Azacitidine Plus Gemtuzumab Ozogamicin (GO): A Novel Combination in the Treatment of Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS) in the Elderly.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1981-1981 ◽  
Author(s):  
Sucha Nand ◽  
John Godwin ◽  
Scott Smith ◽  
Kevin Barton ◽  
Eliza Germano ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Residual Disease ◽  
The Elderly ◽  
Gemtuzumab Ozogamicin ◽  
Outpatient Setting ◽  
Grade 3 ◽  
Wbc Count ◽  
Related Mortality

Abstract AML and high-risk MDS in the elderly carry a poor prognosis. Only 46% of AML patients receiving standard chemotherapy achieve complete remission (CR) and treatment-related mortality approaches 30% above age 60. In 2005, we initiated a Phase II trial for elderly patients with newly diagnosed AML or MDS, using the following outpatient treatment schema: If white blood cell (WBC) count at presentation was >10,000/ul, pt was started on hydroxyurea 1500 mg twice daily by mouth. Leukapheresis was performed if WBC >100,000/ul. Once WBC count was <10,000/ul, the patient received azacitidine 75 mg/m2 s/cu D1–7 and GO 3 mg/m2 on D8. A bone marrow was performed on D14 and induction therapy repeated for residual disease. Those who achieved CR were given one consolidation treatment with azacitidine+GO in same doses after recovery of blood counts. A total of 13 pts have been treated to date. Eleven had AML by WHO classification and 2 MDS (both RAEB). The median age was 77 (62–83) and 7 were male. Ten patients required retreatment on D14. Ten patients (76%) achieved CR. Six patients developed grade 3 toxicities: 5 neutropenic fever and 1 typhlitis, all requiring hospitalization. There were no treatment-related deaths. Median follow up is 7 months (2–13 months) and eleven patients remain alive. Two patients have died from relapsed or refractory disease. Nine patients remain in CR with a median duration of remission of 7 months (2–13 months). The trial is ongoing with an accrual goal of 20. Our early experience with this novel combination is quite encouraging. Cytoreduction with hydroxyurea and leukapheresis followed by azacitidine and GO appears to be a safe and effective regimen for elderly patients with AML and the therapy can be given in the outpatient setting. These preliminary results need to be confirmed in a larger cohort of patients.

Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
The Elderly ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Common Sign ◽  
Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

Depth of response and minimal residual disease status in ultra high-risk multiple myeloma and plasma cell leukemia treated with daratumumab, bortezomib, lenalidomide, cyclophosphamide and dexamethasone (Dara-CVRd): Results of the UK optimum/MUKnine trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8001-8001
Author(s):  
Martin F. Kaiser ◽  
Andrew Hall ◽  
Katrina Walker ◽  
Ruth De Tute ◽  
Sadie Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Residual Disease ◽  
Cell Leukemia ◽  
Ultra High Risk ◽  
Grade 3 ◽  
Minimal Residual

8001 Background: Patients with ultra high-risk (UHiR) newly diagnosed multiple myeloma (NDMM) and patients with plasma cell leukemia (PCL) continue to have dismal outcomes and are underrepresented in clinical trials. Recently, improved responses with anti-CD38 monoclonal antibody combination therapy have been reported for NDMM patients. We report here outcomes for NDMM UHiR and PCL patients treated in the OPTIMUM/MUKnine (NCT03188172) trial with daratumumab, cyclophosphamide, bortezomib, lenalidomide, dexamethasone (Dara-CVRd) induction, augmented high-dose melphalan (HDMEL) and ASCT. With final analysis follow-up surpassed in Feb 2021, we report here early protocol defined endpoints from induction to day 100 post ASCT. Methods: Between Sep 2017 and Jul 2019, 107 patients with UHiR NDMM by central trial genetic (≥2 high risk lesions: t(4;14), t(14;16), t(14;20), gain(1q), del(1p), del(17p)) or gene expression SKY92 (SkylineDx) profiling, or with PCL (circulating plasmablasts > 20%) were included in OPTIMUM across 39 UK hospitals. Patients received up to 6 cycles of Dara-CVRd induction, HDMEL and ASCT augmented with bortezomib, followed by Dara-VR(d) consolidation for 18 cycles and Dara-R maintenance. Primary trial endpoints are minimal residual disease (MRD) status post ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. Data is complete but subject to further data cleaning prior to conference. Results: Median follow-up for the 107 patients in the safety population was 22.2 months (95% CI: 20.6 – 23.9). Two patients died during induction due to infection. Bone marrow aspirates suitable for MRD assessment by flow cytometry (10-5 sensitivity) were available for 81% of patients at end of induction and 78% at D100 post ASCT. Responses in the intention to treat population at end of induction were 94% ORR with 22% CR, 58% VGPR, 15% PR, 1% PD, 5% timepoint not reached (TNR; withdrew, became ineligible or died) and at D100 post ASCT 83% ORR with 47% CR, 32% VGPR, 5% PR, 7% PD, 10% TNR. MRD status was 41% MRDneg, 40% MRDpos and 19% not evaluable post induction and 64% MRDneg, 14% MRDpos and 22% not evaluable at D100 post ASCT. Responses at D100 post ASCT were lower in PCL with 22% CR, 22% VGPR, 22% PR, 22% PD, 12% TNR. Most frequent grade 3/4 AEs during induction were neutropenia (21%), thrombocytopenia (12%) and infection (12%). Grade 3 neuropathy rate was 3.7%. Conclusions: This is to our knowledge the first report on a trial for UHiR NDMM and PCL investigating Dara-CVRd induction and augmented ASCT. Response rates were high in this difficult-to-treat patient population, with toxicity comparable to other induction regimens. However, some early progressions highlight the need for innovative approaches to UHiR NDMM. Clinical trial information: NCT03188172.

A phase II trial of azacitidine (NSC-102816) and gemtuzumab ozogamicin (NSC-720568) as induction and post-remission therapy in patients of age 60 and older with previously untreated non-M3 acute myeloid leukemia: SWOG S0703 protocol—Report on the good-risk patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6502-6502 ◽  
Author(s):  
Sucha Nand ◽  
Holly Gundacker ◽  
John E. Godwin ◽  
Cheryl L. Willman ◽  
Thomas Norwood ◽  
...  
Keyword(s):  
Residual Disease ◽  
Early Death ◽  
Gemtuzumab Ozogamicin ◽  
Outpatient Setting ◽  
Induction Treatment ◽  
Hematologic Toxicity ◽  
Standard Chemotherapy ◽  
Global Methylation ◽  
Grade 3 ◽  
Good Risk

6502 Background: In pts with AML, response rates to standard chemotherapy decrease and early death rates increase with age. Whereas pts < 56 yrs of age have a complete remission (CR) rate of 65% and 30 day mortality risk of <3%, the respective figures are 33% and 31% in pts > 75 yrs. This trial was designed to improve safety and efficacy by using agents with low toxicity, different mechanisms of action and possible synergy. The treatment could be given in the outpatient setting. Methods: Newly diagnosed pts with non-M3 AML, 60 yrs or older, were treated as follows: Induction: Hydroxyurea 1500 mg b.i.d till WBC <10,000/mcL, followed by azacitidine 75 mg/m2/day s/cu or iv days 1-7, gemtuzumab ozogamicin (GO) 3mg/m2 on D8. Induction treatment was repeated for residual disease on D14. Pts achieving CR received a consolidation treatment identical to the induction treatment. This was followed by 4 cycles of azacitidine 75/m2/day, D1-7, given q 4 weeks. Subsequent therapy was optional. Promoter and global methylation studies were performed at defined time points. Results: Pts were stratified into good risk (age 60-69 or Zubrod 0-1) and poor risk (age ≥70 and Zubrod 2 or 3) groups. The results presented here are from the good risk cohort. Eighty-three pts were entered of whom 79 are evaluable. Median age was 71 yrs (60-88) and 49 were males. Thirty-five achieved CR/CRi (44%: 95% CI 33%-56%). Median overall survival was 11 months and median relapse-free survival with patients achieving a CR/CRi was 8 months. Six patients (8%), 3 with disease progression, died within 30 days of registration. The main non-hematologic toxicity was neutropenic fever (Grade 3 or higher), seen in 27 patients. Conclusions: The combination of hydroxyurea, azacitidine and GO is associated with a low induction mortality, can be given in the outpatient setting and produces results which compare favorably with standard chemotherapy regimens in elderly patients with AML. Our results are sufficiently encouraging to warrant further studies of this approach. Clinical Trials.govIdentifier: NCT00658814.

scholarly journals Daratumumab in Combination with Vincristine or Nelarabine As Effective Salvage Therapy for Patients with Acute Lymphoblastic Leukemia at High Risk of Relapse

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5206-5206 ◽  
Author(s):  
Yishai Ofran ◽  
Chezi Ganzel ◽  
Shimrit Harlev ◽  
Ilana Slouzkey ◽  
Ofrat Beyar Katz ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Salvage Therapy ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Donor Lymphocyte Infusion ◽  
High Dose ◽  
Molecular Remission

Abstract Acute lymphoblastic leukemia (ALL) relapsing after allogeneic stem cell transplantation (allo-SCT) is usually associated with poor outcome. T-ALL patients relapsing early post-allo-SCT or relapsed B-ALL patients who have failed currently available targeted and immunotherapies need an effective salvage therapy. We herein describe 3 cases where minimal residual disease (MRD) negative remission was achieved in very high-risk relapsing ALL patients with the use of daratumumab with or without nelarabine. Patient 1: A 24-year-old male diagnosed in May 2016 with T lymphoblastic lymphoma. Following ECOG 2993-based induction, his PET became negative. Additional 3 high-dose methotrexate and 3 consolidation cycles were prescribed followed by maintenance therapy. In August 2017, he relapsed in the bone marrow (BM) and central nervous system, and a second remission (CR2) was achieved after therapy with mitoxantrone + cytarabine. He underwent allo-SCT from his matched brother in CR2. Three and a half months after the transplant he experienced a third relapse. Two cycles of nelarabine were administrated followed by daratumumab 16mg/kg in a "myeloma like" protocol. BM at the end of 2 nelarabine cycles demonstrated remission but with 0.09% residual disease cells on flow cytometry. After the first 2 months of daratumumab, BM confirmed MRD eradication. One dose of 5x105/kg donor lymphocyte infusion (DLI) was also prescribed. Patient 2: A 43-year-old female diagnosed with T-ALL in February 2017. Her disease was refractory to ECOG 2993-based induction and remission was achieved only after a second-line therapy with mitoxantrone + cytarabine. She was referred to allo-SCT from her matched sister, engrafted well and developed grade 2-3 acute graft-versus-host disease which responded well to steroids. Five months post-transplant an extra-medullary relapse was diagnosed in her eye and skin, while MRD was identified in her BM. The same regimen of 2 cycles of nelarabine followed by daratumumab 16mg/kg was prescribed. Extra-medullary disease was eliminated and so was the residual BM disease. One dose of 5x105/kg DLI was also prescribed. The case of patient 3 has just been published (Ganzel C, et al. Haematologica, June 2018). In brief, this is a 21-year-old man diagnosed 7 years ago with Ph+ B-ALL. Daratumumab was prescribed to treat his 7th relapse after he had been treated with multiple TKIs, including ponatinib, underwent two allo-SCTs and received immunotherapy with 2 different anti CD19 and anti CD22 CAR-T cell agents. In parallel to daratumumab, vincristine was administered every 4 weeks as well as daily ponatinib. Molecular remission following daratumumab was confirmed by PCR for BCR/ABL. Kinetics of response and duration of follow-up: For the patient with Ph+ ALL, daratumumab was prescribed while overt disease was present in the BM but peripheral counts were low (WBC=2,000, ANC=1,000, PLT=95,000). Hematologic remission was confirmed after 1 month and molecular remission after 4 months. Unfortunately, 6 months after the first infusion of daratumumab he relapsed again and now (one year post-daratumumab administration) he is alive and treated with bortezomib and gemtuzumab ozogamicin. Both T-ALL patients achieved morphologic remission with nelarabine and received one DLI. MRD was identified in BM examination following nelarabine cycles and its elimination was confirmed in the BM at the end of the first 2 months of daratumumab (a total of 8 weekly infusions). Currently, these patients are 20 and 22 weeks following relapse and are alive and in molecular remission. In all 3 patients we noticed no significant side effects that could be related to daratumumab infusion. Peripheral WBC and PLT count dynamics are shown in figure 1. Treatment of ALL patients who relapse with high-risk features is a great challenge. Herein we report three consecutive patients who achieved MRD negativity with daratumumab. Daratumumab can be combined with other effective agents in a simple and safe protocol that may be delivered even to heavily pre-treated patients. Although larger studies with longer follow-up are required, this novel approach may offer new hope for patients with a devastating disease such as relapsed ALL. Disclosures Ofran: Novartis: Other: Served on a Novartis advisory board.

Minimal Residual Disease by Flow Cytometry in Children with Acute Lymphoblastic Leukemia. Single-Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4238-4238
Author(s):  
Marcela Eugenia Soria ◽  
Marcela Ema Gutierrez ◽  
Maria Isabel Gaillard ◽  
Maria Cores ◽  
Gimena Gil ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Residual Disease ◽  
Risk Group ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Wbc Count ◽  
Minimal Residual

Abstract Abstract 4238 Introduction: Minimal residual disease (MRD) allows detection of blasts in patients in morphologically complete remission. Detection of MRD in patients with ALL is an independent risk factor associated with lower event-free survival (EFS). Objectives: 1) Evaluate MRD in bone marrowaspirateby flow cytometry at days 15 and 33 of induction in children with ALL. 2) Determine MRD association with hematologic features. 3) To correlate MRD association with overall survival (OS) and event-free survival (EFS). Design and Statistical Analysis: Descriptive, retrospective study. Univariate analysis was performed by T- test for continuous varibles and byχ2or Fisher tests for categorical variables. Survival was estimated with Kaplan Meier method. Regression multiple was used for multivariate analysis. p values < 0.05 were deemed as statistically significant. SPSS 15.0 program was used for the analyses. Patients: From January 2006 to December 2009, 84 patients with newly diagnosed ALL, aged 1 –18 years, were admitted at our institution. They were treated according to ALLIC / BFM / GATLA 2002 protocol. Immunophenotypic studies were performed by standard Four-color flow cytometry (FC) using FACSCalibur BD cytometer, MDR follow up panels were tailored depending on aberrant finding at diagnosis. 300.000–500.000 events were acquired using the CellQuest Pro and Paint -a-gate software for data analysis. MDR status has been defined as positive if at least 30–50 clustered events displaying leukemia –associated immunophenotypic characteristics (0,01%). Results: The mean age at diagnosis was 7.7 years (r: 2.1–18). Mean follow-up 33.9 months (r: 1–66). 38% were female. Immunophenotype: Pro B 5%, common B 87%, Pre B 2%, and T 6%. Good response to prednisone was achieved by 92% of patients. With regard to risk groups, the distribution was: 28% standard, 55% intermediate and 17% high. MRD at day 15 was evaluable in 66 patients (78%), being positive in 35 of them (45%). MRD at day 33 was evaluable in 75 patients (89%), being positive in 10 (12%). Conclusion: Positive MRD at day 15 was associated with: increased WBC count at diagnosis, high-risk group, higher relapse rate, lower EFS and OS. Otherwise, positive MRD at day 33 was associated: increased WBC count at diagnosis, T immunophenotype, poor response to prednisone, high risk group, lower EFS and OS. Our data indicate that positive MRD at days 15 and 33 result an independent variable of poor prognosis in children with ALL. Disclosures: No relevant conflicts of interest to declare.

80% Dose R-CHOP Is Suitable Chemotherapy for Very Elderly Patients with DLBCL

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5094-5094
Author(s):  
Anna Takahashi ◽  
Yuko Mishima ◽  
Norihito Inoue ◽  
Yoshiharu Kusano ◽  
Tadahiro Gunji ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Dose Group ◽  
Risk Group ◽  
The Elderly ◽  
Very Elderly ◽  
Full Dose ◽  
Risk Patients ◽  
Grade 3 ◽  
Chop Therapy

Abstract Introduction: R-CHOP therapy is standard chemotherapy for DLBCL. In the LNH98-5 study, CR was 75% and 5-year EFS was 63% in low-risk patients and 41% in high-risk patients. Five-year OS was 80% in the low-risk group, and 48% in the high-risk group. R-CHOP is tolerable and commonly applied to outpatients. However, almost 20% of patients with DLBCL were very elderly, 75 years of age or more. Chemotherapy for very-elderly patients often causes many troubles, and thus the prognosis is worse than those of younger patients. The dose of R-CHOP therapy for the elderly patients varies among institutions because there are no suitable guidelines for it. Therefore, the optimal dose of R-CHOP therapy is needed to be determined to improve the outcome of the elderly patients with DLBCL. Methods: We reviewed the clinical records of 91 newly-diagnosed very-elderly (≥75 years) patients with DLBCL. All of the patients were diagnosed by hematopathologists, and treated with R-CHOP-based chemotherapy in our hospital from 2005 to 2015. Clinical stage and the effect of therapy were evaluated with PET/CT scan. Statistical analyses were performed with a software, EZR version 1. Results: The total number of patients with DLBCL in the study period was 373, including 91 very-elderly patients (24%). The characteristics of very elderly patients were following; the median age was 78 years (range 75-86), the median follow-up period was 1,068 days (range 39-2,989), 49 (54%) were male, 38 (43%) were at stage III or IV, 39 (43%) had IPI high or intermediate risk, bulky disease (≥10 cm) was observed in 18 (20%), and 75 (82%) showed ECOG PS 0 or 1. Twenty-six patients (29%) were treated with R-CHOP at full dose, 64 patients (70%) at 80%, and one was at 70%. In the 80% R-CHOP group, the dose was decreased to 70% in 5 patients, because of severe adverse events (febrile neutropenia in three, grade 3 nausea and grade 3 weakness, each in one). The median ages of patients were 76 years in the full dose group (range 75-79) and 78 years in the 80% dose group (range 75-86). In the all very-elderly patients, 5-year OS was 66% (95% CI, 52-77%) and 5-year PFS was 68% (95% CI, 55-78%). CR was achieved in 73% in the full-dose group, and 67% in the 80% dose group. Five-year OS were 77% in the full-dose group, and 61% in the 80% dose group (P=0.129). Five-year PFS were 82% in the full-dose group, and 63% in the 80% dose group (P=0.117). Five-year OS were 100% in the IPI low group, 65% in the low- and high-intermediate groups, 0% in the high group (P<0.001). Twenty-six patients died: 13 for progression of lymphoma, 7 for other diseases, and 6 for unknown causes. All patients with 5 IPI indexes died of lymphoma. Twenty-one patients completed the therapy (81%) in the full-dose R-CHOP group, and 55 (86%) in the 80% R-CHOP group. In the 14 patients who could not complete the therapy, 7 achieved CR without relapse. The most frequent adverse event was hematological toxicity. Neutropenia at grade 3 or 4 was observed in 17 (19%), and febrile neutropenia in 12 (13%). No treatment-related deaths were observed. Conclusions: In the very elderly patients, there were no significant differences in 5-year OS and PFS between the full-dose R-CHOP and the 80% R-CHOP groups. Prognosis was very poor for the patients with IPI high risk, especially with 5 IPI indexes. Our data suggested that 80% dose R-CHOP is enough tolerable and effective to very elderly patients with DLBCL categorized in IPI high-intermediate or lower risks. Disclosures Mishima: Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.

Feasibility and Efficacy of Administration of Bortezomib-Containing Regimens to Patients Over the Age of 70 Years

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5035-5035
Author(s):  
Christopher Parrish ◽  
Julian Cromack ◽  
Sylvia Feyler ◽  
John Ashcroft ◽  
Roger G. Owen ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Haematological Toxicity ◽  
Sensory Neuropathy ◽  
The Elderly ◽  
Control Cohort ◽  
Light Chain Disease ◽  
Grade 3 ◽  
Elderly Cohort ◽  
And Control

Abstract Abstract 5035 Rationale: Recent studies demonstrate superiority of bortezomib-containing regimens over standard therapy at improving response rates and durability of responses in patients with multiple myeloma (MM). However, limited data exist for the feasibility of delivering bortezomib-containing regimens to patients with MM over the age of 70 years. We therefore conducted a retrospective review of administration of bortezomib in combination with pulsed Dexamethasone (Bort-Dex) in elderly patients to determine the feasibility and toxicity of delivery. Methods: Patients >70 years with MM who had received at least one prior line of treatment but had not been previously exposed to bortezomib, were assessed for their predicted tolerance to Bort-Dex: bortezomib 1.3mg/m2 IV on days 1, 4, 8 and 11 (standard) on a 21 day-cycle or on days 1, 8, 15 and 22 (modified) on a 35 day cycle, in association with dexamethasone 20mg on the day of and day after bortezomib. Treatment was discontinued at maximal disease response, if refractory disease or if treatment-related toxicity precluded further cycles. A control cohort comprised patients <70 years matched for number of prior lines of therapy treated with Bort-Dex. International Myeloma Working Group response criteria and National Institutes of Health toxicity scores were used for assessments. Results: 19 elderly patients with MM (IgG n=14; IgA n=2; light chain disease n=3) and a median age of 80 yrs (range 74, 90) were compared with 19 MM patients (IgG n=11; IgA n=3; light chain disease n=5) aged <70 yrs with a median age of 61 (range 39–70). Patients had received a median of 1 prior line of therapy (range 1, 4) in both cohorts. International staging system (ISS) scores ranged from 1 to 3 with a median of 2 in both cohorts. At diagnosis, in the elderly and control groups respectively, the median beta-2 microglobulin was 3.2 mg/l (range 1.8, 13) and 3.1 mg/l (range 2, 11.2), the median glomerular filtration rate was 49 mls/min/1.72sq.m (range 12, 69) and 71mls/min/1.72sq.m (range 14, 90), and median bone marrow plasmacytosis by flow cytometry was 13% (range 0.9, 51) and 17.2% (range 2.3, 36). Standard (n=12) and modified (n=7) dosing schedules were used in the elderly cohort, with standard dosing in the control cohort. Elderly patients received a median of 3 cycles (range 1–6) compared with a median of 4 cycles (range 1–6) in the control cohort (p=0.11).Response was not assessable in 4 patients: elderly n=3, control n=1. Response to Bort-Dex in the elderly and control cohorts, respectively: 5 (26%) and 6 (32%) patients achieved a complete response (CR) or stringent CR, 4 (21%) and 2 (11%) a very good partial response, 4 (21%) and 7 (37%) a partial response, 3 (16%) and 1 (5%) a minimal response or stable disease, 0 and 2 (11%) progressive disease. Median follow up was 5.1 months (range 0.6, 33.6) in the elderly and 12.1 months (range 0.7, 46.5) in the control cohorts. At last follow-up 7 (37%) patients in the elderly cohort had relapsed, with median time to progression (TTP) of 11.0 months (range 3.3, 16.8). In the control cohort 11 (58%) patients had relapsed with a TTP of 7.3 months (range 0, 21.3), p=0.26. In the elderly cohort, grade 3–4 haematological toxicity was reported in 2 patients (11%) with grade 3–4 non-haematological toxicity reported in 6 patients (32%): sensory neuropathy n=2, motor neuropathy n=1, fatigue n=2, infection n=2. Intensity of Bort-Dex was reduced in 5 patients, due to treatment-related toxicity. In the control cohort, grade 3–4 haematological toxicity was reported in 4 patients (21%) and grade 3–4 non-haematological toxicity in 5 patients (26%, sensory neuropathy in all cases). 2 elderly patients required hospital admission for treatment-related complications: cellulitis/varicella zoster reactivation (n=1; 23 days of admission) and bacterial sepsis (n=1; 41 days). By comparison, in the control cohort 1 patient required admission (15 days) for treatment of infective colitis. No treatment-related mortality was reported. Conclusions: Reductions in the intensity and frequency of dosing are often required in order to deliver Bort-Dex to elderly patients, though with comparable response rates to younger patient populations. Through drug delivery modifications, Bort-Dex therapy can be delivered with an acceptable adverse event profile, offering a suitable salvage therapy for elderly patients with relapsed MM. Disclosures: Cook: Orthobiotec: Consultancy, Speakers Bureau.

Early Safety and Efficacy Analysis of a Phase II Study of Sequential R-CHOP and Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) for Elderly High Risk Patients with Untreated DLBCL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 926-926 ◽  
Author(s):  
Paul A. Hamlin ◽  
Craig H. Moskowitz ◽  
Brett C. Wegner ◽  
Carol S. Portlock ◽  
David J. Straus ◽  
...  
Keyword(s):  
High Risk ◽  
Sudden Death ◽  
Elderly Patients ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Safety And Efficacy ◽  
Grade 5 ◽  
Grade 3 ◽  
Yttrium 90

Abstract Introduction: Elderly patients (pts) with high risk DLBCL represent an increasing demographic, are often underserved in clinical trials, and need improved therapies. By the age-adjusted international prognostic index (aaIPI), pts &gt;60 years (yrs) with high-intermediate (HI) and high risk (H) disease had 5 yr survival (OS) rates of 37%, and 21%, respectively. Rituximab’s addition to CHOP has improved responses and outcomes, but &gt;50% of high risk pts still relapse. We are investigating the safety and efficacy of sequential RCHOP followed by Yttrium-90 ibritumomab tiuxetan (Zevalin ®) radioimmunotherapy (RIT) in an effort to improve these results. An early safety analysis of this sequential program is presented here. Methods: Untreated ASCT-ineligible pts &gt;60 yrs, with aaIPI HI or H risk DLBCL are eligible for study. Induction: pts receive R-CHOP chemotherapy at standard doses q 21 days x 6 cycles with prophylactic pegfilgrastim (or G-CSF) and darbepoetin alfa (Aranesp ®) support. Consolidation: pts with ≥ stable disease at post RCHOP restaging are eligible for 90Y-90 ibritumomab tiuxetan, given 6–9 weeks post RCHOP; For platelet (plt) counts ≥ 150K → 0.4 mCi/kg dose, plt counts of 100–149K → 0.3 mCi/kg. Weekly CBC’s are performed until week 12–13 restaging. Results: 26 pts have been enrolled as of July 12th, 2005. Median age is 75 (range 65–85; male:female 9:17); KPS &lt;80% in 55% (median 70%, range 60–90%); LDH &gt; nl: 89% (range 150–804); Stage III/IV: 11.5% / 88.5 %; Extranodal sites are &gt;1 in 50%; B symptoms in 54%; aaIPI HI (2 factors) = 46%, H (3 factors) = 54%; 18/26 pts have completed RCHOP; 8 pts are off study before RIT for: 4 cardiovascular events (1 CHF,1 Non-Q-wave MI, 1 sudden death, 1 V. Fib arrest), 3 neutropenic sepsis (1=grade 4, 2=grade 5), 1 leptomeningeal progression; 14 pts have received RIT. Median nadir counts during RIT occur at week 6–7: absolute neutrophil count (ANC) = 850 cells/mm3 (0.3–5.4), Hemoglobin (Hgb)= 10.1 gm/dl (6.6–14.6), plt = 28K cells/mm3 (7–103); Grade 3 and 4 ANC = 39%/39%, Hgb 39%/0%, Plt 46%/15%; During RIT, blood and Plt transfusion occurred for 46% and 31%, respectively; colony stimulating factor and erythropoietic support was used in 39% and 31%, respectively. One pt had delayed count recovery post RIT (448 days, transfusion independent from week 12→). Non-hematologic serious adverse events after RIT include: two grade 3 neutropenic infection (1 without fever), 1 grade 5 sudden death at week 7 (autopsy refused). OS and EFS for all pts by intent to treat is 60% and 55%, respectively, with 14 months median followup. Of pts post-RIT &gt;12 weeks (11 pts), none have relapsed with 21 months median follow-up. Conclusions: Treatment of elderly aaIPI HI and H risk DLBCL pts with sequential RCHOP followed by 90Y ibritumomab tiuxetan is feasible and associated with manageable toxicity. Hematologic toxicity with RIT is similar to single agent toxicity, with slightly greater thrombocytopenia that warrants careful follow-up. Toxicity during RCHOP induction is significant in high risk elderly patients and cycle one modification is being implemented. Accrual continues to evaluate the potential long term impact of RIT on EFS and OS.

Clinical outcomes and rates of molecular remission with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) combination therapy in newly diagnosed acute promyelocytic leukemia (APL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6503-6503 ◽  
Author(s):  
A. M. Tsimberidou ◽  
H. M. Kantarjian ◽  
G. Garcia-Manero ◽  
C. Koller ◽  
D. M. Jones ◽  
...  
Keyword(s):  
High Risk ◽  
Combination Therapy ◽  
Complete Response ◽  
Gemtuzumab Ozogamicin ◽  
Low Risk ◽  
Molecular Remission ◽  
All Trans Retinoic Acid ◽  
Improved Outcomes ◽  
Grade 3

6503 Background: ATRA and anthracyclines provide durable remissions in patients with untreated APL. As2O 3 has improved outcomes in untreated and relapsed/refractory APL. The aim of this study was to determine the rates of complete response (CR) and molecular remission with ATRA and As2O 3 combination therapy in untreated APL. Methods: From 2/02 to 1/06, 53 patients with untreated APL received ATRA 45 mg/m2 daily and As2O 3 0.15 mg/kg IV 1-hr infusion daily starting on day 10. Patients with WBC>10×109/L also received gemtuzumab ozogamicin (GO) 9 mg/m2 on day 1 and/or idarubicin 12 mg/m2 on days 1–4. Patients in CR received As2O 3 0.15 mg/kg IV on days 1–5 weekly for 4 weeks on and 4 weeks off and ATRA 45 mg/m2 daily for 2 weeks on and 2 weeks off (for 28 weeks). Polymerase chain reaction (PCR) testing for PML-RARα (sensitivity level, 10−4) was performed every 3 months from CR for 2 years. Patients with molecular relapse received GO 9 mg/m2 once monthly for 3 months in addition to ATRA and As2O 3 as in postremission therapy. If PCR became negative, only the single dose of GO was given. Results: The median age was 46 years; and 20% of patients were Sanz low risk, 40% intermediate, and 40% high risk. The CR rate was 91% (low risk 91%, intermediate 95%, high risk 86%). The median follow-up in surviving patients was 1.6 years. Six patients died during induction, and 2 died in CR from other cancers. The 1-yr survival rate was 88%. Three patients relapsed (at 9, 9, and 16 months). The 1-yr failure-free survival (FFS) rate in responding patients was 94% (high risk 86%, other risk 100%). Molecular remission rates are shown in the Table . Grade 3–4 nonhematologic toxicities were infections (n=16), neurologic (n=4), cardiac arrhythmias (n=4), APL differentiation syndrome (n=4), and headache (n=2). Conclusions: ATRA plus As2O 3 results in high rates of CR, molecular remission, FFS, and survival and is an alternative to ATRA and idarubicin combination therapy in low-risk APL. [Table: see text] No significant financial relationships to disclose.

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