Months Of Maintenance Therapy Research Articles

RMS13: A phase II trial using risk adapted focal proton beam radiation and/or surgery with the addition of maintenance chemotherapy in intermediate risk rhabdomyosarcoma.

10008 Background: European trials have demonstrated improved outcomes in SIOP high-risk/COG intermediate risk (IR) rhabdomyosarcoma (RMS) when 6 months of maintenance therapy (MTC) was added to ifosfamide, vincristine (VCR), dactinomycin (DAC) +/-doxorubicin chemotherapy. The effectiveness of MTC integrated with VCR, DAC and cyclophosphamide (CYC), standard North American chemotherapy, remains unclear. Methods: RMS13 is a phase II multicenter trial evaluating the safety and efficacy of risk adapted proton radiation therapy (RT) and the addition of MTC in patients with IR RMS (embryonal stage 1, Group III non-orbit, and stage 3 Group I, II were not eligible for MTC). Patients received 12 cycles of VCR (1.5mg/m2 weekly), DAC (0.045mg/kg q3weeks), and CYC (1200mg/m2 q3weeks) (VAC) followed by MTC with 4 cycles of oral CYC (50mg/m2 daily), bevacizumab (15mg/kg) q3wks, and sorafenib (90mg/m2 bid) (CBvSor). RT was prescribed based on local tumor status at the time of RT (Table 1). Five-year disease-free survival (DFS) using the Kaplan-Meier method and the cumulative incidence (CI) of primary site local failure (LF) was described. Results: 46 patients were enrolled (Table 1). One patient refused further therapy and was removed from the analysis. 5-year DFS for the entire cohort was 67.5% with a median follow up of 54 mo. The trial was halted since < 75% of enrolled patients received all prescribed CBvSor MTC. Of the 35 who were eligible for MTC, 24 initiated MTC and 18 completed protocol-directed MTC. Three pts received vinorelbine/CYC MTC after enrollment was stopped. Reasons for not completing CBvSor MTC included: progression prior (6), toxicity (5), refusal (3). The 5-year DFS for the 24 patients that started cycle 3 was 70.3%. When limited to patients classified as high-risk in RMS2005 trial, the 5-year DFS was 81.4%. No patients experienced LF after margin negative surgery. The CI of LF was: 0% following 36GyRBE RT for microscopic residual disease, 8% for patients with unresected tumors < 5cm receiving standard dose RT (50.4GyRBE), and 10% for patients with unresected tumors > = 5cm receiving dose escalated RT (59.4GyRBE). 5/6 patients with alveolar N1 disease recurred. Conclusions: Local control with risk adapted dose-escalated RT was excellent in IR patients. Those with nodal involvement fared poorly. While 4-cycles of MTC with CBvSor was not feasible, those who underwent at least 3 cycles experienced enhanced DFS outcomes, aligning with the positive results seen in other trials incorporating MTC. Clinical trial information: NCT01871766 . [Table: see text]

The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia.

Polymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL). This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated. A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity. Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.

Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study

BackgroundType 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation.MethodsWe analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18–36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors.ResultsAfter discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001).ConclusionsA high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Efficacy of a medical grade honey formulation (L-Mesitran) in comparison with fluconazole in the treatment of women with recurrent vulvovaginal candidiasis: protocol for a randomised controlled trial (HONEY STUDY)

IntroductionRecurrent vulvovaginal candidiasis (RVVC) affects up to 9% of women worldwide. This amount is expected to increase due to lifestyle changes, increased fungal resistance and biofilm formation. Treatment options are...

Persistence and Dose Escalation During Maintenance Phase and Use of Nonbiologic Medications Among Patients With Ulcerative Colitis Initiated on Ustekinumab in the United States.

Real-world data on treatment patterns among patients with ulcerative colitis (UC) initiated on ustekinumab are limited. Adults with UC initiated on ustekinumab (index date) between 10/18/2019 and 04/31/2022 were selected from a deidentified health insurance claims database (Symphony Health, an ICON plc Company, PatientSource). Persistence (no gaps in days of supply >120 days), persistence while being corticosteroid-free (no corticosteroid use for ≥14 days of supply after a 90-day grace period from index date) and dose escalation (≥2 consecutive subcutaneous claims ≥100% above daily maintenance dose) were described during the maintenance phase using Kaplan-Meier analysis. Nonbiologic treatments, among patients with ≥2 ustekinumab claims within 90 days post-index and ≥6 months of follow-up, were compared with logistic models 6 months post- versus pre-ustekinumab initiation. 6565 patients on ustekinumab entered the maintenance phase. At month 12 of the maintenance phase, 72.0% (95% confidence interval [CI]: 70.1%-73.9%) were persistent, 50.8% (95% CI: 48.7%-52.9%) were persistent and corticosteroid-free, and 19.2% (95% CI: 17.3%-21.3%) of patients had dose escalation. In the 6 months post- versus pre-ustekinumab initiation, the odds of nonbiologic medication use assessed in 4147 patients were significantly lower: 57% lower odds for corticosteroid, 46% for 60 cumulative days of corticosteroid, 42% for 5-aminosalicylic acid, and 24% for immunomodulators (all P < .001). Most patients with UC reaching the maintenance phase on ustekinumab remained persistent after 12 months of maintenance therapy. Nonbiologic medication use post-ustekinumab initiation was significantly lower, notably for corticosteroids. Given the multiple complications associated with chronic corticosteroid use, this reduction can be seen as clinically relevant and informs treatment choice for patients with UC.

Pitfalls in the diagnosis of Cryptococcal Meningoencephalitis. (P1-10.001)

<h3>Objective:</h3> We report a case of cryptococcal meningoencephalitis which challenges the prevailing theory of antigen detection being more sensitive for the diagnosis than CSF biofire. <h3>Background:</h3> 60 year old immunocompetent male was admitted with episodes of unsteady gait, staring and picking at his clothes. Examination revealed lethargy and constructional apraxia. MRI brain showed ventriculomegaly. CSF analysis showed opening pressure 34cm H2O, protein 134, WBC count 62 with 98% lymphocytes. CSF multiplex PCR panel and Cryptococcal antigen were negative. He was started on Topiramate and Acetazolamide. As he did not improve, repeat lumbar puncture was obtained six days after admission. Repeat CSF PCR panel was positive for cryptococcal DNA, however both serum and CSF cryptococcal antigen were negative. CD4 count was 977 cells/uL. He was started on induction therapy for Cryptococcal meningoencephalitis. A lumbar drain was placed for secondary hydrocephalus. He completed 12 months of maintenance therapy and is doing well on follow up. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Detection of the capsular antigen by lateral flow assay has widely been believed to be the most reliable diagnostic method for Cryptococcal Meningoencephalitis. The cryptococcal antigen in the specimen diluent binds to gold conjugated anticryptococcal monoclonal antibodies on the test strip, producing a detection line. This test is based on an optimal antigen-antibody ratio, known as the zone of equivalence. A false negative result might be obtained in case of antigen levels greater than 0.14 mg/L (postzone phenomenon), as the excess antigen binds colloidal gold instead of immobilized antibody in the test area of the strip. Hospital laboratories do not routinely test for this occurrence, which can lead to a missed diagnosis. <h3>Conclusions:</h3> Using a greater dilution ratio of 1:5 (semi quantitative) or 1:9, instead of 1:2 (qualitative) can bring the antigen titer in the zone of equivalence. Using an alternate diagnostic method such as CSF biofire is another option. <b>Disclosure:</b> Dr. Nene has nothing to disclose. Dr. Mahapatra has nothing to disclose. Dr. Duleep has nothing to disclose.

Mania as a Result of Using Disulfiram at the Prescribed Amount During the Fifth Month of Maintenance Therapy: A Case Report

Mania as a Result of Using Disulfiram at the Prescribed Amount During the Fifth Month of Maintenance Therapy: A Case Report

Clinical Trial to Assess Physiology and Activity of Masticatory Muscles of Complete Denture Wearer Following Vitamin D Intervention.

Background and Objectives: Little information is available on the role of Vitamin D as a micro-nutrient deficiency with masticatory muscle efficiency and its effect on the function of removable prosthesis. The aim of this study was to evaluate the role of vitamin D on masticatory muscle activity among completely edentulous patients and its effect on the retention of removable complete dentures (RCDs). Materials and Methods: A non-randomized clinical control trial was conducted on completely edentulous patients (60.53 ± 7.01 years) in the Indian population between 2017 and 2019. Subjects were evaluated for temporomandibular disorders according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Serum Vitamin D (S Vit D) levels, Ultrasonography (USG), and surface Electromyography (sEMG) readings of the masseter muscle were recorded at enrolment (Level 0), after 3 months of Vitamin D therapy (Level 3), and after consecutive 3 months of maintenance therapy, i.e., after 6 months from baseline (Level 6). The fabrication of new RCDs was done for all after the enrolment, and the retention of RCDs was assessed by asking a question regarding denture retention and asking respondents to mark their satisfaction on a 5-point Likert scale. Data were analysed using ANOVA, Paired'-test and Pearson correlation coefficients. A p-value less than 0.05 indicated a statistically significant association. Results: Between enrolment and a six-month follow-up, S Vit D levels showed an increase from 16.03 ± 5.68 ng/mL to 31.35 ± 9.28 ng/mL, showing an increase of 15.32 ± 9.38 ng/mL (95.57% rise). Statistically significant values were observed for USG and sEMG. Conclusions: Results showed that S Vit D affects masticatory muscle activity by improving its thickness and boosting its tonicity. Healthy muscles assist in the retention of RCDs, consequently aiding in mastication, speech, and phonetics, hence improving patient satisfaction. Clinical implication: Acknowledging the fact that the prevalence of Vitamin D deficiency is worldwide. We suggest Vitamin D therapy as a nutritional intervention among the elderly completely edentulous population, following dietary counselling, and consider Vitamin D therapy to be an adjunct to nutritional counselling for improving masticatory muscle activity and efficiency, which aids in RCD retention and stability. Consequently, improving oral health-related quality of life for individuals.

EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy

AbstractThe development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus–driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm– and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P = .01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.

Role of PARP Inhibitors in Glioblastoma and Perceiving Challenges as Well as Strategies for Successful Clinical Development.

Glioblastoma multiform is the most aggressive primary type of brain tumor, representing 54% of all gliomas. The average life span for glioblastoma multiform is around 14–15 months instead of treatment. The current treatment for glioblastoma multiform includes surgical removal of the tumor followed by radiation therapy and temozolomide chemotherapy for 6.5 months, followed by another 6 months of maintenance therapy with temozolomide chemotherapy (5 days every month). However, resistance to temozolomide is frequently one of the limiting factors in effective treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have recently been investigated as sensitizing drugs to enhance temozolomide potency. However, clinical use of PARP inhibitors in glioblastoma multiform is difficult due to a number of factors such as limited blood–brain barrier penetration of PARP inhibitors, inducing resistance due to frequent use of PARP inhibitors, and overlapping hematologic toxicities of PARP inhibitors when co-administered with glioblastoma multiform standard treatment (radiation therapy and temozolomide). This review elucidates the role of PARP inhibitors in temozolomide resistance, multiple factors that make development of these PARP inhibitor drugs challenging, and the strategies such as the development of targeted drug therapies and combination therapy to combat the resistance of PARP inhibitors that can be adopted to overcome these challenges.

Epidemiology and outcomes of acute promyelocytic leukaemia in the era of all-trans retinoic acid (ATRA) chemotherapy and arsenic trioxide plus ATRA: a retrospective analysis

Acute promyelocytic leukaemia (APL) results from the reciprocal chromosomal translocation t(15;17)(q24;21) (PML-RARA gene fusion). We have formulated an oral, economical, and outpatient-based preparation of arsenic trioxide and shown that it is efficacious for newly diagnosed and relapsed APL. In this study, we aimed to define the epidemiological landscape of APL in Hong Kong and to assess the effect of oral arsenic trioxide therapy on patient outcomes. This retrospective analysis of patients diagnosed with APL in Hong Kong between Jan 1, 1991, and March 31, 2021 (data censored on Nov 30, 2021) had incidence of APL, early death (within 30 days of hospitalisation), and overall survival as primary outcomes, and incidence of other primary cancers as a secondary outcome. Oral all-trans retinoic acid (ATRA) plus chemotherapy or oral arsenic trioxide were used. ATRA plus chemotherapy comprised induction with ATRA (45 mg/m2 per day, divided in two doses, for 42 days) and daunorubicin (50 mg/m2 per day intravenously for 3 days); consolidation with two cycles of daunorubicin (for 2 days) and cytarabine (100 mg/m2 per day intravenously for 5 days); and 24 months of maintenance therapy with ATRA (for 15 days every 3 months), 6-mercaptopurine (90 mg/m2 per day), and methotrexate (15 mg/m2 per week). The arsenic trioxide approach comprised two dosing schedules: for patients diagnosed between Jan 1, 2013, and Dec 31, 2017, arsenic trioxide was included in induction and maintenance only; induction was with arsenic trioxide (0·15 mg/day for 42 days), ATRA, oral ascorbic acid (1000 mg/day for 42 days), and daunorubicin; consolidation was with two cycles of daunorubicin and cytarabine; and 24 months of maintenance with arsenic trioxide, ATRA, and ascorbic acid (all for 14 days every 2 months). For patients diagnosed between Jan 1, 2018, and March 31, 2022, arsenic trioxide was included in induction, consolidation, and maintenance, substantially reducing exposure to chemotherapy; induction was with arsenic trioxide (0·15 mg/kg per day for 42 days), ATRA and ascorbic acid (for 42 days), and daunorubicin (given only to patients presenting with a leucocyte count of 10 × 109 cells/L); consolidation was with two cycles of arsenic trioxide, ATRA, and ascorbic acid (all for 14 days every 28 days); and 24 months of maintenance therapy with arsenic trioxide, ATRA, and ascorbic acid. Multivariate cox regression analysis was used to find prognostic indicators for overall survival. This schedule required a 21-day hospital stay during the induction phase, and consolidation and maintenance phases were entirely done in outpatient settings. This ongoing study was approved by the University of Hong Kong's Institutional Review Board and is registered with ClinicalTrials.gov, NCT04251754. 751 patients (387 [51%] women and 364 [49%] men) were identified (median age 44 years [IQR 31-57]), for an annual incidence of 0·32 per 100 000 people. 469 (62%) patients received ATRA plus chemotherapy and 282 (38%) patients received oral arsenic trioxide. After a median follow-up of 75 months (IQR 14-161), 271 (36%) patients had died, with early death constituting 144 (53%) cases, all occurring in patients in the ATRA plus chemotherapy cohort. 5-year overall survival in the full cohort was 68% and 10-year overall survival was 63%. On multivariate analysis, being male (p=0·019), older than 50 years (p<0·0001), having a leucocyte count of >10 × 109cells/L at presentation (p<0·0001), and having ATRA plus chemotherapy regimens (p<0·0001) were all associated with worse overall survival. In the oral arsenic trioxide cohort, 5-year overall survival was 92% and 10-year overall survival was 85%. In the ATRA plus chemotherapy cohort, 5-year overall survival was 55% and 10-year overall survival was 51%. Second cancers developed in 21 patients (eight never exposed to oral arsenic trioxide; 13 with previous exposure to oral arsenic trioxide during induction, maintenance, or relapse). The incidence of second cancers in patients exposed to oral arsenic trioxide did not differ from that in patients never exposed to oral arsenic trioxide (incidence rate ratio 2·14 [95% CI 0·89-5·17], p=0·099). Oral arsenic trioxide plus ATRA was associated with fewer early deaths and better long-term survival than ATRA plus chemotherapy, with shorter hospital stays and outpatient treatment as distinct health-care advantages. Health and Medical Research Fund of the Hong Kong Special Administrative Region, China (code 08191946).

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study

Purpose: Bacille Calmette-Guerin (BCG) is considered the most effective agent for non-muscle invasive bladder cancer (NMIBC). However, due to BCG-related toxicity, multiple studies have suggested the role of newer chemotherapeutic drugs. The aim of our study was to evaluate intravesical gemcitabine + docetaxel (Gem/Doce) versus BCG with respect to quality of life (QOL), safety, and efficacy in NMIBC. Methods: A total of 60 patients with NMIBC were evaluated between July 2019 and December 2020 in a prospective manner. The sample size calculation was done, keeping in mind the incidence of intravesical BCG-related complications of up to 50–60% and 20–30% for Gem/Doce combination. The p value of 0.05 was kept as statistically significant. The enrollment ratio was kept at 1, and power of study was aimed at 80%. The study population was alternatively assigned to two groups (BCG vs. Gem/Doce) of 30 patients each. Both the groups received 6 weekly doses of induction therapy followed by 6 monthly doses of maintenance therapy if no recurrence was noted at interim follow-up. QOL scores, safety, and efficacy were assessed at beginning of intravesical therapy, end of induction, and 6 months of maintenance therapy. Cystoscopy examination and cytology were performed at the end of induction therapy and 3-monthly thereafter. Result: The preliminary results at the end of 6 months following maintenance therapy showed that the demographic profile, histological stage, and grade were comparable between two groups. The QOL scores using QLQ-30 and QLQ-BLS-24 showed statistically significant differences with the Gem/Doce arm showing better outcomes. There were no progressions to higher stage, while one recurrence each was seen in both groups. Patient-related side effects measured by CTCAE (Common Terminology Criteria for Adverse Events)version 5 showed that the BCG group had higher toxicity profile as compared to Gem/Doce group. Conclusion: Gem/Doce combination intravesical therapy is a promising alternative to BCG for treatment of NMIBC, showing better QOL measures and lesser side effects.

Continuing posterior tibial nerve stimulation after twelve weekly sessions: a randomized controlled trial

Posterior Tibial Nerve Stimulation (PTNS) is a treatment option for refractory Overactive Bladder (OAB). There is currently no evidence to support which maintenance schedule is most effective. The objective of this study is to compare patientreported outcomes between monthly maintenance therapy and sessions scheduled Per patient request (PRN). We hypothesized that there is no difference in these measures between groups. After completing 12 sessions of PTNS, patients were randomized to monthly or PRN maintenance. Quality of life, patient satisfaction, and degree of symptom bother were assessed with validated questionnaires. Thirty six patients were randomized: 19 to monthly follow-up, and 17 to PRN follow-up. The PRN group demonstrated a significantly higher quality of life (p=0.04) with a large effect size (0.82). Over a three-month period, there was no significant difference in the average number of visits between the monthly and PRN groups, with an average of 1.79 (±1.18) and 1.24 (±1.35) visits, respectively (p=0.20). After six months of maintenance therapy, 42% of patients in the monthly group and 53% of patients in PRN group elected to continue therapy (p=0.27). There was no significant difference between the groups with regard to treatment satisfaction (p=0.62) or percent change in OAB symptoms (p=0.13). There is no difference between monthly and PRN follow-up in terms of patient satisfaction and symptom bother. However, the PRN group scored higher on the quality of life measure. PRN maintenance may optimize care for patients treating Overactive Bladder Syndrome with posterior tibial nerve stimulation.

Daratumumab Plus Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): A Subgroup Analysis of Griffin

Daratumumab Plus Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): A Subgroup Analysis of Griffin

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance

The Strategy of the Management of Patients with Chronic Lymphocytic Leukemia in the Post-Induction Period Based on the Results of the Evaluation of Minimal Residual Disease

Background. Although inclusion in the treatment programs of new drugs (including new monoclonal antibodies and targeted therapies) allowed the majority of patients with chronic lymphocytic leukemia (CLL) to achieve remission (complete or partial) after combined therapy virtually all patients relapse, presumably due to the persistence of minimal residual disease (MRD). There is strong evidence that the achievement of a negative status for MRD is the single most important factor predictive of final outcome in patients with CLL treated with chemoimmunotherapy. So, at now, the urgent task is long-term preservation and the deepening of the response, if it is possible. Continuing to administer rituximab to patients who respond to rituximab-based induction is possible option. Currently, there is no consensus about the need for maintenance therapy (MT) for patients with CLL.Aim. To estimate the importance of maintenance therapy of rituximab in the treatment of patients with CLL.Methods. Since January 2014, 83 patients were included in the study. Male to female ratio - 1.3:1. We have used NCI revised guidelines (Hallek M., et al., 2008) for treatment initiation, assessment of response and MRD. Induction chemotherapy was conducted under the following programs: RB, RFC, R-CHOP. Evaluation of MRD was performed using 5-color flow cytometry of the bone marrow cells. For the study, we developed an algorithm of patient management in post-induction period on the basis of the results of MRD evaluation. Group 1 (n=23): patients with MRD-negative remissions who were under dynamic observation (without therapy) every 3 month with mandatory evaluation of MRD. Group 2 (n=60): patients with MRD-positive remissions who received MT of Rituximab 500 mg/m2 intravenously every 8 weeks for 2 years. Another 48 patients (Control group) with MRD-positive remissions did not receive MT. MT was began if MRD was detected in the patients from Group 1 within 1 year after the end of chemotherapy, they began maintenance therapy.Results. Median observation was 18.8 month (5 - 36). The increasing the depth of response (from partial to complete remission) was observed only in group of patients receiving MT - 11.7%. MRD was not detected after 6-12 months of MT in 21.7% (13/60) patients from Group 2.The frequency of relapses in Group 1 was 52.2% (12/23), in Group 2 - 33.3% (20/60), in Control group - 81.3%. Significant differences were detected between Group 1 and Control group (p=.01) and Group 2 and Control group (p˂.0001). Median progression-free survival was not reached in the rituximab maintenance group, in the Group 2 was 30.4 month (p˃.05) and in the Control group - 24.3 month (p=.02).MT was begun in the 5 patients from Group 1 because MRD was detected in the first year of observation, but the symptoms of progression disease were absent. After 12 months, 2 patients achieved MRD-negative status.Significant differences in the incidence of infectious complications between patients with MT and without of MT were not detected (p˃.05).Conclusion. The conducting of MT patients with CLL allows to achieve increasing the depth achieved remission (clinical and molecular) and increase the duration of its preservation. MT with rituximab may be a means of control over the minimal residual disease and the method of its eradication. The proposed algorithm need further testing to confirm the initial results. DisclosuresShuvaev:Fusion Pharma LLC: Consultancy.

Pneumocystis Jiroveci Pneunomia Prophylaxis during Maintenance Therapy with Hyper-CVAD Regimens for Adult Acute Lymphoblastic Leukemia

BACKGROUNDPneumocystis jiroveci pneumonia (PCP) can be a deadly opportunistic infection in immunocompromised patients. Patients with acute lymphoblastic leukemia (ALL) are at risk for PCP due to their underlying disease, use of high doses of corticosteroids and receipt of lymphocyte-depleting chemotherapy. It is recommended that patients receive PCP prophylaxis during treatment for ALL. Trimethoprim/sulfamethoxazole (TMP/SMZ) is a common agent utilized but some practitioners are concerned about myelosuppression induced by TMP/SMZ. HyperCVAD regimens are the standard treatment strategy for ALL patients at our institution. Historically, PCP prophylaxis with TMP/SMZ was delayed until the beginning of maintenance therapy. This retrospective analysis evaluated PCP prophylaxis and incidence in ALL patients receiving maintenance therapy on a HyperCVAD regimen. Any influence of PCP prophylaxis on clinical outcomes was also evaluated. METHODSNewly diagnosed adult (≥ 18 yo) patients with ALL or lymphoblastic lymphoma who received at least one cycle of maintenance therapy on a HyperCVAD regimen between April 2000 to December 2016 were reviewed. Interim chart reviews were performed to identify the use of PCP prophylaxis and definite or suspected cases of PCP, as well as to document maintenance therapy doses or change in patient status, until the completion of maintenance therapy. Suspected PCP cases (missing microbiological documentation of Pneumocystis) were defined as those patients receiving PCP active therapy based on clinical presentation and imaging. RESULTSDuring the study period, 363 frontline ALL patients received at least one cycle of HyperCVAD maintenance therapy. 346 (198 males and 148 females) patients had sufficient documentation. Of these 346 patients, 145 never received PCP prophylaxis, 67 received i ntermittent PCP prophylaxis, and 134 received uninterrupted PCP prophylaxis throughout maintenance therapy. Only 3 cases of PCP (0.9%) were identified, one confirmed and 2 suspected. All cases occurred within the first 6 months of maintenance therapy and in patients never receiving PCP prophylaxis. The majority of patients receiving prophylaxis were on TMP/SMZ (97%); the most common regimen was 160 mg of the TMP component (1 DS tablet) twice daily two days per week. PCP prophylaxis rates have decreased over time - 55% of patients received uninterrupted PCP prophylaxis if initiated ALL maintenance therapy in 2000-2005 versus 10% of patients received uninterrupted maintenance if initiated ALL maintenance therapy in 2010-2016 (p=<0.001). Philadelphia-positive patients (106/346, 31%) received TKI-based maintenance therapy (TKI, corticosteroid, vincristine). Philadelphia-positive patients were less likely to receive uninterrupted PCP prophylaxis (p<0.0001). Doses of TKI were not statistically different between PCP prophylaxis groups. Philadelphia-negative patients received maintenance therapy containing mercaptopurine and methotrexate (plus corticosteroid, vincristine). Doses of mercaptopurine and methotrexate were not statistically different between PCP prophylaxis groups (p=0.75, p=0.4 respectively). ANC values were analyzed over time and were not significantly different between PCP prophylaxis groups (p=0.36 for never versus uninterrupted PCP prophylaxis). ALC values were also evaluated and were significantly lower in the uninterrupted PCP prophylaxis group at baseline, maintenance year 1 and maintenance year 2 (p=0.0464, p=0.0002, p=0.0001 respectively). Relapse rate, PFS and OS did not differ between the never, intermittent and uninterrupted PCP prophylaxis groups. CONCLUSIONSThe rate of PCP was low in this group of adult patients with newly diagnosed ALL undergoing maintenance therapy as part of a HyperCVAD regimen. All PCP cases occurred in patients not receiving PCP prophylaxis. TMP/SMZ prophylaxis had no significant effect on doses of ALL maintenance therapy provided as well as PFS and OS. TMP/SMZ remains a safe, effective choice for PCP prophylaxis in adult ALL patients. Given the low incidence of PCP in this population, future studies are warranted to identify risk factors that allow selection of patients who would benefit the most from PCP prophylaxis. DisclosuresJabbour:Bristol-Myers Squibb: Consultancy.

Maintenance acne therapy: prophylactic efficacy of fixed combination of adapalene and benzoyl peroxide

Acne is a chronic disease and even reliable therapies do not completely ensure absence of relapses. Acne relapses have a negative psychological impact on patients, as they feel unable to control the disease and achieve complete and long-lasting recovery. Supportive therapy is necessary to prolong the remission of acne achieved with initial successful treatment and to minimize the risk of relapse. According to the literature sources, the most justified as a maintenance therapy is the use of topical retinoids, which have been shown to be effective in the prevention of exacerbations of acne. In the present study 54 patients were involved who after the active therapy used a fixed combination of adapalene 0.1% / BPO 2.5% as maintenance treatment. Only 1 patient (2.9%) with moderate acne and 2 patients (5.8%) with severe acne had a relapse within 6 months of maintenance therapy. The absence of adverse events during the course of treatment was recorded, as well as high adherence of patients to the treatment. During the period of post-treatment observation (6 months after maintenance therapy), among the patients without exacerbations during maintenance therapy, a relapse occurred in 2 (7.1%) patients of group 1 (n = 28) and 2 (8.7%) patients of group 2 (n = 23). The obtained data indicates that maintenance therapy with Effezel® gel can extend the achieved effectiveness of the treatment and prevent the development of relapses.

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy

The Impact of Sorafenib on Phospho-FLT3 Inhibition and FLT3-ITD MRD after Chemotherapy: Correlative Studies from the Phase 2 Randomized Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)

The Impact of Sorafenib on Phospho-FLT3 Inhibition and FLT3-ITD MRD after Chemotherapy: Correlative Studies from the Phase 2 Randomized Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)