patients who received less than 3 years of maintenance therapy (short-term maintenance group) or more than 3 years (continuous maintenance group).Methods: We retrospectively reviewed 340 patients who underwent ASCT from 2005-2016 and received maintenance therapy for at least six months without progression. The patients started maintenance therapy after 100 days of ASCT. Lenalidomide (89%) and bortezomib (10%) were the most commonly used agents for maintenance therapy. The primary endpoints included were progression-free survival (PFS) and overall survival (OS). All the endpoints were measured from the time of ASCT. The discontinuation was defined as permanently stopping the maintenance therapy. Patient, disease, and transplant-related characteristics were compared between the two groups using the Mann-Whitney U test for continuous variables, and chi-squared or Fisher's exact test for categorical variables. The probabilities of PFS and OS were calculated using the Kaplan-Meier (KM) method and compared using log-rank test.Results: One hundred and two (n= 102; 30%) patients discontinued maintenance therapy in the first 3 years (short-term maintenance group), while 238 patients remained on maintenance therapy for ≥ 3 years (continuous maintenance group). The groups had similar baseline characteristics in terms of age, gender, ISS staging, cytogenetics, response before ASCT, and melphalan dosing. About 20% of patients in both groups were older than 65 years. Among those alive at the last contact, the median follow up were 5.4 years and 6.1 years for the short-term and continuous maintenance therapy group, respectively. At the time of the last follow-up, 131/238 (55%) patients in the continuous maintenance group were still on maintenance therapy. The median PFS in the short-term maintenance group was 5.1 years (95% CI: 4.4-7.4) and median OS was 9.8 years (95% CI: 8.2- to NR), whereas in the continuous maintenance group both median PFS (95% CI: 8.5- NR) and OS were not reached. This latter group had significantly longer PFS and OS than the short-term maintenance group with a 5-year estimated PFS of 80% (95%CI: 74-85%) vs. 50% (95% CI: 39-60%) (p<0.001) and OS of 96% (95% CI: 92-98%) vs. 79% (95% CI: 69-86%) (p<0.001) (Figure 1). This remained significant after adjusting for race, post-transplant remission status and ISS staging, with an hazard ratio for risk of relapse or death of 0.31, 95% CI: 0.21-0.45; and HR for risk of death of 0.34, 95% CI: 0.18-0.64.The most common reasons for early discontinuation of maintenance therapy (< 3 years) were adverse events related to maintenance therapy (58%). Four patient (4%) patients developed second primary malignancy (SPM) in this group. The most frequent hematological adverse events (AEs) were pancytopenia and isolated neutropenia. Fatigue and diarrhea were the most common non-hematological AEs. The reasons for stopping maintenance in the continued maintenance group were disease progression (24%) and adverse events (14%), while five patients (2%) developed SPM.Conclusion: In our institutional experience, 30 percent of MM patients discontinued maintenance therapy within 3 years of ASCT due to AEs or patient preference. These patients had inferior PFS and OS after ASCT compared to patients on continuous maintenance. Therefore, continuation of maintenance therapy should be strongly encouraged as safely possible and strategies like dose reduction or switching therapy are recommended. [Display omitted] DisclosuresBumma: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Reasons for first-line maintenance therapy discontinuation among patients with newly diagnosed advanced ovarian cancer treated in real-world settings.

290 Background: PARP inhibitor (PARPi) and bevacizumab have been integrated into the first-line (1L) maintenance therapy for patients (pts) with ovarian cancer (OC). However, due to adverse events, the rate of PARPi maintenance discontinuation was 12% in the SOLO1 clinical trial. We aimed to better understand the rate and cause of maintenance therapy discontinuation in real-world practice. Methods: This retrospective cohort study was conducted using de-identified electronic health record (EHR)–derived data from the nationwide Flatiron Health electronic health database. From January 1, 2016, to February 29, 2020, data were obtained for pts with newly diagnosed stage III/IV epithelial OC who received primary debulking surgery followed by 6–9 cycles of 1L platinum-based chemo or neoadjuvant chemo followed by interval debulking surgery. Index date was the end of 1L systemic therapy. Results: Of 675 pts with stage III/IV OC who underwent primary systemic therapy, 144 (21.3%) received 1L maintenance therapy and were included in the analysis. Mean age was 65.0 y. Most pts were treated in community practice (93.1%), had ECOG score of 0–1 at diagnosis (81.3%), and were shown to be BRCA wild type (66.7%). Bevacizumab was the most common 1L maintenance therapy (n = 69, 47.9%), followed by olaparib (n = 46, 31.9%), paclitaxel (n = 18, 12.5%), rucaparib (n = 10, 6.9%), and gemcitabine (n = 1, 0.7%). Overall, 34 (23.6%) pts discontinued 1L maintenance therapy. The most common reason for discontinuation was disease progression (n = 19, 13.2%), followed by treatment-related toxicity (n = 13, 9.0%; Table). Of 56 pts who received PARPi (olaparib or rucaparib) 1L maintenance therapy, 21 (37.5%) pts discontinued treatment: 11 (19.6%) because of disease progression, 9 (16.0%) treatment-related toxicity, and 1 for other reasons. Conclusions: In pts with advanced OC who received 1L maintenance therapy in clinical practice, disease progression was the most common reason for maintenance therapy discontinuation. The rates of toxicity-related discontinuations were comparable with those reported in clinical trials.[Table: see text]

Lenalidomide Maintenance Therapy after Autologous Peripheral Blood Stem Cell Transplant (PBSCT) in Multiple Myeloma Patients: Factors That Impact Treatment

IntroductionMaintenance therapy after an Autologous PBSCT remains the standard of care in patients with Multiple Myeloma, having been shown to increase progression free survival, and based on the CALGB study, overall survival. Accordingly, Lenalidomide maintenance became an important part of therapy offered in the management of patients with Multiple myeloma. We set out to perform a study to assess the clinical application of Lenalidomide maintenance in the post-transplant setting. We assessed all factors cited by physicians as a reason to offer, not offer, or discontinue maintenance therapy. Patient factors were also studied in regards to reasons for starting, continuing, or discontinuing Lenalidomide maintenance therapy post-transplant.MethodsThis study was IRB approved by the Henry Ford Cancer Institute. A retrospective chart review of 128 consecutive patients who received Autologous PBSCT at our institution was conducted between the time periods of March 2010 to December 2016.ResultsIn patients that were eligible and offered Lenalidomide maintenance after Autologous PBSCT, 70% (70/99) received maintenance therapy (see Table 1). The trend to offer Lenalidomide maintenance therapy in patients post PBSCT increased from 45% to nearly 80% by 2016 (see Table 2).By June of 2015, 45 patients had started maintenance, of which 42% completed 2 years of maintenance by June of 2017. There were 14% (10/70) of patients who received maintenance therapy until progression, while 20% (14/70) continue to be on maintenance without significant side effects. Neutropenia or thrombocytopenia accounted for 20% (14/70) of patients discontinuing maintenance therapy. In our patient population there were no reports of secondary malignancies.Twenty two percent (29/128) of patients declined maintenance therapy. Of these 29 patients 65% (19/29), did not have a specified reason documented for declining therapy in their charts.In maintenance eligible patients, 22% (29/128) were not offered maintenance therapy. Of these patients, 24% (7/29) had no documented reason, another 24% were not offered maintenance due to stringent complete response (sCR), and 20% (6/29) due to progressive disease (PD).ConclusionWe set out to study real world application of Lenalidomide maintenance post autologous PBSCT based on both patient and physician factors. Physician preference for not offering maintenance therapy appeared to be based on achievement of sCR or in the setting of PD. This preference was mainly documented until 2013. After 2013, the trend to offer Lenalidomide maintenance therapy in patients increased from 45% to nearly 80% by 2016, suggesting increasing influence of emerging data on Lenalidomide maintenance therapy post autologous PBSCT. We also noted that neutropenia and thrombocytopenia were important factors for discontinuation of maintenance therapy, similar to the 20% incidence of most commonly reported grade 3 and 4 adverse events with IFM 2005-02 and CALGB 100104 study. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognosis and Long-Term Outcome of Women With Idiopathic Recurrent Vulvovaginal Candidiasis Caused by Candida albicans.

This study evaluated use of long-term fluconazole beyond an initial 6-month course of weekly fluconazole in premenopausal patients with idiopathic recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans. A retrospective chart review was performed of women seen in Wayne State University Vaginitis Clinic with culture-confirmed idiopathic RVVC due to Candida albicans during a 10-year period (January 2006 to December 2015). Only patients without risk factors for secondary VVC and who initiated a 6-month course of weekly fluconazole therapy were selected. Data included long-term use of fluconazole therapy, treatment efficacy, and development of fluconazole resistance. Questionnaires were mailed to evaluate patient's experience after fluconazole therapy. Of 883 patients with RVVC based on clinical records, 191 with culture positive idiopathic RVVC due to C. albicans were started on the maintenance fluconazole regimen, and 147 (77.0%) completed 6 months of therapy. Of these, 107 (72.8%) continued or received maintenance past 6 months. The most common reason for additional fluconazole therapy was culture-confirmed VVC recurrence (55.1%), unconfirmed but possible VVC recurrence (16.8%), and patient preference (10.3%). The mean duration of fluconazole maintenance was 35.7 (range = 7-288) months. Fluconazole resistance emerged in 7.5% completing 6-month therapy. Upon questionnaire follow-up, 93.6% of 51 respondents reported benefit during maintenance regimen; however, 80.9% described relapse after discontinuing weekly therapy. Fluconazole suppression therapy was highly effective in preventing VVC symptoms but was rarely curative and VVC relapse occurred frequently after discontinuation of maintenance therapy. The development of drug resistance in C. albicans isolates after long-term fluconazole maintenance therapy although uncommon is a previously unrecognized complication.

Prognosis and long term outcome of women with idiopathic recurrent vulvovaginal candidiasis caused by Candida albicans

Objectives This study evaluated use of long-term fluconazole beyond an initial 6-month course of weekly fluconazole in premenopausal patients with idiopathic recurrent vulvovaginal candidiasis (RVVC) due to Candida albicans. Materials and methods A retrospective chart review was performed of women seen in Wayne State University Vaginitis Clinic with culture-confirmed idiopathic RVVC due to Candida albicans during a 10-year period (January 2006 to December 2015). Only patients without risk factors for secondary VVC and who initiated a 6-month course of weekly fluconazole therapy were selected. Data included long-term use of fluconazole therapy, treatment efficacy, and development of fluconazole resistance. Questionnaires were mailed to evaluate patient's experience after fluconazole therapy. Results Of 883 patients with RVVC based on clinical records, 191 with culture positive idiopathic RVVC due to C. albicans were started on the maintenance fluconazole regimen, and 147 (77.0%) completed 6 months of therapy. Of these, 107 (72.8%) continued or received maintenance past 6 months. The most common reason for additional fluconazole therapy was culture-confirmed VVC recurrence (55.1%), unconfirmed but possible VVC recurrence (16.8%), and patient preference (10.3%). The mean duration of fluconazole maintenance was 35.7 (range = 7-288) months. Fluconazole resistance emerged in 7.5% completing 6-month therapy. Upon questionnaire follow-up, 93.6% of 51 respondents reported benefit during maintenance regimen; however, 80.9% described relapse after discontinuing weekly therapy. Conclusions Fluconazole suppression therapy was highly effective in preventing VVC symptoms but was rarely curative and VVC relapse occurred frequently after discontinuation of maintenance therapy. The development of drug resistance in C. albicans isolates after long-term fluconazole maintenance therapy although uncommon is a previously unrecognized complication.

Maintenance Therapy after Second Autologous Stem Cell Transplant in Multiple Myeloma Improves Overall Survival

Introduction: Low dose lenalidomide as a maintenance therapy after the first autologous transplant (autoSCT) has been shown to improve progression free survival (PFS) and possibly overall survival (OS) in standard-risk multiple myeloma (MM). Proteasome inhibitor-based maintenance therapy provides an alternative to lenalidomide and offers PFS and OS advantage in high-risk MM. Most recently oral ixazomib as a maintenance therapy has been shown to reduce the risk of progression by 28%. Despite the advances in maintenance therapy after first autoSCT, no prospective or retrospective studies exist evaluating efficacy of maintenance therapy after second autoSCT. In this retrospective study, we evaluated the impact of maintenance therapy after second autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult MM patients (pts) who received maintenance therapy following second autoSCT. Lenalidomide dose up to 15mg daily and subcutaneous bortezomib 1.3mg/m2 every 2 weeks were considered maintenance therapy. The pts who received higher doses or combinational therapy as maintenance were excluded. We compared outcomes between pts who did and did not receive maintenance therapy following second autoSCT. The objectives were to determine OS, relapse-free survival (RFS), relapse rate and non-relapse mortality (NRM) with maintenance therapy following second autoSCT using Cox regression and competing risk models. Results: Between January 2000 and December 2018, 117 pts underwent second autoSCT and met the inclusion criteria. Of these, 39 received maintenance therapy and 78 did not. Median time between first and second autoSCT was 57 months (range, 4.9-124.2) in the maintenance group and 46 months (range, 3.7-193.5) in the no-maintenance group (p=0.32). Disease status at second autoSCT was complete response (CR) (n=7, 6%), very good partial response (VGPR) (n=22, 19%), partial response (PR) (n=30, 26%), stable (n=21, 18%) and progressive disease (n=32, 27%). Melphalan-based preparative regimen was used in 87% of pts, and BEAM was used in 13% of pts. All pts successfully engrafted and median time to neutrophil and platelet engraftment was 11 and 19 days, respectively. Maintenance therapy after second autoSCT was started at a median day of 105 (range, 62-317). Lenalidomide-based maintenance therapy was commonly used in 23 (59%) pts, and bortezomib as maintenance was used in 16 (41%) pts. Sixteen pts received maintenance therapy after both first and second autoSCT, and 23 received second maintenance only. Median duration of second maintenance therapy was 16 months (range, 8.7-26.5). The best response during maintenance was CR (n=8, 21%), VGPR (n=20, 51%), PR (n=9, 23%), and stable disease (n=2, 5%). Median follow-up for OS was 48 and 60 months in the maintenance and no-maintenance group, respectively. Median OS was not reached in the maintenance group and was 40.8 months in the no-maintenance group (HR 2.32, p=0.02). At 3-year, maintenance group had superior RFS (18% vs 12%; HR 1.65, p=0.03), lower relapse rate (69 vs 81%; SHR 0.58, p=0.02). Median time to progression was 24 months in the maintenance group and 14 months in the no-maintenance group (p=0.04). Although limited by small numbers, we did not observe any impact of cytogenetics at diagnosis on OS and RFS after second autoSCT. RFS was superior with lenalidomide-based maintenance compared to bortezomib-based maintenance (HR 2.17, p=0.05). However, OS was not different. The multivariable analysis revealed that maintenance after second autoSCT was associated with significantly superior OS (HR 0.38, p=0.01), RFS (HR 0.59, p=0.03) and lower relapse rate (SHR 0.63, p=0.04). The common reasons for maintenance therapy discontinuation were disease progression (n=20, 51%), side effects (n=7, 18%), and unknown (n=12, 31%). A total of 10/39 pts who received maintenance therapy and 44/77 pts who did not receive maintenance have died. Conclusion: This is the first study showing efficacy of maintenance therapy after second autoSCT. Maintenance therapy after second autoSCT significantly improved overall and relapsed-free survival and should be considered in all pts after second transplant. Our study also reveals real world practice pattern of using variable dose of maintenance therapy among physicians. Disclosures Deol: Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board.

Discontinuation of maintenance therapy in frequently relapsing nephrotic syndrome .

Childhood steroid-dependent (SDNS) and frequently relapsing (FRNS) nephrotic syndromes often require long-term immunosuppressive therapy to maintain remission. Successful discontinuation of maintenance therapy remains to be a challenge with these children. In the following article, we report our experience on patients after discontinuation of steroid-sparing immunosuppressive maintenance therapy (IT). Thereby, we retrospectively reviewed all patients between 2006 and 2016 with a relapsing course of steroid-sensitive nephrotic syndrome (SDNS or FRNS) treated with steroid-sparing maintenance immunosuppressive medication. Patient data of a total of 24 patients were recorded for a median time of 53.5 (11.2-112) months. In 11 patients, therapy was discontinued at physician's discretion. Thereafter, 8 of 11 patients (group A) relapsed after a median time of 2.21 (0.23-9.17) months, and IT was restarted. The remaining 3 patients (group B) maintained in long-term remission for a median time of 26.9 (17.7-32.1) months until the end of observation. Neither age, at initial episode nor at discontinuation or duration of IT, differed significantly between the groups of patients with relapse after discontinuation of IT, compared to those without. There was a trend towards a shorter relapse-free interval before discontinuation in group A than in group B (35.7 vs. 44.1 months). All patients who restarted IT again attained a stable remission until the last follow-up and did not show any further relapse. These results demonstrate that a failed discontinuation attempt does not put the patient's future remission at risk. .

408. Inflammatory myositis in pregnancy. The value of early diagnosis and aggressive treatment: A case series

Introduction Inflammatory myositis’ (IM) encompasses multi-systemic autoimmune conditions including dermatomyositis (DM), polymyositis (PM) and myositis-overlaps. Diagnostic delays reflect the rarity of IM (1–6 per 1,000,000), the varying presentations associated and a dismissal of symptoms as ‘normal for pregnancy’. Immunosuppression is often withheld unduly. Objectives We aim to increase the awareness of this aggressive yet treatable condition. Methods We describe 4 cases of IM treated in pregnancy. 31 yr multigravida: Known autoimmune disease (hypothyroidism and type-1-diabetes) presents with varying symptoms throughout pregnancy: fatigue and proximal myopathy (12/40), shawl rash (22/40), pneumonia requiring intubation (25/40) and pre-eclampsia (PET) necessitating caesarean section (CS) (26/40). Post-partum, ECMO was required for a progressive organising pneumonia. The unifying diagnosis was DM, treated with IV methylprednisolone (IVMP), rituximab and cyclosporine. 35 yr multigravida: Complicated by gestational diabetes, unexplained transaminitis and proteinuria presented 38/40 with an intrauterine death. Post-partum a photosensitive rash (2/52), inflammatory arthritis (4/52) and organising pneumonia (11/52) developed. CK was normal. MDA-5 (amyopathic) DM was diagnosed and treated with IVMP, cyclophosphamide and methotrexate. 39 yr primip: Known RNA-polymerase diffuse systemic sclerosis (SSc) presented with dyspnoea and orthopnoea, requiring intubation (7/40). CK, troponin and BNP were elevated and myositis-overlap SSc with cardiac, proximal muscle and gastrointestinal involvement diagnosed. Treatment included IVMP and intravenous immunoglobulin. Steroid-sparing agents (azathioprine and rituximab) were instituted to avoid a renal-crisis. She remains pregnant. 30 yr primip: Known anti-SRP (necrotising) myositis, presented with proximal myopathy, respiratory muscle weakness and CK rise (12/40) following discontinuation of maintenance therapy. Re-treated with IVMP and rituximab at 16/40. Emergency CS (32 + 4/40) was performed for placenta praevia. Results Despite extreme presentations of IM peri-partum, all 4 patients were treated aggressively with complete resolution of symptoms. Obstetric outcomes were less favourable. Discussion Rituximab is effective and safe in early pregnancy. Pregnancy should not be a barrier to early diagnosis or treatment.

Factors associated with methadone maintenance therapy discontinuation among people who inject drugs

BackgroundMethadone maintenance therapy (MMT) continues to be a key treatment for opioid use disorder, although premature discontinuation of MMT can increase risk for overdose and other severe harms. We examined sociodemographic characteristics, substance use patterns and social-structural exposures associated with MMT discontinuation among a cohort of people who use drugs (PWUD) in Vancouver, Canada. MethodsData were derived from VIDUS and ACCESS, prospective cohorts of PWUD in Vancouver, Canada. The outcome of interest was self-reported discontinuation of MMT within the last six months. Multivariable Generalized Estimating Equations (GEE) were conducted to identify factors independently associated with MMT discontinuation. ResultsBetween 2005 and 2015, 1301 PWUD who had accessed MMT were recruited, among whom 288 (22.1%) discontinued MMT at least once during the study period. In multivariable GEE analyses, homelessness (Adjusted Odds Ratio [AOR] = 1.46, 95% Confidence Interval [95% CI]: 1.09–1.95), daily heroin injection (AOR = 5.17, 95% CI: 3.82–6.99), daily prescription opioid use (injection or non-injection) (AOR = 2.18, 95% CI: 1.30–3.67), recent incarceration (AOR = 1.46, 95% CI: 1.01–2.12), and not being on any form of income assistance (AOR = 2.14, 95% CI: 1.33–3.46) were each independently positively associated with MMT discontinuation. Participants with more study visits on methadone (>50% vs. ≤50% of visits) (AOR = 0.63, 95% CI: 0.47–0.85) and those with higher methadone dose (>100 mg vs. <60 mg per day) (AOR = 0.44, 95% CI: 0.31–0.62) were less likely to discontinue MMT. Discussion and conclusionsDiscontinuation of MMT in this urban setting was associated with recent homelessness and incarceration, not accessing social income assistance, as well as daily prescription opioid use and daily heroin injection drug use. These findings underscore a need to reduce potential barriers to MMT retention by providing access to stable housing and preventing treatment interruptions during transitions between community and custodial settings.

Assessment of interfering factors and clinical risk associated with discontinuation of pemetrexed maintenance therapy in advanced non-squamous non-small cell lung cancer

ObjectivesPemetrexed continuation maintenance therapy after induction with platinum-based chemotherapy is a standard treatment option for non-squamous non-small cell lung cancer (NSCLC) patients. However, discontinuation of maintenance therapy is still a challenge in clinical practice. We aimed to investigate interfering factors and clinical risk associated with discontinuation of pemetrexed maintenance therapy (PMT). Materials and methodsData of patients with locally advanced or metastatic non-squamous NSCLC who received PMT between December 2011 and October 2015 were retrospectively analyzed. Patients’ characteristics, performance status (PS), response and toxicity evaluation were collected. The reasons for PMT discontinuation were summarized. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan–Meier method and Cox proportional hazard model. ResultsOf the 220 patients included for final analysis, 132 patients (60.0%) continued PMT until disease progression. The patients over 60 years old (p=0.021), the patients with PS 2 at the initiation of PMT (p=0.005) and the patients experienced grade 3/4 toxicity during PMT (p<0.001) had a higher discontinuation rate. The reasons for PMT discontinuation were the regarding toxicity (39.8%), high intensity of hospital visit (17.0%), treatment cost (13.6%), patients’ preference (26.1%) and failure of pain control (3.4%). In univariate analysis, PS 0–1 at the initiation of PMT (5.6 versus 4.3 months, p=0.022) and PMT continuation (5.6 versus 4.3 months, p<0.001) were associated with improved PFS. And PMT continuation was associated with improved OS (19.2 versus 16.8 months, p=0.003) along with actionable mutations and PS 0–1 at the initiation of PMT. In multivariate analysis, PMT continuation (hazard ratio: 1.486; 95% CI: 1.050–2.104; p=0.025) was an independent prognostic factor regarding OS benefit assessed by Cox proportional hazard model. ConclusionDiscontinuation of PMT is common in clinical practice. The survival benefit suggests that fit patients should be encouraged to continue PMT until disease progression.