Pharmacotherapy of Disseminated Histoplasmosis in Patients with AIDS

1993 ◽  
Vol 27 (12) ◽  
pp. 1510-1518 ◽  
Author(s):  
S. Diane Goodwin ◽  
Courtney V. Fletcher ◽  
Richard H. Drew
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Maintenance Therapy ◽  
Amphotericin B ◽  
Induction Therapy ◽  
Antifungal Agent ◽  
Clinical Presentation ◽  
Biomedical Literature ◽  
Aids Patients ◽  
Disseminated Histoplasmosis

OBJECTIVE: To review the pharmacotherapy of disseminated histoplasmosis (DH) in patients with AIDS. The article provides an overview of the pathophysiology, epidemiology, clinical presentation and diagnosis of this disease. Clinical trials reporting intervention with antifungal therapy are reviewed, with an emphasis on efficacy and toxicity of these agents. DATA SOURCES: A MEDLINE search from 1976 to the present was performed to identify pertinent biomedical literature, including reviews. STUDY SELECTION: All available reviews and clinical trials in AIDS patients were evaluated, as were all available case series and interventional clinical trials. DATA SYNTHESIS: DH in patients with HIV infection is an AIDS-defining opportunistic infection caused by Histoplasma capsulatum. It is most frequently observed in HIV-infected patients living in or traveling to endemic regions. The clinical presentation most often includes fever and weight loss, but may be complicated by comorbid illness such as other opportunistic infections. Diagnosis is best established by histologic examination of peripheral blood smear or bone marrow aspirate, or isolation of the organism in cultures of blood, bone marrow, and respiratory secretions. Serologic examinations may provide supportive diagnostic information. Detection of histoplasma polysaccharide antigen (HPA) in serum or urine may prove to be a promising approach for the rapid diagnosis and therapeutic monitoring of DH in AIDS patients. In contrast to immunocompetent hosts, high relapse rates are reported after therapy in AIDS patients. Therefore, initial (induction) therapy is routinely followed by long-term (maintenance) therapy to prevent relapse. Issues regarding the selection, dosage, and duration of therapy, as well as prophylaxis of patients at highest risk, still need to be addressed by controlled clinical trials. CONCLUSIONS: Amphotericin B is presently the drug of choice for induction therapy. Maintenance therapy with either amphotericin B or an oral azole antifungal agent active against H. capsulatum is necessary to prevent relapse. Itraconazole, a triazole antifungal agent, may provide effective alternative therapy for both induction and maintenance treatment of DH.

Bortezomib-Based Therapy without Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma Patients with t(4;14): A Canadian National Trial,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3982-3982
Author(s):  
Donna E. Reece ◽  
Giovanni Piza Rodriguez ◽  
David Szwajcer ◽  
Leonard A Minuk ◽  
Mariela Pantoja ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Disease Progression ◽  
Induction Therapy ◽  
Research Funding ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Newly Diagnosed

Abstract Abstract 3982 Newly diagnosed multiple myeloma (MM) patients (pts) with t(4;14) identified by FISH who undergo a single ASCT after older induction regimens have a median progression-free survival (PFS) of only 8–9 months (mos) and median overall survival (OS) of 18 mos (Chang H, et al. Bone Marrow Transplan t 2005; 36: 793; Gertz M, et al. Blood 2005; 106: 2837). Given the efficacy of bortezomib in t(4;14) disease, we designed a phase II study based on this agent in which ASCT was not performed as part of first-line therapy. Pts received induction therapy with four 21-day cycles of pegylated liposomal doxorubicin 30 mg/m2on day 4, bortezomib 1.3 mg/m2on days 1, 4, 8, 11 and dexamethasone 40 mg on days 1–4, 8–11, 15–18 of cycle 1 and on days 1–4 and 11–14 of cycles 2–4 (DBD), followed by post-induction therapy with eight 28-day cycles of oral cyclophosphamide 300 mg/m2on days 1, 8, 15, 22, bortezomib 1.5 mg/m2 on days 1,8,15 and prednisone 100 mg q 2 days (CyBor-P). Maintenance therapy with dexamethasone 40 mg/weekly was then administered until disease progression. Although elective stem cell collection was recommended after induction therapy, routine ASCT was not performed in the absence of disease progression. Between February 2008-May 2011, 383 newly diagnosed MM pts were screened for t(4;14) in 8 Canadian centers, and 43 (11.2%) were found to be positive by FISH. Five did not meet the CRAB criteria for symptomatic MM, 7 were ineligible, 3 declined participation and 28 were entered onto study. One of these was later determined to have a variant abnormality of chromosome 4, but not t(4;14), and underwent ASCT after induction therapy; this pt is included in the safety analysis only. The median age was 60 years (range 42–69) and 63% were male. The median percent of nuclei positive for t(4;14) by FISH in the initial bone marrow (unpurified) was 26% (range 2–62), serum β2-microglobulin 239 nmol/L (range 43–1695) and albumin 36 g/L (range 28–48); ten pts had ISS stage 1,10 had stage 2 and 7 had stage 3 MM. Immunoglobulin subtype included IgGκ in 7, IgAκ in 6, IgAλ in 6, IgGλ in 5 and IgMλ in 1. Using modified uniform criteria, the best response in 23 evaluable pts includes: sCR in 6 (26%), CR in 4 (17%), VGPR in 9 (39%), PR in 2 (9%) and SD in 2 (9%). Median F/U is 13.5 mos (range 1.2–35); 6 have progressed at median of 3 mos on study (range 1–11). Four pts have died (due to progression in 3 and complex medical problems/consent withdrawal in 1 in VGPR). SAEs were reported in 7 pts; only 6 pts (21%) developed grade 2 peripheral neuropathy, which necessitated dose reductions of bortezomib in 4. The actuarial 2-yr PFS is 47.7% (95%CI 25.9–87.9%), median PFS is 23. 2 months and 2-yr OS is 76.8% (95%CI 58.3–100%); the median OS has not yet been reached. We conclude: 1) the incidence of t(4;14) by FISH in newly-diagnosed MM pts is 11.2%; which appears to be lower than the 15% anticipated 2) 11.6% of these are asymptomatic; 3) this bortezomib-based regimen is well-tolerated; 4) the overall response rate (sCR + CR + VGPR + PR) is 91% with 82% achieving ≥ VGPR and 43% ≥ CR; 5) the PFS and OS with this approach compare favorably with those seen with older studies of single or double ASCT, and even with some recently reported trials using more modern induction regimens before ASCT, in pts with t(4;14); and 6) the use of more effective maintenance therapy, including agents targeting the aberrations associated with t(4;14), would be of interest in future trials. Disclosures: Reece: Millennium: Research Funding; Otsuka: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol, Meyers, Squibb: Honoraria, Research Funding; Amgen: Honoraria. Off Label Use: Bortezomib regimens other than VMP (boretzomib, melphalan and prednisone)for initial therapy of myeloma. Piza Rodriguez:Celgene: Unrestricted educational grant; Otsuka: Honoraria. Belch:Ortho/Janssen: Honoraria; Celgene: Honoraria. White:Celgene: Consultancy, Honoraria, Research Funding; Ortho/Janssen: Honoraria, Research Funding. Chen:Celgene: Research Funding. Kukreti:Celgene: Honoraria.

scholarly journals Deepening of Response after Completing Rituximab-Containing Primary Therapy in Patients with Waldenstrom Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2887-2887
Author(s):  
Jorge J. Castillo ◽  
Joshua Gustine ◽  
Toni Dubeau ◽  
Kirsten Meid ◽  
Andrew Keezer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Maintenance Therapy ◽  
Median Time ◽  
Induction Therapy ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
Hemoglobin Level ◽  
Primary Therapy ◽  
Lower Serum ◽  
Median Serum

Abstract Introduction: Rituximab-containing regimens are commonly used for primary therapy in patients with symptomatic Waldenstrom macroglobulinemia (WM), and response is defined by decrease in serum IgM levels. In previous studies, we and others observed that in certain WM patients completing rituximab-based primary therapy, serum IgM levels continued to decline following completion of therapy, deepening the response to therapy. To further clarify the frequency and clinical characteristics, we evaluated a large population of treatment naïve patients treated at our WM center with rituximab-containing regimens. Methods: Patients with a clinicopathological diagnosis of WM requiring therapy based on criteria from the 2ndInternational Workshop for WM (IWWM) who received a rituximab-containing regimen as primary therapy in the WM center at our institution from 2005 to 2016 were included. Responses were defined per criteria from the 6thIWWM. Findings were stratified based on patients having received, or not, maintenance therapy after induction therapy. We gathered pertinent clinical data, including responses at the end of induction, at the end of maintenance, and at the lowest serum IgM level after completion of induction and/or maintenance. Response deepening was defined as 25% decrease in serum IgM at any point after completion of therapy. Results: 179 patients met eligibility criteria for this study. Induction therapy consisted of bortezomib, dexamethasone and rituximab (BDR) (N=86; 48%); bendamustine and rituximab (Benda-R) (N=57; 32%); cyclophosphamide, dexamethasone and rituximab (CDR) (N=36; 20%). 117 (65%) patients received maintenance therapy. There were no differences in baseline characteristics for age, gender, serum IgM, hemoglobin level, bone marrow involvement, hemoglobin, platelet count, beta-2-microglobulin level, MYD88 and CXCR4 mutation status, time to therapy, regimen, and receipt of maintenance therapy vs. observation status. At baseline, median serum IgM levels for patients who received maintenance was 4,445 mg/dl (range 289-8,100 mg/dl) and for those who were observed was 4,400 mg/dl (range 155-10,020 mg/dl) (p=0.37). Following induction therapy, median serum IgM levels declined to 969 mg/dl (range 33-5,940 mg/dl) and 1,366 mg/dl (114-7,108 mg/dl) for patients who subsequently received maintenance or were observed (p<0.001 for each group versus baseline; p=0.11 for serum IgM comparisons post-induction between groups). Following maintenance, median serum IgM level declined to 528 mg/dl (range 10-5,410 mg/dl; p<0.001 compared to end of induction). Further declines in serum IgM post-maintenance occurred, with best post-maintenance serum IgM level of 384 mg/dl (range 9-4,759 mg/dl; p<0.001 compared with end of maintenance, with 72/117 (62%) patients experiencing a lower serum IgM level and 44/117 (38%) having at least a 25% decrease in serum IgM levels. Median time from end of maintenance to lowest IgM level was 1.6 years (0.1-7.9 years). For patients observed after induction therapy, the median best serum IgM level was 1,253 mg/dl (11-7,108 mg/dl; p=0.01 compared to end of induction), with 29/62 (47%) patients having a lower serum IgM level than at completion of induction, and 18/62 (29%) had at least a 25% decrease in serum IgM level. Median time from end of induction to lowest IgM level for those observed was 1.6 years (0.2-5.1 years). Categorical responses are shown in Figure. Importantly, when analyzing all patients, hemoglobin level <11.5 g/dl (OR 0.44, 95% CI 0.23-0.88; p=0.02), bone marrow involvement ≥50% (OR 0.49, 95% CI 0.26-0.93; p=0.03), presence of CXCR4 mutations (OR 0.33, 95% CI 0.13-0.87; p=0.03) and serum IgM level ≥4,000 mg/dl (OR 0.53, 95% CI 0.29-0.99; p=0.04) were associated with lower odds of response deepening after completing therapy. Conclusion: A third of WM patients who receive primary therapy with rituximab-containing regimens experienced deepening of response following completion of therapy, with a median time to best response of 1.6 years. High serum IgM levels and bone marrow burden, low hemoglobin levels, and presence of CXCR4 mutations at primary therapy initiation were associated with lower odds of response deepening. Figure. Figure. Disclosures Castillo: Genentech: Consultancy; Beigene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Millennium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Hunter:Pharmacyclics: Consultancy. Treon:Janssen: Consultancy, Other: Travel, Accommodations, Expenses; BMS: Research Funding; Johnson & Johnson: Consultancy; Pharmacyclics: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding.

scholarly journals Efficacy of Maintenance Therapy Following Auto-HSCT Depending on MRD Status in Patients with Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3432-3432 ◽  
Author(s):  
Maxim V. Solovev ◽  
Larisa P. Mendeleeva ◽  
Maiia V. Firsova ◽  
Irina V. Galtseva ◽  
Julia Davydova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Randomized Clinical Trials ◽  
Plasma Cells ◽  
Disease Stage ◽  
Color Flow ◽  
Receive Maintenance Therapy ◽  
To Receive

Abstract Background: The results of international randomized clinical trials emphasize the expediency of maintenance therapy following auto-HSCT. However, these studies did not assess such important issues as the need for maintenance therapy in patients who have achieved complete remission (CR) or stringent CR following auto-HSCT. Probably, the results of studying MRD following auto-HSCT will allow receiving a substantiated answer to this question. Aims: To evaluate the efficacy of maintenance therapy following auto-HSCT depending on MRD in patients with multiple myeloma. Patients and methods: Over the period from January 2012 to April 2018, 70 MM patients (24 males and 46 females) aged 32 to 65 years (median=56) were enrolled into a prospective study. The disease stage according to the International Staging System (ISS) was I, II and III in 28, 19 and 23 patients, respectively. All patients received induction therapy with bortezomib; immunomodulatory drugs were used in 10 cases. After the induction therapy, a single and tandem auto-HSCT were performed in 57 and 13 patients, respectively. On Day 100 following auto-HSCT, bone marrow examination was carried out in order to determine MRD using six-color flow cytometry with a panel of antigens: CD38, CD138, CD45, CD56, CD117, CD19. MRD-negative status was diagnosed in case of detection of <20 clonal plasma cells among 2,000,000 white blood cells (<0.001%; detection limit 10-5). On Day 100 after the auto-HSCT, all patients achieved CR of the disease and were randomized to receive maintenance therapy with lenalidomide 15 mg/day from Day 1 to Day 21 of a 28-day course within a year or no such therapy. The follow-up period since the moment of MRD determination was 2-28 months (median 15). Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10. Results: 37 patients were randomized to receive maintenance therapy with lenalidomide following auto-HSCT, including 23 patients in whom plasma cell immunophenotyping showed the lack of MRD and 14 patients in whom MRD-positive status was confirmed. Thirty-three patients were followed-up without further treatment after the auto-HSCT, including 24 cases with MRD-negative status and 9 cases with the presence of abnormal plasma cells in the bone marrow. The compared groups were comparable in respect of such parameters as age and the ISS stage. The differences between two-year PFS rates in MM patients with MRD-negative status following auto-HSCT who received (n=23) or didn't receive (n=24) the maintenance therapy, showed no statistical significance (p=0.3) and were 88% and 74%, respectively (Fig.1a). In patients with MRD-positive status following auto-HSCT who received lenalidomide, two-year PFS rate was significantly (p<0.05) higher and was 92% versus 45% in the group of patients who didn't receive the maintenance therapy (Fig.1b). Conclusion: Achievement of MRD-negative status following auto-HSCT was accompanied by high values of PFS regardless of the use or not use the maintenance therapy with lenalidomide (88% versus 74%, p=0.3). Prescription of the maintenance therapy to patients with MRD-positive status following auto-HSCT improves the PFS. Disclosures No relevant conflicts of interest to declare.

Prognosis of Acute Myeloid Leukemia with Translocation (8;21): A Survey of 142 Cases Investigated in the JALSG AML97 Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4511-4511
Author(s):  
Nahoko Hatsumi ◽  
Shuichi Miyawaki ◽  
Hisashi Sakamaki ◽  
Shigeki Ohtake ◽  
Fumiharu Yagaski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Risk Group ◽  
Standard Dose ◽  
Significant Prognostic Factor ◽  
Female Ratio ◽  
Poor Risk ◽  
Two Factors ◽  
Wbc Count

Abstract Background: Translocation (8;21) is one of the most common structural aberrations found in AMLand good response rates and a better DFS have been described in pts possessing it. Especially, the DFS rate may exceed 60–70% in younger pts given repetitive courses of HDAra-C. However, it was recently reported that a subtype of AML with t(8;21) showed a poor prognosis and this case also had the KIT mutation. As a result, we retrospectively analyzed the prognosis of AML pts with t(8;21) prospectively enrolled in the JALSG AML97 study. Patients and Methods: Between 1997 and 2001, JALSG AML97 enrolled 809 pts previously untreated for AML and pts with M3 were excluded. From the 789 eligible pts, we selected the subjects with t(8;21) for this study. Induction therapy consisted of cytarabine and idarubicin. All CR pts were randomized to receive either four courses of standard dose consolidation therapy without maintenance therapy or three courses of standard dose consolidation with 6 courses of maintenance therapy. HDAra-C was not administered in the JALSG AML97 study. Peripheral blood and bone marrow smears and karyotypes were reevaluated by the central review committees. Any patients who underwent SCT were censored at the date of SCT. The Kaplan-Meier method was used to estimate OS and DFS. For comparisons of OS or DFS, the log rank test was used. Result: Cytogenetic studies were performed in 783 patients (99.2%) and only 15 studies resulted in failure. One hundred forty-two (18.5%) of those pts showed t(8;21). The median age was 43 yrs (15–64). The male: female ratio was 95: 47. The distribution of FAB types was as follows: AMLM2, 130; M4, 6; M1, 5; and M5, 1. A total of 69 (48.6%) pts had a sole t(8;21), 46 (32.4%) had a loss of a sex chromosome, and 27 (19.0%) had other cytogenetic abnormalities. The CR rate was 90.0%. Thirty-two pts underwent two courses of induction therapy. The early death (< one month) rate was 1.4% (2/142). Only a high WBC count (>=10x109/L) was found to be a marginally significant prognostic factor (p=0.0517). The estimated OS rate at 5yrs was 53.6%, and the DFS of the CR pts was 41.2%. We found no relationship between OS or DFS and the following factors: age, gender, karyotypic abnormality, performance status, the percentage of MPO positive blasts, the presence or absence of Auer rods, the platelet count, the number of induction therapies for CR and the type of postremisson therapy. However, two factors, the WBC count and the percentage of blasts in bone marrow were found to be strongly predictive factors for the outcome. For the pts with a WBC count >=10x109/L, the DFS rate at 5yrs was 30.8%, while for the pts with less than 10x109/L, it was 48.8% (p=0.0215). For the pts with blast >=50% and less than 50%, the DFS rates at 5yrs were 32.2% and 56.7% (p=0.0087), respectively. According to these two factors, a poor risk group (N=30, 21.0%) was thus identified. They had a WBC count >=10x109/L and blast >=50%. The DFS rate at 5yrs was only 22.3 % in the poor risk group while that of the other pts was 48.9% (P=0.0003). Conclusion: This study confirmed that all AML pts with t(8;21) shows a high response rate and a good prognosis, thus indicating that this favorable AML group includes a poor risk group which can be identified based on the WBC count and the blast percent in the bone marrow.

scholarly journals The Role of 18f-FDG-PET/CT in Characterizing Depth of Response in High Risk Smoldering Multiple Myeloma Patients Treated with Carfilzomib, Lenalidomide, and Dexamethasone (KRd)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Elizabeth Hill ◽  
Neha Korde ◽  
Candis Morrison ◽  
Alexander Dew ◽  
Ashley Carpenter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Clinical Trials ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Data Monitoring ◽  
Independent Data ◽  
Genetics Research ◽  
Pet Ct

Introduction A direct association exists between minimal residual disease (MRD) negativity and prolonged survival in multiple myeloma (MM) (Landgren et al, BMT 2016). 18F-fluoro-deoxy-glucose (FDG) positron emission tomography-computed tomography (PET/CT) is a recommended monitoring technique for patients with MM as persistence of FDG uptake after induction therapy, prior to maintenance, is an independent risk factor for progression. Therefore PET/CT and MRD detection in the bone marrow are complementary prognostic tools prior to initiation of maintenance therapy. In patients with smoldering multiple myeloma (SMM), the presence of a focal FDG-avid lesion without underlying osteolytic lesion on PET/CT is associated with rapid progression to MM. However, little is known about the prognostic value of PET/CT for SMM patients receiving treatment. Herein, we show that treatment of high risk (HR)-SMM with carfilzomib, lenalidomide, and dexamethasone with lenalidomide maintenance (KRd-R) leads to sustained remissions detected on PET/CT imaging. Methods Trial design including key results for KRd-R in HR-SMM (NCT01572480) has been submitted to the meeting separately (abstract ID: 136148). As part of the study design, all eligible patients had bone marrow biopsies with multicolor flow cytometry (MRD sensitivity, 10-5) and whole-body PET/CT performed at baseline and at key time points, including achievement of complete response (CR) or completion of KRd induction (8 cycles), after 1 and 2 years of -R maintenance, and annually thereafter. PET/CTs were evaluated by nuclear medicine radiologists blinded to flow cytometry and considered positive if at least one focal hypermetabolic (above background reference) lesion and/or heterogenous bone marrow involvement were present, as defined by the IMWG (Hillengass et al. Lancet Oncol 2019). Results As of data cutoff, 46 patients had completed at least 8 cycles of therapy and had 2 sequential PET/CTs performed. By the end of induction therapy, no patient developed progressive disease and the overall response rate was 100%. Approximately 72% of patients with baseline negative PET/CTs remained negative, 11% of patients had resolution of previous focal/heterogenous FDG avidity, 15% of patients had decrease or stable focal/ heterogenous lesions, and 2% developed new focal lesions. Table 1 shows the results at subsequent time points of one and two years of maintenance therapy. Throughout this time period, one patient developed a lytic lesion after 1 year of maintenance therapy. However, 3 patients had either resolution or decrease in focal/heterogenous lesions. Specifically, after 8 cycles of combination therapy, 33 patients (70.2%, 95% CI 55.9 - 81.4%) had a response of MRD negative CR based on bone marrow flow cytometry and 26 patients (55.3%; 95% CI 41.2-68.6%) had a negative PET/CT in addition to MRD negative CR (Table 2). Conclusions It is important to evaluate the tools used in MM response assessment specifically in the SMM population as more studies report results of treatment in this population. MRD information can be used as a biomarker to evaluate the efficacy of different treatment strategies. This study demonstrates an exceptionally high rate of concordance between MRD negativity by flow cytometry and negative PET/CT after 8 cycles of KRd. However, 15% of patients were MRD negative yet had positive findings on PET/CT. While these lesions were not biopsy proven, some resolved during maintenance therapy. Further follow-up is needed to determine whether early MRD negativity in bone marrow with negative PET/CT correlates to longer overall survival and decreased progression to MM compared to those patients with a positive PET/CT. The use of PET/CT imaging may increase our understanding in assessing depth response to treatment in HR-SMM patients and be an important outcome predictor. Disclosures Korde: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other.

Receipt of Maintenance Therapy Is Most Predictive of Survival in Older Acute Lymphoblastic Leukemia Patients Treated with Intensive Induction Chemotherapy Regimens.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2600-2600
Author(s):  
Daniel J. Landsburg ◽  
Edward A. Stadtmauer ◽  
Alison W. Loren ◽  
Steven C. Goldstein ◽  
Noelle V. Frey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Small Sample ◽  
Hazard Ratio ◽  
High Dose ◽  
Cox Regression Analysis

Abstract Abstract 2600 Background: Older patients diagnosed with acute lymphoblastic leukemia (ALL) receiving intensive induction therapy often suffer from poor outcomes due to therapy-related toxicity and high rates of relapse. We previously reported that patients age ≥60 diagnosed with ALL and treated at our institution with either hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine (hyperCVAD) or daunorubicin, vincristine and prednisone (DVP) induction therapies achieved comparable rates of survival. Now with longer follow-up and further analysis, we describe additional outcomes and factors predictive of survival in this patient population. Methods: Thirty-seven patients diagnosed with ALL at age ≥60 and treated at the University of Pennsylvania between July 2003 and June 2011 who received induction therapy with either hyperCVAD (≥1 A+B cycle) or DVP (phase I+II) were analyzed. HyperCVAD was administered as first described at the MD Anderson Cancer Center and DVP per the ECOG 2993/UKALL XII protocol. Therapy adjustments and bone marrow biopsy to confirm remission were performed at the discretion of the treating physician. Almost all Philadelphia chromosome (Ph) positive patients received a tyrosine kinase inhibitor. Event-free survival (EFS) was defined as the time from diagnosis to either relapse or death from any other cause. Results: Table 1 describes baseline characteristics. Table 2 describes outcomes. If achieved, morphologic remission was recognized upon the first bone marrow assessment performed while on therapy, which occurred after a median of 4 (2 A+B) cycles of hyperCVAD and by completion of phase II induction of DVP. EFS and overall survival (OS) trended in favor of DVP. HyperCVAD patients were more likely to complete intensive therapy but less likely to receive maintenance therapy, and more likely to relapse with the majority of relapses occurring off active treatment. Primary reasons for not starting or stopping maintenance therapy were infections and cytopenias. Relapsed disease was the most frequent cause of death. Table 3 describes univariate Cox regression analysis. Receipt of maintenance therapy demonstrated the strongest association with survival (p=0.0001, hazard ratio 0.06 for EFS; p=0.0002, hazard ratio 0.05 for OS). Valid multivariate analysis could not be performed due to small sample size. Conclusions: In older ALL patients treated with aggressive induction therapies and achieving remission, receipt of maintenance therapy appears to be most predictive of EFS and OS. Outcomes in the DVP and hyperCVAD groups were similar although a trend towards prolonged survival in the DVP group was seen, which may be explained by a lower rate of relapse due to a higher likelihood of remaining on therapy over time. Our findings suggest that these patients may benefit from attenuated courses of intensive initial therapy in order to avoid developing toxicities that may prohibit tolerance of prolonged maintenance therapy. Disclosures: No relevant conflicts of interest to declare.

Outcomes of Multiple Myeloma Patients with Del 17p Undergoing Autologous Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Iuliana Vaxman ◽  
Alissa Visram ◽  
Prashant Kapoor ◽  
Abdullah S. Al Saleh ◽  
Shaji K. Kumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Advisory Board ◽  
Newly Diagnosed ◽  
Immunomodulatory Agents

Introduction High risk (HR) multiple myeloma (MM) constitutes approximately 25 % of newly diagnosed patients and is a subgroup of MM patients that is variably defined. Patients with 17p deletion are considered HR and their optimal treatment approach has not been determined. Various strategies have been suggested to improve outcomes in MM patients harboring del 17p, including tandem transplants. Recently, the long-term outcomes of the phase 3 EMN02 trial were published with the study group receiving bortezomib, cyclophosphamide and dexamethasone (VCd) induction prior to transplant. There are no data demonstrating that tandem transplant is applicable to the US population using induction containing immunomodulatory agents and bortezomib. Aim To report on outcomes of newly diagnosed MM patients with del 17p that underwent autologous stem cell transplantation (ASCT). Methods Retrospective study of all consecutive newly diagnosed MM patient with del 17p that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Patients were defined by the Mayo Medical Lab as 17p deleted and included if they met the following criteria: If 50 cells in the bone marrow sample and 10 cells with the deletion were identified (20%) or if the bone marrow sample had between 20-50 total cells and 20% cells with the deletion were identified. We excluded patients that relapsed prior to ASCT (as those patients were excluded in the EMN02 trial), patients that underwent ASCT more than 12 months from the diagnosis and patients that underwent tandem ASCT (defined as two consecutive ASCT within 180 days of each other without relapse in between). Consolidation treatment was defined as treatment given after transplant for up to six 28-day cycles and maintenance was defined as all treatment given after ASCT for more than 6 months. Combined maintenance was defined as maintenance regimens that included two novel agents. Results 116 patients with MM and 17p deletion underwent ASCT at Mayo Clinic between January 2013 and April 2020. The median age at diagnosis was 62 (IQR 57-68, range 34-76) years. Forty-five (39%) patients were over 65 years. Nine patients (8%) had triple-hit MM and 34 (29%) had double-hit MM. Median follow-up of the survivors was 33 months (IQR 21-54). Consolidation therapy was given to 36 patients (31%) and maintenance was given to 91 patients (78%). Seven patients relapsed before day 100. There was no difference in the OS (P=0.72) or PFS (P=0.1) between patients that received VRd (bortezomib, lenalidomide and dexamethasone) versus VCd (bortezomib, cyclophosphamide and dexamethasone) induction (Figure 1). When comparing patients that received proteasome inhibitors (PIs)+ immunomodulatory agents (IMiDs) as induction to patients that received VCd induction, PFS was longer for patients that received the PIs + IMiDs (HR 0.53 P=0.04, 95% CI=0.3-0.98) (Figure 2), however there was no OS difference (P=0.61). Maintenance therapy was given to 94 patients (81%). There was no OS (P=0.34) or PFS (P=0.36) difference between IMiD based and PI based maintenance, but there was a PFS advantage to patients that received two drug maintenance (HR= 0.41, P=0.037, 95% CI 0.14-0.95) (Figure 2). The median OS and PFS of the entire cohort were not reached and 29 months, respectively. Conclusions The outcomes of our patients were similar to that of the single arm ASCT in the EMN02 trial, and no difference in outcomes were found between patients that received VRd and VCd induction, suggesting that tandem transplants should be considered for 17p deleted MM patients. Dual novel agent maintenance therapy is important in improving outcome. Disclosures Kapoor: Celgene: Honoraria; GlaxoSmithKline: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Janssen: Research Funding. Kumar:Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Dr. Reddy's Laboratories: Honoraria; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Cellectar: Other; Genecentrix: Consultancy; Tenebio: Other, Research Funding; Adaptive Biotechnologies: Consultancy; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Novartis: Research Funding; Carsgen: Other, Research Funding; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; MedImmune: Research Funding. Dispenzieri:Pfizer: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Celgene: Research Funding. Dingli:Alexion: Consultancy; Sanofi-Genzyme: Consultancy; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; Millenium: Consultancy; Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Apellis: Consultancy. Gertz:DAVA oncology: Speakers Bureau; Proclara: Other; Abbvie: Other; Physicians Education Resource: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Research to Practice: Other; Ionis/Akcea: Other: personal fee; Celgene: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; Annexon: Other: personal fee; Alnylam: Other: personal fee; Prothena: Other: personal fee; Janssen: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Aurora Bio: Other; Springer Publishing: Patents & Royalties; Sanofi: Other; Amgen: Other: personal fee.

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