Outcomes Of Second-line Therapy Research Articles

Outcomes of Second Line Therapy for Light Chain Amyloidosis after Initial Therapy with a Bortezomib Based Regimen

Introduction: There are a lack of randomized trials to guide therapy for relapsed AL amyloidosis with treatment regimens generally extrapolated from experience in multiple myeloma. Methods: We conducted a retrospective review of bortezomib exposed patients that received second line therapy for AL amyloidosis at three Amyloidosis centres in Australia (Brisbane, Perth and Sydney). Of 190 patients treated with bortezomib based therapy upfront, 98 (52%) had transitioned to second line therapy during the study period and comprised the study cohort. Results: Baseline characteristics for the study cohort were typical for a cohort with AL amyloidosis. Median age was 66 years, with 38% of patients being male. Cardiac and renal involvement was present in 70% of patients respectively. Seven patients (7%) had frontline therapy that included daratumumab. Median duration of frontline therapy was 5 months (range 2-18 months) and median time from diagnosis to second line therapy was 9 months (range 2-65 months). We categorized treatment regimens according to commonly used combinations and drug classes to further analyse outcomes. Six categories of therapy regimens were identified; autologous stem cell transplant (ASCT) (n=17), thalidomide based (n=12), lenalidomide based (n=13), proteasome inhibitor (PI) based (n=9), Anti-CD38 monoclonal antibody (mAB) based (n=38) and melphalan based (n=4). Five patients were excluded from this analysis as they received an atypical therapy/regimen not commonly used for AL amyloidosis. Overall response rate (ORR) for the whole cohort was 84%. The ORR was lowest for thalidomide and melphalan based therapy (67% and 50% respectively) and highest for patients receiving an ASCT or anti-CD38 mAB therapy (94% and 92% respectively), Figure 1a. Median event free survival (EFS) for the cohort from second line therapy was 17 months. Median duration of follow up from second line therapy for the cohort was 26 months . Median EFS was shortest for patients treated with thalidomide and melphalan based regimens (6 and 12 months respectively) and longest for those who received an ASCT (28 months) or anti- CD38 mAB therapy (not reached), Figure 1b. When comparing immunomodulatory drugs lenalidomide treated patients had a longer EFS (median 6 months for thalidomide vs 16 months for lenalidomide, p=0.09). The median overall survival (OS) for the cohort was 81 months. OS was longest amongst patients receiving an ASCT or anti-CD38 mAB therapy (median of 91 months and not reached, respectively). Survival was similar amongst patients treated with a PI or Immunomodulatory drug (median 41 months for thalidomide, 44 months for lenalidomide and 36 months for PI based therapy). Conclusion: In bortezomib exposed AL amyloidosis patients, second line therapy with anti CD38 mAB's induced deep responses and prolonged survival. Amongst immunomodulatory agents, the second generation agents appear to be more effective. In our cohort the small group of patients receiving repeat therapy with a PI also appeared to respond to treatment. Although an intensive treatment with significant risks, our data show that in select individuals an ASCT can induce deep and long lasting remissions. Our data highlights the variability in second line therapies for AL amyloidosis given the paucity of evidence to guide treatment. The recent addition of daratumumab as a standard of care for upfront therapy further limits options in the relapsed setting and highlights the need for trials using next generation novel anti plasma cell agents in this patient population.

Outcome of second-line treatment after CDK4/6 inhibitors in hormonal-positive HER-2 negative metastatic breast cancer: Single institution experience.

e13053 Background: In patients with metastatic hormonal receptors (HR)-positive, HER2-negative breast cancer, CDK 4/6 inhibitors with hormonal therapy is the current standard first line therapy in patients without visceral crisis. Limited data is available about the outcome of second line therapy after CDK 4/6 inhibitors. In this study, we reported the survival outcome of second line systemic therapy after CDK 4/6 inhibitors in a single institute in Saudi Arabia. Methods: We retrospectively checked patients with metastatic HR-positive, HER2-negative breast cancer who received first line therapy with palbociclib in addition to an aromatase inhibitor in King Abdullah Medical City, Saudi Arabia. Patients who received second line systemic therapy were recruited. Different clinicopathological data were checked in addition to type of second line therapy, dates of starting 1st and second lines therapy and dates of progression. We check progression-free survival (PFS) with second line therapy in relation to the type of second line therapy, duration of 1st line therapy and other potential prognostic factors. Results: We recruited 59 eligible patients. Median PFS of the study group was 4 months (95% CI 2.9-5.1). No significant difference in PFS according to type of second line systemic therapy (chemotherapy: 4 months, everolimus with hormonal therapy: 6 months, hormonal monotherapy: 3 months, p=0.17). In addition, there was no significance difference in second line therapy PFS according to duration of 1st line palbociclib-hormonal therapy (≤ 12 months: 4 months vs. >12 months: 5 months, HR 0.97, 95% CI: 0.55-1.7, p=0.92). Similarly, taking 6 months as a cutoff, no significant difference in PFS (≤ 6 months: 4 months, >6 months: 6 months, HR 0.73, 95% CI: 0.43-1.24, p=0.25). Similarly, no difference in second line PFS according to menopausal status, age at diagnosis (≤ 50 vs >50) or ER-Allred score (≤ 6 vs >6). Conclusions: Outcome of 2nd line systemic therapy following first line palbociclib with hormonal therapy was poor in the study cohort. No significant difference in PFS according to type of systemic therapy, duration of first line therapy, or other clinicopathological factors.

Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly

IntroductionTreatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes.Patients and methodsA retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V).ResultsThirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02).ConclusionOur data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.

Treatment failure, death, and predictors among PLWHIV on second-line antiretroviral therapy in Dessie Comprehensive Specialized Hospital, northeast Ethiopia: A retrospective cohort study.

BackgroundThe proportion of HIV patients on second-line antiretroviral therapy is becoming a growing public health concern, especially in a low-income country setting. However, unlike first-line therapy, to date, very little is known about the outcomes of second-line therapy in the Ethiopia context. Thus, this study was conducted to determine the rate of treatment failure, death, and their predictors among HIV patients receiving second-line therapy.MethodsA retrospective cohort study was conducted on 642 people living with HIV in Dessie Comprehensive Specialized Hospital from October 2016 to November 2019. Poisson and competitive risk survival models were computed to explore predictors of treatment failure and death, respectively.ResultsDuring follow-up period, 39 (6.87%, 95% CI: 5–9.2%) of 568 patients had second-line treatment failure with 4.07 per 100 person-year rate of failure. Being on anti-TB treatment [Rate ratio, RR = 2.57 (95% CI: 1.25–5.25)], not having optimal medication adherence [RR = 2.29 (95% CI: 1.09–4.78)], and not timely switched [RR = 5.89 (95% CI: 1.36–25.54)] were positively associated with treatment failure. Similarly, 44 (6.85%, 95% CI: 5–9%) of 642 patients died with 4.5 per 100 person-year rate of death. Being on advanced clinical condition [Sub distribution Hazard ratio, SHR = 2.49 (95% CI: 1.31–4.74)], not having optimal medication adherence [SHR = 2.65 (95% CI: 1.31–4.74)], lower CD4 cell counts, and high viral load measurement were positively associated with death.ConclusionsA significant number of patients had failed to respond to second-line therapy. A large number of patients had also died. Patient medical profile and monitoring practice were associated with treatment failure and death. Hence, patient-centered monitoring and interventions should be strengthened, besides treatment switch.

Outcomes of second-line therapies in patients with metastatic de novo small cell prostate cancer (SCPC) and treatment-emergent neuroendocrine prostate cancer (tNEPC).

e17022 Background: De novo SCPC and tNEPC in metastatic castrate resistant prostate cancer (mCRPC) are rare, aggressive cancers with a poor prognosis. After first-line (1L) platinum chemotherapy (PLT), there is no consensus on 2L treatments. This multi-institutional, retrospective study examines practice patterns among clinicians and evaluates the outcomes of patients (pts) with SCPC or tNEPC in the 2L setting. Methods: After IRB approval, pts with a pathologic diagnosis of SCPC or tNEPC (any % of SC or NE histology defined by institutional review) were identified. Pts diagnosed between 2000-2020 who received 1L PLT and any 2L systemic therapy (tx) for SCPC or tNEPC were included. Standardized data collection templates containing demographic, clinical, and pathologic variables were collected. The primary endpoint was objective response rate (ORR) to 2L tx. Secondary endpoints included PSA response, time on 2L treatment, and overall survival (OS) from time of 2L tx. Data was analyzed using descriptive statistics. Results: Forty-two pts (21 SCPC, 21 tNEPC) from 6 institutions were included. At SCPC/tNEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 60.5, 68.0) and median PSA of 3.0 ng/dL (IQR 0.5, 21.8). The most common sites of metastasis included lymph node (78.6%), bone (54.8%), and liver (52.4%). For 1L tx, 37 pts (88.1%) received PLT and 5 (11.9%) had PLT + immunotherapy (IMM). For treatment to the prostate, 21 (51.2%) had none, 7 (17.1%) radiation (RT), 9 (22.0%) surgery, 3 (7.3%) RT + surgery, and 1 (2.4%) brachytherapy alone. Concurrent ADT was given to 32 pts (76.2%) in the 1L and 2L. At last follow-up, 34 pts (81.0%) were dead, 4 (9.5%) were alive, and 4 (9.5%) were lost to follow-up/censored. For 2L tx, 10 pts (23.8%) received PLT, 8 (19.0%) taxane monotherapy (TAX), 10 (23.8%) IMM, 8 (19.0%) other chemotherapy (CHX), and 6 (14.3%) other tx. Among 38 pts evaluable for response, the ORR was 15.8% (6 pts with PR: 4 PLT, 1 IMM, 1 CHX). PSA response ≥ 50% to 2L tx was seen in 5 of 29 pts with PSA data (17.2%). Other outcomes data are reported in Table. Conclusions: In this retrospective study, pts with SCPC or tNEPC who reached 2L tx received a wide variety of treatment regimens, reflecting the lack of consensus in this tx setting. ORR was low and overall prognosis was poor in the 2L regardless of tx choice. Pts on 2L immunotherapy seemed to have the shortest mOS. [Table: see text]

Treatment Patterns and Outcomes of Second-Line Therapy in Adult Immune Thrombocytopenia: A Provincial Retrospective Cohort Study

Treatment Patterns and Outcomes of Second-Line Therapy in Adult Immune Thrombocytopenia: A Provincial Retrospective Cohort Study

An Interim Analysis of the Turkish Myeloma Registry Among the Patients Who Have Received up to Two Lines of Therapy

Introduction: To investigate the demographics and treatment details of the myeloma patients who were diagnosed and followed up in Turkey and received up to two lines of therapy.Methods: Patients who were recorded on the database of Turkish Myeloma Registry project were included in this study if they had only received one or two lines of therapy. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented.Results: A total of 532 patients were included in the study, and 44% of the patients were female. Median age at the time of diagnosis was 63 (30-106). 47.7% of the patients were diagnosed with IgG myeloma. According to the ISS risk stratification, 20.4% of patients had ISS 1, 34.7% of patients had ISS 2 and remaining 44.9% had ISS 3 disease. Defining high risk disease as harboring one or more of these following cytogenetic abnormalities; del 17p, t(4;14), t(14;16) or t(14;20); 7.1% of the patients were classified as having a high risk disease. Most commonly used frontline therapy approach was bortezomib cyclophosphamide dexamethasone combination (VCD) (76.5%) and followed by bortezomib dexamethasone (VD) (8.8%), and bortezomib lenalidomide and dexamethasone combination (VRd) (7.1%). Overall response rates (a better response than stable disease according to IMWG response assessment criteria) were 87.6% in VCD induced patients; 63.3% in VD induced patients and 92% in VRd induced patients. The PFS obtained by these frontline approaches was 17.8 months in patients who were able to proceed with high dose chemotherapy with ASCT support and 8.4 in patients who were not able to (p<0.01), with an overall PFS of 15.3 months. With regard to the induction approach, PFS was 21.1 months for VRD, 15.3 months for VCD and 7.6 months for VD (p=0.08). Regarding maintenance, 23.6% of patients were maintained by lenalidomide alone, 62.7% of patients were maintained by a combination of lenalidomide and dexamethasone or bortezomib alone (2.7%). PFS after the first line of the treatment was 22.2 months in maintained patients and 12.2 in un-maintained patients (HR: 0.532, p=0.001, CI95% 0.359-0.790). Regarding the second line therapy Rd was the leading option (34.8%) and VRd (17.8%), Carfilzomib based (16.3%), VCD (8.1%) were the followings.Conclusion: As the main concern of this study was to document the demographic features and clinical parameters of a Turkish Myeloma population and to give an idea about the treatment patterns and outcomes in frontline setting and first relapse an overall survival was not calculated. Progression free survival obtained after frontline therapy was relatively shorter than the ones which were presented by other real- world registries. Outcomes of second line therapy will be presented as follow up after 2nd line therapy exceeds a certain threshold. We hope, the results obtained from this study can have a role in the approval and re-imbursement of the current standard of care options. DisclosuresNo relevant conflicts of interest to declare.

P-125: An interim analysis of the Turkish Myeloma Registry among patients who have received up to two lines of therapy

<h3>Background</h3> To investigate the demographics and treatment details of the myeloma patients who were diagnosed and followed up in Turkey and received up to two lines of therapy. <h3>Methods</h3> Patients who were recorded on the database of Turkish Myeloma Registry project were included in this study if they had only received one or two lines of therapy. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. <h3>Results</h3> A total of 532 patients were included in the study 44% of the patients were female. Median age at the time of diagnosis was 63 (30-106). 47.7% of the patients were diagnosed with IgG myeloma. According to the ISS risk stratification, 20.4% of patients had ISS 1, 34.7% of patients had ISS 2 and remaining 44.9% had ISS 3 disease. Defining high risk disease as harboring one or more of these following cytogenetic abnormalities; del 17p, t(4;14), t(14;16) or t(14;20); 7.1% of the patients were classified as having a high risk disease. Most commonly used frontline therapy approach was bortezomib cyclophosphamide dexamethasone (VCD) (76.5%) and followed by bortezomib dexamethasone (VD) (8.8%), VRd (7.1%). Overall response rates (a better response than stable disease) were 87.6% in VCD induced patients; 63.3% in VD induced patients and 92% in VRd induced patients. The PFS obtained by these frontline approaches was 17.8 months in patients who were able to proceed with high dose chemotherapy with ASCT support and 8.4 in patients who were not able to (p<0.01), with an overall PFS of 15.3 months. With regard to the induction approach, PFS was 21.1 months for VRD, 15.3 months for VCD and 7.6 months for VD (p=0.08). Regarding maintenance, 23.6% of patients were maintained by lenalidomide alone, 62.7% of patients were maintained by a combination of lenalidomide and dexamethasone or bortezomib alone (2.7%). PFS after the first line of the treatment was 22.2 months in maintained patients and 12.2 in un-maintained patients (HR: 0.532, p=0.001, CI95% 0.359-0.790). Regarding the second line therapy Rd was the leading option (34.8%) and VRd (17.8%), Carfilzomib based (16.3%), VCD (8.1%) were the followings. <h3>Conclusion</h3> As the main concern of this study was to document the demographic features and clinical parameters of a Turkish Myeloma population and to give an idea about the treatment patterns and outcomes in frontline setting and first relapse an overall survival was not calculated. Progression free survival obtained after frontline therapy was relatively shorter than the ones which were presented by other real-world registries. Outcomes of second line therapy will be presented as follow up after 2nd line therapy exceeds a certain threshold. We hope, the results obtained from this study can have a role in the approval and reimbursement of the current standard of care options.

Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer.

In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.

Rate of Viral Re-Suppression and Retention to Care Among PLHIV on Second-Line Antiretroviral Therapy at Dessie Comprehensive Specialized Hospital, Northeast Ethiopia: A Retrospective Cohort Study.

BackgroundIn Ethiopia, first-line antiretroviral therapy failure is growing rapidly. However, unlike first-line therapy, to date, very little is known about the outcomes of second-line therapy. Thus, this study assessed the rate of viral re-suppression and attrition to care and their predictors among people living with HIV on second-line therapy.MethodsA retrospective cohort study was conducted on 642 people living with HIV at Dessie Comprehensive Specialized Hospital from October 2016 to November 2019. A proportional Cox regression model was computed to explore predictors of viral re-suppression (viral load less than 1000 copies/mL) and attrition to care.ResultsOut of 642 subjects, 19 (3%), 44 (6.9%), 70 (10.9%), and 509 (79.3%) patients were lost to follow up, died, transferred out, and alive on care, respectively. Similarly, 82.39% (95% CI: 79.24–85.16%) of patients had achieved viral re-suppression, with 96 per 100 person-year rate of re-suppression. Patients who switched timely to second-line therapy were at a higher rate of viral re-suppression than delayed patients [adjusted hazard rate, AHR = 1.43 (95% CI: 1.17–1.74)]. Not having drug substitution history [AHR = 1.25 (95% CI: 1.02–1.52)] was positively associated with viral re-suppression. In contrast, being on anti-TB treatment [AHR = 0.67 (95% CI: 0.49–0.91)] had lower likelihood with viral re-suppression. In the current study, attrition to care was 11% (95% CI: 8.7–13.9%). Ambulatory or bedridden patients were more at risk of attrition to care as compared with workable patients [AHR = 2.61 (95% CI: 1.40–4.87)]. Similarly, being not virally re-suppressed [AHR = 6.87 (95% CI: 3.86–12.23)] and CD4 count ≤450 cells/mm3 [AHR = 2.61 (95% CI: 1.40–4.87)] were also positively associated with attrition to care.ConclusionA significant number of patients failed to achieve viral re-suppression and attrition from care. Most identified factors related to patient monitoring. Hence, patient-centered intervention should be strengthened, besides treatment switch.

The association between effectiveness of first-line treatment and second-line treatment in gastro-oesophageal cancer

BackgroundPopulation-based predictive factors for the effectiveness of second-line palliative systemic therapy in gastro-oesophageal cancer are not available. This study investigates the predictive value of effectiveness of first-line treatment for second-line treatment outcomes in gastro-oesophageal cancer in a real-world setting. MethodsPatients with metastatic gastro-oesophageal cancer diagnosed in 2010–2017 who were treated with second-line therapy after disease progression on first-line therapy were identified from the Netherlands Cancer Registry. Patients were divided into four groups as per duration of time to treatment failure (TTF) of the first line (0–3, 3–6, 6–9 and >9 months), and the association with overall survival (OS) and second-line TTF was assessed using Kaplan-Meier curves and two-sided multivariable regression models. ResultsMedian OS since the start of the second line of patients (n = 611) with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 4.0, 4.1, 5.5 and 7.1 months, respectively (P < 0.001). Median second-line TTF of patients with first-line TTF of 0–3, 3–6, 6–9 and >9 months was 2.8, 2.4, 3.0 and 4.5 months, respectively (P < 0.001). Patients with first-line TTF of >9 months showed a longer OS than patients with first-line TTF of 0–3 months (adjusted hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.46–2.47), 3–6 months (adjusted HR 1.88; 95% CI 1.47–2.39) and 6–9 months (adjusted HR 1.31; 95% CI 1.04–1.65). Results for second-line TTF were similar. ConclusionsThis study shows a positive correlation between effectiveness of first-line therapy and outcomes of second-line therapy in gastro-oesophageal cancer. Physicians should take duration of the first line into account when considering second-line palliative systemic therapy.

Prospective Outcomes of Second Line Therapy in Acute Gvhd: Six Month Freedom from Treatment Failure and Day 28 Response in a Multicentre Study

IntroductionAcute graft-versus-host disease (aGVHD) is a significant cause of mortality post allogeneic stem cell transplantation (SCT). First line therapy is corticosteroid based for patients with aGVHD ≥grade (Gd) II. Steroid refractory (SR) aGVHD is associated with a dismal prognosis. Although experimental therapeutics is an unmet need, there is no recent prospective real world data to establish a benchmark for outcomes of best available therapy. We undertook a prospective observational multi-centre international clinical trial of outcomes of second line therapy of steroid refractory aGVHD. The aim was to measure recently defined endpoints including Day 28 (D28) overall response rate (ORR), and 6 month freedom from treatment failure (6mFFTF; defined as a patient (pt) being alive, without relapse of underlying disease or addition of new systemic therapy for aGVHD, prior to the development of chronic(c) GVHD.MethodsData was collected prospectively in a longitudinal observational study in patients starting second line therapy for SR aGVHD. Twelve UK and 2 US sites participated. Adult pts with Gd II-IV aGVHD refractory to corticosteroids were enrolled within 5 days of starting second line therapy. Modified Glucksberg criteria were used to grade aGVHD. Expert panel consensus recommendations (Martin et al 2009) were used for complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) and progressive disease (PD). Kaplan-Meier survival curves and log rank tests for comparison were done on Prism7.ResultsBetween 2014-2018, 64pts were enrolled; 4pts were excluded due to incomplete data. Baseline characteristics of the cohort are outlined in Table 1. GVHD prophylaxis varied according to centre. Forty-seven percent had T depletion; 32% ATG and 25% Alemtuzumab. GVHD was donor lymphocyte infusion (DLI) induced in 7%.At start of second line therapy,5% had Gd I, 27% Gd II and 68% Gd III-IV aGVHD. All patients had received corticosteroids at a minimum dose of 1mg/kg. Second line therapies varied, 60% received ECP and 40% non-ECP therapy including anti-TNF-alpha antibodies (20%), mycophenolate mofetil (MMF) (8%), mesenchymal stem cells (4%) and ‘other’ (8%).The cumulative incidence of 6mFFTF was 32% (n=19), with 68% (n=41) failing to meet the 6mFFTF endpoint. The causes of failure were, addition of third line therapy in 40% (n=24), relapse 8%(n=5), cGVHD 7% (n=4) and death 13% (n=8). The 6m incidence of death was 45% (n=27); death due to GVHD 30%, infection 8% and relapse 7%. D28 responses were: 56% ORR (8% CR, 28% VGPR, 20% PR), 13% SD, 18% PD and 13% died before D28. Using Kaplan-Meier analysis, median OS was 7.3m with a median follow up of 1 year. The overall cumulative incidence of death was 63% (n=38); GVHD was the leading cause of death 40%, infection 8% and relapse 8%. D28 ORR was associated with a significantly improved median OS not reached versus (vs) 5.2m (p=0.03) in pts who had SD or PD at D28. In pts that achieved 6mFFTF, median survival beyond 6m was not yet reached vs median survival of 3.9m in those that did not achieve 6mFFTF (p=0.0004). The trend was for a longer median OS of 8.2m in the ECP arm vs 5.3m in non ECP (p=0.79). GVHD Gd at start of second line therapy was associated with a longer median survival, not reached in Gd II cohort vs 5.7m in Gd III-IV cohort (p=0.25).DiscussionOur multi-centre prospective study illustrates ‘real-life’ data of clinical outcomes in pts starting second line therapy for SR aGVHD. Median survival from start of second line therapy was 7.3m with a high mortality rate of 63%. D28 ORR was 56% but only 32% met the composite 6mFFTF endpoint, although both outcomes predicted survival. The leading cause for failure of 6mFFTF was starting third line therapy which may be subject to clinician bias, however the 6m mortality was 45%, thus pts went on to die after failing for another cause. This data can be used as a contemporary data while planning studies of experimental intervention vs. best available therapy. [Display omitted] DisclosuresRadia:Mallinckrodt: Research Funding. Alfred:Mallinckrodt: Speakers Bureau. Dignan:Mallinckrodt: Research Funding, Speakers Bureau. Jagasia:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

Outcomes of Relapsed and Refractory Primary Mediastinal (Thymic) Large B Cell Lymphoma Treated with Second-Line Therapy and Intent to Transplant

Primary mediastinal (thymic) large B cell lymphoma is a subtype of diffuse large B cell lymphoma with distinct clinical, molecular, and genetic features, many of which overlap with Hodgkin lymphoma. Increasingly, initial therapy for these patients has used dose-dense chemotherapy with or without radiation with excellent results. In patients with relapsed and primary refractory disease, outcomes of second-line therapy followed by consolidation with high-dose therapy and autologous stem cell transplantation remains largely undefined. We reviewed the outcomes of 60 transplant-eligible patients with relapsed or refractory primary mediastinal (thymic) large B cell lymphoma enrolled on sequential protocols with uniform second-line therapy with intent to consolidate with autologous stem cell transplant. The estimated 3-year overall and event-free survivals for all patients were 61% and 57%, respectively, and 68% and 65%, respectively, for patients proceeding to stem cell transplant. Multivariable analysis of risk factors before transplant revealed that an incomplete response to initial therapy, advanced Ann Arbor stage at disease progression, and failure to achieve a partial remission or better to second-line therapy to be independently associated with inferior event-free and overall survival. A risk score based on these variables was able to identify patients who are unlikely to respond to conventional second-line strategies. These results suggest that salvage chemoradiotherapy with intent of subsequent high-dose therapy and autologous stem cell transplant is successful in most patients with relapsed and refractory primary mediastinal (thymic) large B cell lymphoma. Alternative strategies are warranted for a significant subset of patients with high-risk disease who are unlikely to be cured with this strategy.

Outcomes of Second-line Therapies for Stage 3 Postpartum Hemorrhage at a Tertiary Care Center [25E

INTRODUCTION: Postpartum hemorrhage (PPH) remains a major worldwide cause of maternal morbidity and mortality. Second-line interventions including uterine tamponade, dilation and curettage, uterine artery embolization (UAE), compression or hemostatic sutures, or hysterectomy, are often required to manage severe PPH. Our study sought to evaluate the success rates and complications of second-line therapies used to treat stage 3 PPH, defined as an estimated blood loss of greater than 1500 mL by the California Maternal Quality Care Collaborative. METHODS: This retrospective cohort study examined all deliveries at a tertiary care center between 2007 and 2015 complicated by a stage 3 primary PPH. The timing, order, and success rates of interventions performed and the subsequent complications were evaluated. Complications examined included ICU admission, hemorrhagic shock, disseminated intravascular coagulopathy (DIC), and endometritis. RESULTS: Of 21,067 deliveries, 267 (1.26%) were complicated by stage 3 PPH. Second-line therapies were used in 116/267 (44%). The highest success rates were found with UAE (94%, n=18), compression sutures (73%, n=29) and balloon tamponade (72%, n=68). Patients undergoing dilation and curettage as an initial second-line management were most likely to require additional intervention (54%). Endometritis and DIC were the most common complications (8%). Endometritis was most common after successful treatment with compression sutures (29%). The use of multiple interventions was associated with a higher incidence of complications. CONCLUSION: For the treatment of severe PPH, the use of uterine tamponade and UAE have high success rates and low complication rates. Our results can help inform management of stage 3 PPH, as it is less standardized.

Discontinuing VEGF-targeted therapy (VEGF-TT) for progression versus toxicity impacts outcomes of second-line therapies in metastatic renal cell carcinoma (mRCC).

503 Background: A significant minority of mRCC patients prematurely discontinue first-line (1L) VEGF-TT due to toxicity. Whether clinical outcomes differ in patients receiving second line (2L) TT based on reason for discontinuation of 1L are unknown. Methods: Patients from 15 International mRCC Database Consortium (IMDC) centers who started 2L TT were included and the reason for discontinuation of 1L collected. Treatment outcomes of 2L, including response, time to treatment failure (TTF) and overall survival (OS) were assessed. Results: 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT due to progression, 208 patients (19%) due to toxicity. 50 patients (4%) who discontinue due to other reasons were excluded. The reason for discontinuation of 1L did not differ by IMDC risk group at start of 1L VEGF-TT (p=0.54) or 2L therapy (p=0.52). Median time from 1L VEGF-TT initiation to start of 2L in patients who progressed or stopped prematurely due to toxicity was 9.8 and 7.9 months, respectively. Compared to patients who stopped 1L VEGF-TT due to progression, patients who stopped due to toxicity had longer drug free interval between 1L and 2L (1.4 vs. 0.7 months; p&lt;0.001), greater clinical benefit (CR/PR/SD) in second line (68% vs. 56%; adjusted OR: 1.58 (95%CI:1.07,2.35), p=0.023) and longer OS (17.4 vs. 11.2 months; adjusted HR: 0.69 (0.56,0.84), p=0.0002) adjusted for type of therapy, time to initiation of 2L, IMDC risk group and number of metastases at 2L (Table). Conclusions: mRCC patients with VEGF TT discontinuation 1L due to toxicity have better outcomes with 2L therapy than patients who stop therapy because of progression. These findings should be taken in consideration when designing clinical trials for second-line therapies in mRCC. [Table: see text]

Outcome of Second Line Therapy for Pediatric Patients with Hodgkin Lymphoma Who Relapse Following ABVD Based Therapy.

Abstract 2691Poster Board II-667 BackgroundTreatment outcomes for patients with newly diagnosed Hodgkin lymphoma have improved significantly. This, however, means that the number of patients relapsing following modern therapy is small and the information regarding their clinical characteristics and treatment outcome is limited. MethodsClinical information for patients with HL treated on an ABVD protocol were retrospectively collected. For those patients who suffered relapse or progression, data relating to this event, the treatment received and the outcome were collected and reviewed. ResultsBetween May 1990 and December 2006 230 children (<14 years) were treated for HL at our institution. 30 patients suffered treatment failure; 21 relapses and 9 progressions (PD). The median time to failure was 1.1years (0.05–7.29 yrs); 0.58 years for patients who progressed and 1.4 years for relapsing patients. 16 patients maintained their stage at relapse, 9 relapsed at a lower stage and 5 at a higher stage. 24 patients were subsequently treated with chemotherapy alone, one with XRT alone and 4 received CMT. One patient with progressive disease did not receive any salvage therapy. Chemotherapy protocols used included APPE (n=13), COPP (n=6), ESHAP (n=2), MOPP (n=2), COPPABV (n=2), MOPPABV (n=1) and ABVD/COPP (n=1). One patient with a nodular lymphocyte predominance HL progressed as a DLBCL and was treated on a NHL protocol. 10 patients subsequently underwent SCT (9 autologous and one allogeneic). 19/29 patients achieved CR post 2nd line therapy, while 5 each had PR and PD. OS at 6 years is 65.7%. Outcome for patients with PD was significantly worse than for those who relapsed (47.6% v. 73.2%; p=0.048). There was no difference in outcome for those patients who underwent SCT compared with those who did not (63% v. 66.4%; p=NS). ConclusionA majority of pediatric patients with HL who relapse following ABVD therapy can be salvaged. Outcome for patients following chemotherapy alone was no different from those who underwent SCT; therefore the necessity for SCT needs to be evaluated based on risk stratification. Disclosures:No relevant conflicts of interest to declare.

The impact of induction chemotherapy on the outcome of second-line therapy with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer

Using data from a large phase III study of previously treated advanced non-small-cell lung cancer (NSCLC) that showed similar efficacy for pemetrexed and docetaxel, this retrospective analysis evaluates the impact of first-line chemotherapy on the outcome of second-line chemotherapy. In all, 571 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m(2) or docetaxel 75 mg/m(2) on day 1 of a 21-day cycle. Comparisons were made based on type of first-line therapy [gemcitabine + platinum (GP), taxane + platinum (TP), or other therapies (OT)], response to initial therapy, time since initial therapy, and clinical characteristics. The two second-line treatment groups were pooled for this analysis due to similar efficacy and were assumed to have no interaction with the first-line therapies. Baseline characteristics were generally balanced. By multivariate analysis, gender, stage at diagnosis, performance status (PS), and best response to first-line therapy significantly influenced overall survival (OS). Additional factors by univariate analysis, histology, and time elapsed from first- to second-line therapy significantly influenced OS. Future trials in the second-line setting should stratify patients by gender, stage at diagnosis, PS, and best response to first-line therapy.

PD-068 An exploratory analysis of a phase III study in patients with advanced non-small cell lung cancer (NSCLC): The impact of first-line gemcitabine and platinum therapy on the outcome of second-line therapy with pemetrexed or docetaxel

PD-068 An exploratory analysis of a phase III study in patients with advanced non-small cell lung cancer (NSCLC): The impact of first-line gemcitabine and platinum therapy on the outcome of second-line therapy with pemetrexed or docetaxel