Median Duration Of Remission Research Articles

Reduced intensity allogeneic stem cell transplantation for follicular lymphoma relapsing after an autologous transplant achieves durable long-term disease control: an analysis from the Lymphoma Working Party of the EBMT

Patients with follicular lymphoma (FL) relapsing after an autologous transplant (autoSCT) may be treated with a variety of therapies, including a reduced intensity allogeneic transplant (RICalloSCT). We conducted a retrospective analysis of a large cohort of patients undergoing RICalloSCT for FL in this setting. A total of 183 patients, median age 45 years (range 21-69), had undergone an autoSCT at a median of 30 months before the RICalloSCT. Before the RICalloSCT, they had received a median of four lines (range 3-10) of therapy and 81% of patients had chemosensitive disease and 16% had chemoresistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%). With a median follow-up of 59 months, the non-relapse mortality (NRM) was 27% at 2 years. The median remission duration post-autoSCT and RICalloSCT was 14 and 43 months, respectively. The 5-year relapse/progression rate, progression-free survival and overall survival were 16%, 48% and 51%, respectively, and were associated with age and disease status at RICalloSCT. These data suggest that an RICalloSCT is an effective salvage strategy in patients with FL recurring after a prior autoSCT and might overcome the poor prognostic impact of early relapse after autoSCT.

Efficacy and safety of inotuzumab ozogamicin (InO) in older patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) enrolled in the phase 3 INO-VATE trial.

7029Background: InO, an anti-CD22 antibody-calicheamicin conjugate, has demonstrated superior response vs standard care for R/R ALL in the phase 3 INO-VATE trial (complete remission [CR]/CR with incomplete hematologic recovery [CRi], 81% [95% CI; 72–88]; minimal residual disease [MRD] negativity in responders, 78% [68–87]; median remission duration [DoR], 4.6 [3.9–5.4] mo). Herein, the efficacy and safety of InO in patients (pts) aged ≥55 vs <55 y are assessed. Methods: Per protocol, the intent-to-treat analyses of CR/CRi included the first 218 of 326 pts randomized (ITT218). The safety population included 139 pts who received ≥1 InO dose (max 1.8 mg/m2/cycle [0.8 mg/m2 on d1; 0.5 mg/m2on d8 and 15 of a 21–28 d cycle for ≤6 cycles]). MRD negativity was assessed by central flow cytometry (<0.01%). Data as of October 2, 2014 are presented (trial ongoing). Results: 109 pts in the ITT218 received InO (median age, 47 [range, 18–78] y; pts ≥55 y, 43 [39%]). Remission rates and DoR were similar whereas MRD-negat...

276. Long-Term Relapse-Free Survival of Patients with Acute Myeloid Leukemia (AML) Receiving a Telomerase-Engineered Dendritic Cell Immunotherapy

There are few treatment options for patients with intermediate and high risk AML, and remission and relapse rates are dismal especially in patients ≥60 years old. A Phase 2 clinical trial was conducted in subjects with AML to assess a dendritic cell immunotherapy (AST-VAC1) engineered to express a modified form of telomerase that is processed through both the MHC Class I and II antigen presentation pathways. AST-VAC1 was prepared from leukapheresis collections from 33 subjects and were transfected with an mRNA encoding near full length telomerase (hTERT) modified with a lysosomal sorting signal, LAMP-1, which enhances presentation to both CD4+ helper and CD8+ cytotoxic T cells. hTERT is essential for maintaining the extended proliferative lifespan of tumor cells. AML patients were enrolled if they were in complete remission (CR1 or CR2) with intermediate or high risk cytogenetics. AST-VAC1 was prepared after induction therapy and before or after completion of consolidation cycles. AST-VAC1 containing 1 × 107 cells was administered as 6 weekly followed by 6 biweekly intradermal injections. If AST-VAC1 doses were available, patients were eligible to receive additional monthly boosts. Twenty one patients (median age: 55) in complete remission (16 CR1 and 3 CR2) or early relapse (2) received at least 3 injections of AST-VAC1. Only one Grade 3 or 4 adverse event, (idiopathic thrombocytopenia), possibly related to the immunotherapy was observed. The majority of adverse events were transient including headache, fatigue, erythema and rash. The two patients who were vaccinated during early relapse progressed rapidly and did not receive the full dosing regimen of AST-VAC1. Of the 19 patients that were in CR, 13 received all 12 doses of AST-VAC1. Fifty-eight percent (11/19) developed T cell immune responses to hTERT as assessed by ELISpot analysis. Eleven of 19 patients (median follow-up 52 mos.) were in remission as of last follow-up; seven developed detectable cellular immune responses to hTERT. Of the 19 CR patients, 7 were ≥ 60 years old at the time of AST-VAC1 immunotherapy. Four of 7 patients ≥ 60 years old remained relapse free 52-59 months post AST-VAC1 immunotherapy with all four developing immune responses to hTERT. The three patients that received AST-VAC1 while in CR2 were in remission as of their last follow-up of 24, 50 and 59 months with two having hTERT immune responses. The median duration of complete remission was greater than that observed in historical controls especially for patients ≥ 60 years old where relapse-free survival at 4 years is typically 5-20%. The results suggest that immunotherapy with AST-VAC1 is safe, can stimulate immune responses to telomerase, and may extend relapse-free survival even in patients with high risk AML.

Long-Term Outcomes after Blinatumomab Treatment: Follow-up of a Phase 2 Study in Patients (Pts) with Minimal Residual Disease (MRD) Positive B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Long-Term Outcomes after Blinatumomab Treatment: Follow-up of a Phase 2 Study in Patients (Pts) with Minimal Residual Disease (MRD) Positive B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Response to Rituximab Induction Is a Predictive Biomarker in Post-Transplant Lymphoproliferative Disorder (PTLD) and Allows Successful Treatment Stratification in an International Phase II Trial Including 152 Patients

Response to Rituximab Induction Is a Predictive Biomarker in Post-Transplant Lymphoproliferative Disorder (PTLD) and Allows Successful Treatment Stratification in an International Phase II Trial Including 152 Patients

The Prognostic Value of Minimal Residual Disease (MRD) after Salvage Therapy in Patients (Pts) with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL)

Introduction: MRD positivity after induction/consolidation therapy in pts with de novo ALL has been shown to carry a very negative impact on outcome. However, the significance of MRD status in the salvage setting has not been extensively studied.Methods: We evaluated 130 pts with R/R B-cell ALL pts who received first (n=68), or second (n=62), salvage therapy between 2010 and 2015. Salvage therapies included single agent inotuzumab ozogamicin (INO; n=75), blinatumomab (n=20), or INO in combination with mini-hyper-CVD (n=35) [Jabbour E et al; EHA 2015]. Of the 130 pts treated, 78 (60%) responded and were assessed for MRD by six-color flow cytometry on marrow samples with a sensitivity of 0.01%. Morphologic responses were defined as follows, complete response (CR); disappearance of all disease with neutrophils ≥ 1.0 X 109/L, platelet > 100 X 109/L and blasts ≤ 5%, CRp; CR without platelet recovery, CRi; CR without platelet and/or neutrophil recovery.Results: The clinical characteristics of the 78 responding pts with R/R ALL are summarized in Table 1. Overall, MRD negativity was achieved at response in 41 pts (53%). Among the 41 pts who responded to single agent INO (12 CR, 26 CRp, 3CRi), 17 (41%) achieved a negative MRD status. Among the 11 pts who responded to blinatumomab (9 CR, 2Cri), 8 (73%) achieved a negative MRD status. Among the 26 pts who responded to INO in combination with mini-HCVD (21 CR, 4 CRp, 1CRi), 16 (62%) achieved a negative MRD status. Forty-four pts received allogeneic stem cell transplantation (ASCT): of those, 21 pts were MRD negative and 23 pts were MRD positive at the time of response. Median follow-up was 19 months (2-55). Overall, there was a trend for more durable morphologic responses in MRD negative pts compared with MRD positive pts: the median complete remission durations (CRD) were 17 months and 8 months, with a 2-year CRD rate of 47% and 28% respectively (Table 2). The median event-free survival (EFS) was 12 and 6 months, respectively; the 2-year EFS rates were 32% and 8%, respectively. Similarly, there was a trend for better overall survival (OS) with a median of 17 months and 9 months for pts with negative and positive MRD, respectively; the 2-year OS rates were 36% and 27%, respectively. No difference in outcome was reported whether pts were censored or not at the time of ASCT.Conclusion: In pts with R/R ALL, the achievement of negative MRD in addition to the morphologic response confers an improvement, although not statistically significant, in response duration and survival. Larger number of pts with longer follow-up is needed to validate these findings. Table 1Clinical Characteristics of Pts (n=78)N (%)/Median [range]Age (years)38 [18-87]Sex (Male)50 (64)Performance Status1 [1-3]WBC (x 109/L)3 [0.3-38]% PB Blasts0 [0-83]% BM Blasts60 [8-97]CytogeneticsDiploid20 (26)t(9;22)4 (5)t(4;11)7 (9)Miscellaneous39 (50)Not done/ Insufficient metaphases8 (10)SalvageInotuzumab Ozogamicin41 (53)Blinatumomab11 (14)Inotuzumab Ozogamicin + mini-HCVD26 (33)Number of prior therapies1 prior therapy46 (59)2 prior therapies32 (41)Table 2Response Rates and Survival by MRD StatusMRD Negative (n=41)MRD Positive (n=37)pCR2418n/aCRp1614n/aCRi15n/aCRD, median (m)1780.632-year CRD rate (%)4728EFS, median (m)1260.062-year EFS rate (%)328OS, median (m)1790.182-year OS rate (%)3627 DisclosuresCortes:Teva: Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. DiNardo:Novartis: Research Funding.

Probability of remaining in unsustained complete remission after steroid therapy withdrawal in patients with primary warm-antibody reactive autoimmune hemolytic anemia.

Primary warm autoimmune hemolytic anemia (WAIHA) is a rare autoimmune disorder frequently responding to corticosteroid first-line treatment and effective second-line treatment options such as splenectomy or anti-CD20 antibody therapy. Disease management is frequently hampered by a lack of evidence. We have investigated the probability of sustained treatment-free remission after steroid induction to facilitate clinical decision making regarding timing and necessity of second-line treatments. Response data from 31 patients with primary WAIHA initially treated with steroids were retrospectively analyzed. All patients responded by achieving a hemoglobin of at least 10mg/dl. After steroid tapering and final withdrawal, 9 of 30 patients remained in unsustained complete remission (CR). The probability of remaining in CR after steroid treatment only was 38.2 % (2 SD 20.6 %) at 15 months. The median remission duration was 100 + months with a range of 12 + to 163 + months. Of note, none of the remaining patients still on steroids achieved CR beyond 15 + months. These data indicate that a considerable proportion of patients do not need further treatment and that relapses will not occur after 15 months in CR.

Resultados del tratamiento del linfoma de células del manto con varios regímenes de inmunoquimioterapia: estudio retrospectivo

ObjectiveTo describe the clinical features and the treatment results achieved with the initial therapy among patients with mantle cell lymphoma treated at the National Cancer Institute (INC) between 2007 and 2011. MethodsDescriptive study, based on secondary institutional sources. ResultsA total of 41 patients were included, with a mean age of 60.5 years (Standard deviation SD±10.5) and a good functional status. Most of them had advanced disease at initial presentation (85%). Bone marrow involvement and extra-nodal disease were frequent, as they were seen in 73% and 39% of the patients, respectively. Histopathological diagnosis of the malignancy was mainly made on lymph node tissue (56%). First line chemotherapy regimens used with an increased frequency were R CHOP and R- HyperCVAD, in 37% and 29% of the cases, respectively. After first line therapy, a complete response was achieved in 64% of the patients, median duration of the first remission was 9 months (Interquartile range IQR 0.9 - 15). Febrile neutropenia was a frequent complication, seen in 42% of the cases. Eighteen individuals received a second line of chemotherapy, with R DHAP and R HyperCVAD being the regimens most commonly administered. ConclusionsThe clinical features of the patients are similar to those described in larger series of patients with the disease described elsewhere. The rate of complete responses, as well as the duration of the first remission after chemotherapy, is inferior when compared with the results of other groups that used similar treatment regimens.

Clinical characteristics of a group of patients with multiple myeloma who had two different λ light chains by immunofixation electrophoresis: A retrospective study from a single center.

The objective of the present study was to conduct a retrospective analysis of the clinical characteristics of a group of patients with multiple myeloma (MM) who had two different immunoglobulin λ light chains as determined by immunofixation electrophoresis (IFE). A total of 26 patients with MM had two different λ light chains by IFE at diagnosis in hospital from January 2006 to June 2012. Data were collected from the medical records of these patients. The clinical characteristics, laboratory parameters, responses, risk factors and outcomes of this special group of patients were retrospectively analyzed. The patients with MM and two different λ light chains by IFE accounted for 5.4% (26/483) of all the patients with MM during the same period. There were 17 patients (65.4%) with renal dysfunction and 10 patients (38.5%) with extramedullary plasmacytoma (EMP) at diagnosis. Ten patients (38.5%) had abnormalities by fluorescence in situ hybridization (FISH) including t(4;14), t(14;16) and/or del17p. Of these patients, three (11.5%) achieved complete remission (CR), six (23.1%) very good partial remission (VGPR), six (23.1%) partial remission (PR) and the overall remission (OR) rate was 57.7% (15/26). The OR rate of the patients who received chemotherapy with bortezomib was superior to that of the patients who received chemotherapy without bortezomib (78.6% vs. 33.3%; P<0.05). The OR rate of the patients who received autologous stem cell transplantation (SCT) was superior to that of the patients who did not receive autologous SCT (77.8% vs. 47.1%; P<0.05). The median overall survival (OS) was 12.6 months (range, 2-38 months) in this study. The patients who received chemotherapy with bortezomib had a significantly longer median OS as compared with the patients who received chemotherapy without bortezomib (19 vs. 6 months; P=0.049). The patients who received autologous SCT also had significantly longer median OS as compared with the patients who did not receive autologous SCT (18 vs. 7 months; P=0.041). The median duration of remission (DOR) was 5 months (range, 0-28 months). The patients who received bortezomib or autologous SCT had significantly longer median DOR than those who did not (P=0.046 and P=0.012, respectively). The patients with abnormalities by FISH had similar OR rates, median OS and median DOR as compared with the patients without abnormalities by FISH and there was no statistically significant difference in OR rate, median OS and median DOR between the patients with EMP and those without. The MM patients with two different λ light chains by IFE may have specific characteristics, and are accompanied by a high incidence of renal dysfunction and EMP. They have a poor prognosis and require novel therapy including bortezomib and autologous SCT.

Long-term therapeutic effectiveness of maintenance enteral nutrition for Crohn's disease.

Long-term effectiveness of enteral nutrition for maintaining remission in pediatric Crohn's disease (CD) is poorly documented. The aim of this study was therefore to examine the long-term effectiveness of enteral nutrition with aminosalicylates as maintenance therapy for those in whom remission was primarily induced by total parenteral nutrition or exclusive enteral nutrition with aminosalicylates. We retrospectively analyzed data for 58 pediatric patients with newly diagnosed CD during a median follow-up period of 50 months (range, 12-216 months). Data for remission-induced patients in whom enteral nutrition with aminosalicylates was used as maintenance therapy were analyzed with particular reference to time to first relapse and time to first intestinal surgery. Twenty-five (43.1%) of the patients relapsed with a median duration of remission of 32.4 months (range, 6-73.2 months). The cumulative rates of continuous remission were 0.88 (95%CI: 0.79-0.96) at 1 year, 0.73 (95%CI: 0.61-0.85) at 2 years, and 0.52 (95%CI: 0.35-0.68) at 5 years. None of the patients received corticosteroids, immunomodulators or anti-tumor necrosis factor agents until relapse. Disease location had no impact on timing of relapse, but with regard to disease behavior there was a trend towards earlier relapse in patients with penetrating type. Only six of the 58 patients (10.3%) needed intestinal surgery. There was a trend towards need for surgery in patients with ileal disease and with stricturing type. Enteral nutrition therapy with aminosalicylates is effective for maintaining remission and decreasing the rate of intestinal surgery in pediatric CD.

Evaluation of Cardiotoxicity by Tissue Doppler Imaging in Childhood Leukemia Survivors Treated with Low-Dose Anthracycline

Improvement in long-term survival in patients with acute childhood leukemia has led to the need for monitorization of chemotherapy-related morbidity and mortality. This study included 60 patients with acute lymphoblastic leukemia that were in remission for at least 2 years and 30 healthy controls. Systolic and diastolic function of myocardium was evaluated using conventional echocardiography and tissue Doppler imaging of the left ventricle, interventricular septum and right ventricle. Median age of patients was 11.7 years (range 10-14.9 years), and the median duration of remission was 4 years (range 2.5-5 years). All patients were treated with a low cumulative dose of adriamycin (100 mg/m(2)) according to the St. Jude Total-XIIIA protocol. The ejection fraction (EF) and fractional shortening were normal in the patient and control groups, even though EF values were significantly lower in the patients (69.5 ± 2.3 vs. 72.7 ± 3 %, P < 0.01). Myocardial systole (S m), early diastole (E m) and late diastole (A m) velocities in all segments of the myocardium were significantly lower in the patient group (P < 0.01 for all segments). Cardiotoxicity was noted in all segments of the myocardium in the patient group, despite the fact that they were all treated with a low cumulative dose of adriamycin. Based on these findings, we think that there is no safe dose for anthracyclines and periodic echocardiographic evaluation of both the left and right ventricles must be performed in all patients treated with anthracyclines, even at low doses.

Second Cord Blood Transplantation for Relapsed Myeloid Malignancies Following Allogeneic Transplantation – a Single Institute Analysis for 85 Recipients

<Introduction>Relapse after allogeneic stem cell transplantation (Allo-SCT) remains a serious concern and its prognosis is poor. Although 2nd Allo-SCT is the only curative strategy for relapsed patients after Allo-SCT, it is not easy to proceed to 2nd Allo-SCT because of the next donor availability, tumor cell control, and infectious and organ complications. Cord blood (CB) is rapidly available in Japan, but its clinical efficacy is not clearly clarified yet.<Methods>We retrospectively analyzed the outcome of 85 consecutive 2nd CB recipients with relapsed myeloid malignancies following allogeneic transplantation at Toranomon hospital between January 2005 and March 2014.<Results>Their median age was 52 years (range, 19-71). Donors at 1st Allo-SCT were related peripheral blood /bone marrow (BM) (n=24), unrelated BM (27) or CB (34), respectively. Underlying diseases were AML in 79, CML in 4, MDS in 1 and MPD in 1. The median duration of remission after 1st Allo-SCT was 197 (29-2586) days, and the median time from relapse to 2nd CBT and from 1st Allo-SCT to 2nd CBT were 85 (13-1667) days and 370 (56-2680) days, respectively. Twenty-three (27%) received re-induction chemotherapy after relapse after 1st Allo-SCT, whereas 42 (71%) received less intensive chemotherapy (low dose Ara-C and/or hydroxyurea (n=37), gemtuzumab ozogamicin (9), 5-azacitidine (2), and DLI (8)), and 20 (24%) did not receive any treatment. All except 5 patients (94%) were not in remission and 15 (18%) had active infections at the start of conditioning regimen of 2nd CBT. Performance status (PS) at 2nd CBT were 0 in 8 patients, 1 in 30, 2 in 29 and 3 in 7. Thirty-eight patients (45%) were conditioned with myeloablative regimens, whereas 47 patients received reduced-intensity. Calcineurin inhibitor (CI) plus mycophenolate mofetil were used in 36 cases (42%) as GVHD prophylaxis, while CI alone in 49 (58%). All patients received single CB unit with 2.84 (1.85-5.87) x 107/kg median number of total nucleated cell. Sixty-three patients achieved neutrophil recovery on median of 18 (11-39) days post-transplant with a cumulative incidence of 74.1%, and, among 22 who failed to achieve neutrophil recovery, 15 died before engraftment, 4 had early disease progression and 3 were rejected. Fifty-five patient (68%) developed infectious complications due to bacteria (n=42), virus (3), fungus (2) and unknown pathogens (8) within 30 days after 2nd CBT at median of 5 days post-transplant (range, -7 - 21). Median observation period of survivors was 734 (101-3023) days post-transplant. Cumulative incidences of NRM at 100 days and 2 years were 43.5% and 53.6%, respectively. Causes of NRM were Infections (n=19), idiopathic pneumonia syndrome (7), MOF+infections (4), VOD (2), GVHD (2), graft failure (1), and others (11). Higher age, myeloablative-conditioning at 1st Allo-SCT and active infection at 2nd CBT were negatively affected NRM in multivariate analysis. Twenty-seven patients relapsed at a median of 209 (16-2597) days. Cumulative incidences of relapse at 100 days and 2 years were 11.2% and 32.4%, respectively. Overall survival (OS) and progression free survival (PFS) at 2 years were 14.4% and 10.5%, respectively (Figure). Reduced-intensity conditioning at 1st Allo-SCT, younger age (<50), CI alone for GVHD prophylaxis, better PS (0-1) and absence of active infection at 2nd CBT showed a superior survival rate in multivariate analysis. Based on the results of these risk factor analysis, a group of patients who were in younger age (<50) with better PS (<2) (n=29) showed better OS (33.4%) and PFS (23.8%) at 2 years post-transplant (Figure).<Conclusion>Although CBT has provided more opportunities of 2nd transplant for relapsed patients, high NRM was noted in this study, resulted in unsatisfactory survival. Multiple factors associated with poor outcome were identified, mostly related to patients’ poor background conditions that are not easy to be ameliorated. There were, however, certain population of patients (age<50 and PS 0-1) who showed higher overall survival. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic Factors for Outcome in Patients (pts) with Refractory and Relapsed Acute Lymphocytic Leukemia (ALL) Treated with Inotuzumab Ozogamicin (IO), a CD22 Monoclonal Antibody

Background:IO was found to be highly active in pts with refractory-relapsed ALL, with an overall response rate of 58% and a median survival of 6.3 months (mos). Identifying factors associated with different outcomes on IO therapy may help select patients for this treatment and advice of prognosis.Methods:A total of 89 pts treated with IO on previous studies were analyzed. IO was given at 1.3-1.8 mg/m2 IV x 1 every 3-4 weeks or weekly (0.8 mg/m2 Day 1, 0.5 mg/m2 Days 8 and 15) every 3-4 weeks. Pretreatment factors associated with achieving marrow complete response (CR) and with survival were analyzed using standard statistical methods.Results:Baseline characteristics of the 89 pts are summarized in Table 1. Overall, 17 pts (19%) achieved CR, 29 (33%) had CRp, and 6 pts (7%) had bone marrow CR with incomplete recovery (Cri). 5 pts (6%) died within 4 weeks of starting therapy. The ORR was 58%. The rate of cytogenetic CR by morphologic responses was as follows: 8 cytogenetic CR/10 morphologic CR (80%); 16 cytogenetic CR/22 morphologic CRp (73%); and 4 cytogenetic CR/4 morphologic CRi (100%). The median survival of patients with at least marrow CR was 9 mos versus 3.4 mos for those without marrow CR (p<0.001). By multivariate analysis, a high peripheral blood absolute blast count (ABC) and low platelet count were independently associated with a lower likelihood of achieving at least marrow CR. With a median follow-up of 23 mos, (5-44), the median overall survival of pts who received IO was 6 mos; the median survival was 5 mos with the single-dose schedule and 9.5 mos with the weekly schedule. The median remission duration was 12 mos (1-year rate, 48%) (Figure 1A). Baseline characteristics independently associated with worse survival included adverse cytogenetics [complex karyotype, translocation (4;11), translocation (9;22), abnormal chromosome 17], disease beyond first salvage, and high peripheral blood ABC. Pts with 0, 1-2 or 3 adverse factors had a median survival of 42+, 7.5, and 2.4 mos, respectively (Figure 1B). To assess the benefit of achieving a marrow CR, we repeated the multivariate survival analysis using a 6-week landmark that excluded 5 pts who died within 6 weeks. The median survival was 9.2 mos and 3.4 mos for patients with and without marrow CR (p<0.001). The multivariate analysis selected the achievement of response as independently associated with survival improvement [HR=0.5 (95% CI=0.28-0.89); p=0.02]. Disease with complex karyotype, translocation (4;11), translocation (9;22), and abnormal chromosome 17 [HR=2.9 (95% CI=1.29-6.62); p=0.009], and disease status beyond first Salvage regimen [HR=1.2 (95% CI=2.16-3.91); p=0.01] were independently associated with significant worse survival. Pts with 0, 1- 2 or 3 adverse factors had a median survival of 42+, 8, and 3 mos, respectively (Figure 1C).Conclusion:Our current analyses identified a subset of adult pts with ALL in whom outcome of therapy with IO can be differentially predicted.Table 1Patients’ characteristicsN (%)ParameterSingle-Dose, n=49Weekly, n=40Overall, n=89Age, year≤183 (6)3 (8)6 (7)≥6012 (24)13 (33)25 (28)ECOG, PS0-144 (90)36 (90)80 (90)≥25 (10)4 (10)9 (10)Salvage StatusS113 (27)16 (40)29 (33)>S136 (73)24 (60)60 (67)PB ABC, x 109/L<1.033 (67)25 (63)58 (65)≥1.016 (33)15 (38)31 (35)WBC, x 109/L<4.028 (57)17 (43)45 (51)4-1111 (22)16 (40)27 (30)>1110 (20)7 (18)17 (19)BM blasts, %<203 (6)8 (20)11 (12)20-4910 (20)8 (20)18 (20)50-698 (16)6 (15)14 (16)≥7028 (57)18 (45)46 (52)Platelets, x 109/L<10043 (88)28 (70)71 (80)≥1006 (12)12 (30)18 (20)KaryotypeDiploid8 (16)9 (23)17 (19)Ph-positive9 (18)8 (20)17 (19)Translocation (4;11)6 (12)3 (8)9 (10)Complex13 (27)11 (28)24 (27)Abnormal chromosome 176 (12)5 (13)11 (12)Other6 (12)4 (10)10 (11)Prior ASCT7 (14)2 (5)9 (10)Prior HCVAD regimen35 (71)32 (80)67 (75)CD22-positive, %≥9028 (57)31 (78)59 (66)70-8914 (29)7 (18)21 (24)50-697 (14)2 (5)9 (10) [Display omitted] [Display omitted] [Display omitted] DisclosuresKadia:GSK: Research Funding; ARIAD: Honoraria. Hagop:ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding.

Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy

Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy

Spontaneous remission of acute myeloid leukemia

Spontaneous remission (SR) of acute myeloid leukemia (AML) is rare. We collected all 46 reported cases of AML with SR. Fever occurred in 91.3% of cases before remission, which was largely due to pneumonia (54.5%) and bacteremia (24.2%). Pneumonia and bacteremia were significantly more common among those who achieved complete remission (CR) compared to those who achieved only a partial remission (p = 0.032). Although 88.6% of remissions were CR, the median duration of remission was only 5 months. Eight cases did not relapse during the follow-up period. The mechanism of SR in AML likely involves the stimulatory effect of systemic febrile infection on the immune system. Immediate treatment of infections and fever may contribute to the rarity of SR in AML. The results of this review improve our understanding of the important role of the immune system in countermanding AML and may provide new ideas for immunotherapy.

Salvage therapy with mitoxantrone, etoposide and cytarabine in relapsed or refractory acute lymphoblastic leukemia

The survival of patients with relapsed or refractory acute lymphoblastic leukemia (ALL) is poor. We performed a retrospective analysis of 40 patients treated with five days of mitoxantrone 8mg/m2/day, etoposide 100mg/m2/day, and cytarabine 1000mg/m2/day (MEC). The complete remission rate was 30% and median remission duration was 11.2 months. Median overall survival was 6.5 months. In univariate analysis, patients in first relapse had improved overall survival compared to ≥second relapse (p=0.02). Thirty-day mortality rate was 7.5%. In relapsed or refractory ALL, MEC demonstrated moderate activity, but did not improve survival compared to published salvage chemotherapy regimens.

Phase II Clinical Trial of Oxaliplatin and Bevacizumab in Refractory Germ Cell Tumors

Salvage chemotherapy has curative potential in germ cell tumors (GCTs). However, novel therapies are still needed for patients failing to be cured with standard salvage chemotherapy. Bevacizumab in combination with chemotherapy has clinical activity in many solid tumors. This is the first study of bevacizumab with oxaliplatin in refractory GCT patients. Patients with metastatic GCT with progressive disease after second-line or later salvage chemotherapy were eligible. Prior high-dose chemotherapy and paclitaxel and/or gemcitabine were required unless primary mediastinal nonseminomatous GCT or late relapse. Patients received oxaliplatin-85 mg/m and bevacizumab-10 mg/kg every 2 weeks for a maximum of 14 cycles. Twenty-nine patients were enrolled and evaluated. Nine patients were late relapses and 5 had primary mediastinal nonseminomatous GCT. Median number of prior chemotherapy regimens was 4. There was no grade 4 and only 1 grade 3 toxicity. Although the primary endpoint of 12 months disease-free survival was not achieved, 8 patients (27.6%) had objective response including 1 complete remission. Median duration of remission was 5 months (range, 4 to 22 mo). Oxaliplatin plus bevacizumab was well tolerated in heavily pretreated GCTs with manageable adverse events. There was modest clinical activity but only 1 patient achieved complete remission.

Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival

Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.

Efficacy of intravenous immunoglobulins in livedoid vasculopathy: Long-term follow-up of 11 patients

Evidence for the efficacy of various therapies of livedoid vasculopathy (LV) is limited. We sought to determine efficacy and tolerability of 2 g/kg of intravenous immunoglobulins (IVIG) every 4 weeks in patients with LV. This was a long-term follow-up study of 11 patients with LV treated with 2 g/kg of IVIG assessing the clinical characteristics, disease course, and quality of life. The treatment regimen led to complete remission of ulcerations and pain in 17 of 29 disease episodes (59%) after 3 cycles and in 25 of 29 episodes (86%) after 6 cycles. Two disease episodes showed remission after 7 and 8 cycles, resulting in a total number of remissions of 27 (93%). Subscore analysis showed resolution of pain in 80% after 2 IVIG cycles. Disease severity and quality of life were significantly improved after 6 cycles. Median duration of remissions was 26.7 months after initial and 7.5 months after subsequent disease episodes. This was a retrospective study that did not include the comparison of IVIG efficacy and its impact on quality of life with treatment options. In our patients with LV, high-dose IVIG led to fast and complete resolution of pain and ulcerations and to substantial improvement in quality of life.

THU0181 Short-Lasting Flares and HAQ Impairment in Rheumatoid Arthritis Patients in Remission According to the New Acr/Eular Criteria

BackgroundThe new remission criteria suggested by the ACR/EULAR study group for trials [1] are applied in the clinical practice, although they are considered rather strict [2]. Notwithstanding this criteria, patients...