Follicular Lymphoma In Young Adults: Clinical Characteristics and Early Treatment Outcomes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4273-4273 ◽  
Author(s):  
Shane A Gangatharan ◽  
John Kuruvilla ◽  
Vishal Kukreti ◽  
Rodger E. Tiedemann ◽  
Mary Gospodarowicz ◽  
...  
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Follicular Lymphoma ◽  
Treatment Outcomes ◽  
Older Patients ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Univariable Analysis ◽  
Significant Difference

Abstract Introduction Adolescents and young adults with hematologic malignancies have distinct tumor biology, treatment outcomes and psychosocial consequences from cancer diagnosis and its treatment. Follicular lymphoma (FL) is generally considered to be a disease of the elderly, with a median age at diagnosis of 67 years and 65% of patients 60 years or older. FL is rare among young adults (age<40, YA), and the clinical features, natural history and treatment outcomes have not been well defined in this vulnerable patient population, who have unique life challenges while facing what is often considered an incurable lymphoma. We describe the characteristics and outcomes of a large group of YA with newly diagnosed FL treated at our center and compare them to older patients Methods The Princess Margaret Cancer Centre lymphoma database was interrogated for patients registered with FL between 1995 and 2009. Database and retrospective chart review was undertaken to collect data on FLIPI score at diagnosis, time to first and subsequent second treatments, histologic transformation and overall survival (OS). Outcomes were compared between YA and older patients (age 40-65). The older age group was limited to< 65 years to ensure comparable therapies, and because patients in this age range may be potentially eligible for intensive therapy including stem cell transplantation. Results 410 patients with newly diagnosed FL were identified. Stage at diagnosis: I:34.1%; II: 18.3%, III: 21%, IV: 26.7%; FLIPI score: 0 22.9%, 1: 25.8%, 2: 32.8%, 3: 15%, 4: 2.6%, 5: 1%. Fifty five patients (13.4%) were age< 40 at diagnosis. Median age in the YA cohort was 36 years, and 53 years in the older adults. Chi-square testing showed no difference in sex, stage or FLIPI score at diagnosis between YA and older adults. Initial treatment consisted of observation in 105 patients (25.7%); 11 of those managed expectantly were YA. With median follow-up in the observed group of 7.3 years (range 0.68-14.64), 52.3% required therapy (radiation, chemotherapy or combined modality), with median time to therapy from diagnosis of 22 months. Among all patients eventually treated, intial treatment included chemotherapy alone in 37.4%, radiotherapy in 33.8% and combined modality therapy in 25.6%. The most common chemotherapy regimens were CHOP and CVP, alone or with rituximab. Probability of requiring second treatment following initial radiation or chemotherapy was 54.5% at 2 years. FLIPI score strongly predicted time to second treatment (0=0.0047). Time to second treatment was similar for those initially observed compared to those receiving treatment at time of diagnosis, and for young compared to older adults. For the entire cohort, with median follow-up of 8.1 years (range 0.34-17.75), 5-year OS was 86.9%. On univariable analysis there was a significant difference in survival between YA and older patients: 10-year OS 89.3% v 74.2%, p=0.04. On analysis of lymphoma-specific death, there was lower probability of death in YA at 10 years: 4% compared to 15.3% for older adults, although this was not statistically significant (p=0.088). There was no significant difference in survival for patients initially observed compared to those receiving therapy at diagnosis (10-year OS 82.9% v 74%, respectively, p=0.18). Multivariable analysis demonstrated that FLIPI score at diagnosis and age<40 were significant independent variables predictive of OS. Furthermore, despite lack of significance on univariable analysis, in this model patients managed initially with observation had significantly improved OS compared to patients treated at diagnosis with radiation, chemotherapy or both (HR 2.05, p=0.0223). Histologic transformation occurred in 53 patients, 8 in YA (14.5% of all YA) and 45 in the older cohort (12.7% of all older patients). Conclusions YA with follicular lymphoma present with similar clinical characteristics to older patients, and comparable proportions of patients requiring therapy at diagnosis for symptomatic disease. YA demonstrate improved OS independent of FLIPI score compared to older adults. Whether this reflects competing mortality risks or age-related differences in lymphoma biology warrants further investigation. Disclosures: Kuruvilla: Roche: Honoraria. Kukreti:Millennium Pharmaceuticals: Research Funding; Onyx: Research Funding. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Crump:Roche: Honoraria; Jansen-Ortho: Honoraria; Celgene: Honoraria; Lundbeck: Honoraria; Novartis: Research Funding; Seattle Genetics: Honoraria.

scholarly journals Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Chemotherapy Provides Very Good Outcome in Older Patients with Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: First Results from the EWALL-INO Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 511-511
Author(s):  
Patrice Chevallier ◽  
Thibault Leguay ◽  
Michael Doubek ◽  
Francoise Huguet ◽  
Cyril Salek ◽  
...  
Keyword(s):  
B Cell ◽  
Older Patients ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Newly Diagnosed ◽  
Cell Precursor ◽  
Inotuzumab Ozogamicin ◽  
Low Intensity

Abstract On behalf of the GRAALL group, the Czech Republic ALL group, the Finland ALL group and the EWALL group. Introduction. Treatment of older patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains an unmet medical need. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, is approved for the treatment of relapsed/refractory BCP-ALL in adults, sinusoidal obstruction syndrome (SOS) being the major adverse event associated with INO. A previous first line study conducted by the MDACC in pts 60 years or older successfully used INO in combination with a lower intensity version of the hyper-CVAD (mini-hyper-CVD). Due to the occurrence of SOS, the total doses were fixed at 1.3 mg/m² for cycle 1 followed by 3 cycles at 1 mg/m² (Kantarjian H et al. Lancet Oncol, 2018). Here, we aimed to assess the activity and safety of fractionated INO at a reduced dosage in combination with low-intensity chemotherapy as frontline therapy for older pts with CD22+ Philadelphia chromosome-negative (Ph-neg) BCP-ALL. Methods. EWALL-INO is a single arm prospective phase 2 multicentric study conducted in European centers belonging to the EWALL group. Eligibility criteria were pts aged 55y or older, performance status ≤2, and newly diagnosed CD22+ (20% or more of positive blast cells) Ph-neg BCP-ALL without central nervous system involvement. After a prephase including 5 days (D) of dexamethasone (DEX) 10mg per D and a single intrathecal injection (IT), the induction regimen was begun and split in 2 parts. Induction part I (Induc1) consisted of one triple IT, vincristine (VCR) 2 mg (1 mg over 70y) D1 D8 D15 D22 and DEX 20 mg D1D2 D8D9 D15D16 D22D23 combined with 3 injections of INO (0.8 mg/m² D1, 0.5 mg/m² D8 and D15). Induction part II (Induc2) was offered to pts in CR or CRp (CR with platelets &lt; 100 G/l) after Induc1 or as salvage therapy. Induc2 consisted of DEX 20mg D1D8, cyclophosphamide (CY) 300 mg/m² D1 to D3, one triple IT D2 and 2 injections of INO (0.5 mg/m² D1 and D8). Pts in CR/CRp were programmed to receive 6 blocks of consolidation (Ara-C 1.5g/m²/12h adapted to renal clearance D1D2 and DEX 10mg/12h D1D2, cycles 1 and 4; Methotrexate (MTX) 1.5 g/m² over 24h D1, VCR 1 or 2 mg D1, one triple IT D2 and 6-mercaptopurin (6-MP) D1 to D7, cycles 2 and 5; CY 500 mg/m² D1D2, VP16 75 mg/m² D1D2, one triple IT D2 and MTX 25 mg/m² D1, cycles 3 and 6) followed by a POMP maintenance (VCR, 6-MP, MTX, DEX) during 18 months. Allograft was allowed after at least 3 blocks of consolidation at the discretion of the investigators. The evaluable population was pts who received at least 1 dose of INO. Analyses were by modified intention to treat and performed JUN 28, 2021. All pts gave informed consent. The study is registered at ClinicalTrials.gov under the NCT number: NCT03249870. Results. Between DEC 29, 2017 and JUN 22, 2021, 115 pts (out of 130 planned pts) were enrolled including 6 pts with screen failure. The first 90 eligible pts (up to MAR 1, 2021) were considered for this analysis to obtain a minimum of 4 months follow-up. Median age was 69y (range 55-84) and median follow-up for alive pts was 1.18 years (range 0.3-3.5). At time of analysis, 90 and 88 pts had started induc1 and induc2, respectively. Treatment related mortality was 2.2% (2/90) and CR/CRp rate was 85.5% (77/90, 6 CRp) after induc1. Three cases relapsed between induc1 and induc2 and 5 pts were salvaged by induc2 allowing to a CR/CRp rate of 87.7% (79/90, 8 CRp) after induc2. One pts died from refractory disease during induc2. One, 2, 3 4 and 5 injections of INO were administered to 2 (2.2%), 2(2.2%), 11 (12.2%), 2 (2.2%) and 73 pts (81.1%) respectively. Only 6 pts were allografted. One-year OS was estimated to be 78.5% (95%CI 68-85.9) and median OS was not reached. One-year relapse free survival was 74.5% (95CI 63.5-82.6) (Figure 1). Grade 3-4 liver toxicity was observed in 8 pts (8.8%) during the study including 3 pts (3.3%) developing SOS, 2 related to INO during induc1 and one occurred after transplant. Twenty-nine pts died during the follow-up, 16 from relapses (overall incidence 18%) and 13 from adverse events (overall incidence 14.4%), including one COVID19 fatal infection during consolidation. Conclusion. Fractionated inotuzumab ozogamicin at reduced doses (0.8/0.5/0.5/0.5 mg/m²) combined with low-intensity chemotherapy is a very active and well tolerated frontline therapy for older patients with CD22+ Ph-neg BCP-ALL. Figure 1 Figure 1. Disclosures Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Huguet: Novartis: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Celgene: Other: Advisor; BMS: Other: Advisor; Amgen: Other: Advisor; Pfizer: Other: Advisor. Raffoux: ABBVIE: Consultancy; PFIZER: Consultancy; CELGENE/BMS: Consultancy; ASTELLAS: Consultancy. Boissel: CELGENE: Honoraria; Servier: Consultancy, Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; PFIZER: Consultancy, Honoraria; JAZZ Pharma: Honoraria, Research Funding; SANOFI: Honoraria. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Inotuzumab ozogamicin as first line therapy in newly diagnosed CD22+ Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia

scholarly journals Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients Enrolled in CPX-351-301, a Randomized Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, High-Risk and/or Secondary AML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 44-45
Author(s):  
Geoffrey L Uy ◽  
Laura F. Newell ◽  
Tara Lin ◽  
Stuart L. Goldberg ◽  
Matthew J. Wieduwilt ◽  
...  
Keyword(s):  
Older Adults ◽  
High Risk ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Phase 3 ◽  
Secondary Aml ◽  
Donor Type

Background: CPX-351 is a liposomal encapsulation of daunorubicin and cytarabine in a 1:5 molar ratio. In a randomized phase 3 study (CPX-351-301) conducted in older adults (60 to 75 years old) with newly diagnosed, high-risk and/or secondary AML, CPX-351 induction therapy was superior to standard 7+3 with improved rates of complete remission (CR) and overall survival (OS). In both older adults and high-risk AML, allogeneic hematopoietic cell transplantation (HCT) is frequently the preferred post-remission strategy owing to the high rates of relapse and poor overall survival with conventional chemotherapy approaches. After a median follow-up of 20.7 months, the primary pre-planned analysis found that more patients randomized to CPX-351 underwent HCT and an exploratory landmark survival analysis from the time of HCT favored CPX-351 (HR = 0.46 [95% CI: 0.24, 0.89]; one-sided P = 0.009). However, the initial protocol did not collect data related to HCT and the basis for improved HCT outcomes with CPX-351 was previously unknown. Here we present a detailed analysis of HCT outcomes in patients enrolled in the CPX-351-301 study with 5-years of follow-up. Methods: Patients age 60 to 75 years with high-risk and/or secondary AML were randomized in a 1:1 fashion to receive CPX-351 or 7+3 as induction and consolidation chemotherapy (Lancet J et al, JCO 2018). The protocol was amended to collect additional HCT-specific information, including donor and HCT characteristics and post-HCT outcomes, including rates of relapse and GVHD. Post-HCT outcomes including relapse, GVHD, and death were analyzed as competing events. Results: Of 309 randomized patients in the CPX-351-301 study, more patients achieved CR/CRi with CPX-351 vs 7+3 (48% vs 33%) allowing more patients to proceed to HCT (35% vs 25%) and more patients to proceed to HCT in remission (CPX-351: 41/73 [56%]; 7+3: 24/52 [46%]). The median age was 66 years with CPX-351 vs 65 years with standard induction among the transplanted cohorts; 16 patients in the CPX-351 transplanted arm were over the age of 70 compared to only 6 in the 7+3 arm. Other pre-HCT patient characteristics were balanced between the CPX-351 and 7+3 groups, including ECOG performance status (8% vs 5% with ECOG PS of 2), HCT-CI (median 4 vs 3), donor type (matched unrelated donor 49% vs 49%), and conditioning regimen intensity (myeloablative [17% vs 13%] vs reduced-intensity conditioning [43% vs 46%]). The Kaplan-Meier-estimated 3-year survival rate among transplanted patients was 56% with CPX-351 vs 23% with 7+3 (Figure 1A). The differences in survival consistently favored CPX-351 across patient age, AML subtype, disease status, donor type, and conditioning intensity (Figure 1B). Differences in OS were driven by a large reduction in non-relapse mortality (HR = 0.42 [95% CI: 0.21, 0.86]; Figure 1D). The cumulative incidence of acute GVHD with death as a competing event at 6 months from HCT date was 0.49 (95% CI: 0.35, 0.62) in the CPX-351 arm and 0.38 (95% CI: 0.23, 0.53) in the 7+3 arm. Conclusions: Analysis of HCT outcomes in patients enrolled in the CPX-351-301 study demonstrated that treatment with CPX-351 in older adults with high-risk and/or secondary AML resulted in more patients bridged to HCT and more patients transplanted in CR/CRi compared to 7+3, with improved OS in transplanted patients. The pattern of HCT outcomes suggests improved disease control with CPX-351 induction allowing higher HCT rates, but more importantly improved tolerability with less non-relapse mortality; this data supports the development of CPX-351 in other high-risk AML populations in which allogeneic HCT is the preferred post-remission strategy. Figure Disclosures Uy: Genentech: Consultancy; Agios: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas Pharma: Honoraria; Jazz Pharmaceuticals: Consultancy. Lin:Abbvie: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Prescient Therapeutics: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; Ono Pharmaceutical: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Gilead Sciences: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Aptevo: Research Funding. Wieduwilt:Reata Pharmaceuticals: Current equity holder in publicly-traded company; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Merck: Research Funding; Leadiant: Research Funding; Amgen: Research Funding; Macrogeneics: Research Funding. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

scholarly journals Impact of Bortezomib- or Lenalidomide-Based Induction Treatment on High Risk Cytogenetic Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Enrolled in the Gimema-MM-03-05 and EMN01 Trials

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 744-744 ◽  
Author(s):  
Alessandra Larocca ◽  
Massimo Offidani ◽  
Pellegrino Musto ◽  
Francesca Patriarca ◽  
Lorenzo De Paoli ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Significant Difference ◽  
Reduced Risk

Abstract Introduction : Cytogenetic abnormalities by fluorescence in situ hybridization (FISH) are clinically relevant prognostic factors in MM. Data in transplant ineligible patients treated with bortezomib or lenalidomide in first-line therapy for high-risk (HiR) patients is limited. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. This sub-analysis evaluates the impact of cytogenetics on outcomes in transplant-ineligible patients with newly diagnosed MM (NDMM) treated with bortezomib-based induction (BORT) or lenalidomide-based (LEN) treatment. Methods : In the GIMEMA-MM-03-05-trial, patients were randomized to bortezomib-melphalan-prednisone-thalidomide for 9 cycles followed by maintenance with bortezomib-thalidomide (VMPT-VT) vs VMP for 9 cycles, without maintenance. In the EMN01-trial, patients were randomized to melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus low-dose dexamethasone (Rd) for 9 cycles, followed by maintenance with lenalidomide alone or plus prednisone continuously. Results of these studies have previously been reported (Palumbo A et al JCO 2010 and 2014; Magarotto V et al Blood 2016 127(9)). Cytogenetics were assessed using FISH. Patients were categorized into cytogenetic risk groups according to International Myeloma Working Group criteria. HiR cytogenetics included del(17p), t(4;14), and t(14;16); all other patients were categorized as standard risk (StR). Subgroup analyses were performed to determine the consistency of treatment effects of BOR vs LEN in the different subgroups using interaction terms between treatment and FISH, ISS, age, sex, Karnofsky PS and LDH. The different effect of BORT vs LEN in cytogenetic subgroups was confirmed by one sensitivity analysis where the follow-up of the BORT study was reduced to make the follow-up times similar; and by another sensitivity analysis with multiple imputation method for missing cytogenetic value. Results : 902 of 1165 patients from the intent-to-treat population had available cytogenetic profiles, with 243 (27%) patients in the HiR group and 659 (73%) in the StR group. In the BORT vs LEN groups, median age was 71 vs 73 years (p&lt;0.001), ISS3 20% vs 27% (P=0.65), HiR patients were 29% vs 26%, StR patients were 71% vs 74% (p=0.32) and the median follow-up was 72.3 and 63.6 months, respectively. In the subgroup analysis, a significant difference was found in the cytogenetic subgroup with a superior advantage of BORT versus LEN in HiR group, whereas no significant difference was found between BORT and LEN in the other subgroups analyzed (ISS, age, sex, Karnofsky PS and LDH) (interaction-p=0.01) (Fig. 1 B). BORT treatment resulted in a reduced risk of death or progression compared with LEN in patients with HiR. In HiR patients, median PFS was 30.8 with BORT compared with 14.8 months with LEN (HR: 0.54; 95% CI: 0.41-0.72); in StR, median PFS was 29.1 with BORT compared with 22.1 months with LEN (HR: 0.87; 95%; CI: 0.72-1.05) (Fig. 1 A). Considering the standard of care VMP and Rd, in the HiR group (n=95) VMP resulted in a 48% reduced risk of death or progression compared with Rd (HR: 0.53; 95% CI: 0.34-0.83), whereas no significant difference in PFS was found in the StR group (n=273) (HR: 1.00; 95% CI: 0.75-1.33), interaction-p=0.02. BORT treatment resulted in a reduced risk of death in patients with HiR cytogenetics: median OS was 62.4 months with BORT compared with 43.2 months with LEN (HR: 0.68; 95% CI: 0.47-0.96); in StR, median OS was 78.1 months with BORT and was not reached with LEN (HR: 1.06; 95% CI: 0.82-1.36), interaction-p=0.04 (Fig. 1 A). In patients with del(17p) (n=131) median PFS was 18.0 vs 12.9 months for BORT vs LEN (HR: 0.71; 95% CI: 0.49-1.04), interaction-p=0.73. In patients with t(4;14) (n=118) median PFS was 31.5 vs 15.2 months for BORT vs LEN (HR: 0.41; 95% CI: 0.27-0.62) interaction-p=0.002. In patients with t(14;16) (n=31) median PFS was 36.2 vs 9.8 months for BORT vs LEN treated patients (HR: 0.34; 95% CI: 0.16-0.76), interaction-p=0.045. Conclusions : BORT treatment resulted in a PFS and OS benefit vs LEN in patients with HiR cytogenetics. Treatment with VMP led to a significant reduction of the risk of death or progression vs Rd in HiR patients. These results support VMP induction as a standard treatment option for patients with NDMM who are ineligible for transplant with HiR cytogenetics. Disclosures Larocca: Celgene: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria. Offidani: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto: Janssen: Honoraria; Celgene: Honoraria. Patriarca: MSD Italia: Honoraria; Janssen: Honoraria. Corradini: Gilead: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Bosi: Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Petrucci: Celgene: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Boccadoro: Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding; AbbVie: Honoraria.

scholarly journals Variant Allele Frequency Status in Elderly Patients with Acute Myeloid Leukemia Can be Early Predictors of Responsiveness to Decitabine Treatment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3450-3450
Author(s):  
Mihee Kim ◽  
Taehyung Kim ◽  
Seo-Yeon Ahn ◽  
Sung-Hoon Jung ◽  
Ga-Young Song ◽  
...  
Keyword(s):  
Older Adults ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Survival Outcome ◽  
Newly Diagnosed ◽  
Variant Allele Frequency ◽  
Early Predictors ◽  
Targeted Ngs ◽  
Better Than

Abstract As interest in elderly Acute Myeloid Leukemia (AML) patients increases, American society of hematology (ASH) 2020 guidelines for treating newly diagnosed AML in older adults suggested diverse treatment options. The guidelines suggest using monotherapy over combination of hypomethylation agent (HMAs) with other agents in newly diagnosed AML in older adults due to similar efficacy and the potential for more toxicity. HMAs alone is still used widely as an alternative treatment for patients who cannot use venetoclax due to the high cost and poor performance score. If there are early predictors of responsiveness to Decitabine mono therapy, it will be helpful to decide whether to combine Novel agents. This retrospective cohort study from a single institution aimed to evaluate the prognostic significance of Variant allele frequency (VAF) changes in elderly patients after 4 th cycle of decitabine. Total 123 patients with elderly AML were eligible. 57 patients performed follow-up bone marrow biopsy and 49 patients were available of follow up targeted NGS samples from biopsy after 4th cycle of decitabine. To clarify the immortal timed bias, landmark analyses were performed with patients (n=84) who remained at least the median time to perform follow-up bone marrow biopsy after 4th cycle of decitabine treatment. 24 patients (54.5%, 24 of 44) showed more than 50% decrease of VAF after 4 th cycle of decitabine (figure 1a). DMNT3A, TET2, IDH1, IDH2, and SETBP1 and SMC1A showed less than 50% of the decreases of VAF. Patients with DNA methylation genes showed significantly reduced VAF less than 50% (figure 1b). A significant difference of ∆VAF was observed depending on CR status (p=0.021). The survival outcome of patients who showed more than 50% decrease of initial VAF after 4th cycle of decitabine was significantly better than that that with less than 50% decrease of VAF(1-year OS VAF decrease ≥ 50% (n=23), 75.0%; VAF decrease &lt; 50% (n=20), 38.5%; no mutation (n=12), 45.5%; not available of follow up targeted NGS sample (n=29), 16.6%; p &lt; 0.001, figure 2a). Mutations in DNMT3A, TET2, and ASXL1 (DTA genes) were detected in samples from 19 patients at diagnosis. After the exclusion of DTA mutations, the survival outcome improved prognostic risk stratification power of NGS-based MRD assessment in AML. The survival outcome of patients who showed more than 50% decrease of initial VAF after 4th cycle of decitabine was significantly better than that that with less than 50% decrease of VAF(1-year OS VAF decrease ≥ 50% (n=24), 75.0%; VAF decrease &lt; 50% (n=19), 35.1%; no mutation (n=12), 50.1%; not available of follow up targeted NGS sample (n=29), 16.6%; p&lt;0.001, figure 2b). In conclusion, more than 50% decrease of VAF was important negative prognostic factors by improving overall response rate and OS. In case of patients with older adults who received decitabine treatment, if follow up BM biopsy after 4 th cycles of decitabine treatment showed more than 50% reduction of VAF, it may suggest to maintain decitabine treatment. However, if VAF is reduced by less than 50% in follow up BM biopsy, the residual disease burden is considered for the selection of combination treatment to improve survival outcome. Figure 1 Figure 1. Disclosures Kim: Bristol-Meier Squibb: Research Funding; Paladin: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals A Pediatric-Inspired Regimen Containing Multiple Doses of Intravenous Pegylated Asparaginase Appears Safe and Effective in Newly Diagnosed Adult Patients with Ph-Negative Acute Lymphoblastic Leukemia in Adults up to Age 60: Results of a Multi-Center Phase II Clinical Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1629-1629 ◽  
Author(s):  
Jae H. Park ◽  
Ellen K. Ritchie ◽  
Arati V. Rao ◽  
Sean Devlin ◽  
Meier Hsu ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Enzymatic Activity ◽  
Phase Ii ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Hypersensitivity Reactions ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Background: The U.S. Intergroup C10403 trial has demonstrated that treating acute lymphoblastic leukemia (ALL) in adolescents and young adults up to age 39 using a pediatric regimen improves event-free and overall survival compared with adult regimens (Stock W et al. ASH 2014). However, the safety and efficacy in implementing pediatric regimens in older adults above age 40 have not been well studied. Herein, we report the results from a phase II multicenter study of pediatric-inspired regimen in newly diagnosed adult patients (pts) with ALL up to age 60 (NCT01920737). Methods: Newly diagnosed adult pts aged 18 to 60 with ALL were eligible. Burkitt type and Ph+ ALL were excluded. The treatment regimen consisted of induction 1 (I1), induction 2 (I2) followed by several cycles of intensifications and re-inductions and 3 years of maintenance therapy. The treatment contained a total of 6 doses of 2,000 IU/m2 pegylated asparaginase (Peg-ASP), administered IV at various intervals of ³4 weeks based on our previous pharmacokinetics (PK) data (Douer D et al. Blood 2007). Minimal residual disease (MRD) was assessed after I1 and I2 by multiparameter flow cytometry. Serum asparaginase enzymatic activity and presence of anti-asparaginase antibody (Ab) were assessed on day 7 after each Peg-ASP dose. Results: 27 pts were enrolled between 4/2014 and 4/2016. The median age at diagnosis was 43.6 (range, 20-60) years: 52% were 40-60 years. The majority had precursor B-ALL (70%) and rest T-ALL. Four pts (15%) had extramedullary disease only (mediastinal mass, lymph nodes, bone). Of the 27 pts, 26 pts (96%) achieved complete remission (CR) after I1. MRD was assessed in 20 pts; 8 (40%) and 15 (75%) pts achieved MRD neg CR after I1 and after I2, respectively. Six pts proceed to allogeneic HSCT. With a median follow-up of 7.8 months (range, 0.9-22.5), 3 patients (12%) relapsed: 2 occurred among the 12 MRD+CR group (17%) after I1 at 4.5 and 8.8 months, and 1 occurred among the 8 MRD negative CR group (13%) after I1 at 7 months from I1 completion. No relapses occurred among the 6 MRD unknown pts. No pt died on study. Grade 3-4 Peg-ASP-related toxicities (Table 1) included hypertriglyceridemia (59%), transaminitis (52%), hyperglycemia (41%), hyperbilirubinemia (30%), and pancreatitis (4%). Notably, all cases of hyperbilirubinemia occurred during I1 but despite continued use of Peg-ASP, grade 3-4 hyperbilirubinemia did not recur. Four pts (15%) developed hypersensitivity reactions to Peg-ASP and subsequently received Erwinia asparaginase without reaction and completed the full intended doses of Peg-Asp treatments. Three pts (11%) discontinued Peg-ASP due to toxicity (n=2; hyperbilirubinemia, transaminitis) and physician preference (n=1). Asparaginase PK and anti-ASP Ab data were available in 16 pts. In pts without hypersensitivity to Peg-ASP, a median asparaginase enzymatic activity was 0.58 IU/ml (range, 0.30-0.88) and 0.73 IU/ml (range, 0.53-0.88) on day 7 of Peg-ASP during I1 and I2, respectively. One pt developed silent inactivation after I1 with the activity level <0.01 IU/ml during I2 but without detectable anti-ASP Ab; 3 pts with hypersensitivity reactions had no or lowest activity levels, ranging from <0.01-0.1 IU/ml. Four pts (15%) had pre-existing anti-ASP Ab at pre-treatment; none of these was neutralizing and all 4 pts had adequate enzymatic activity. Conclusions: This phase 2 study suggests that a pediatric-inspired regimen containing rationally synchronized 6 doses of 2,000 IU/m2 IV Peg-ASP is safe and effective in older adults with newly diagnosed Ph-negative ALL up to age 60. Although follow-up remains short, we have observed high CR rates and few relapses. Hypertriglyceridemia, hyperglycemia, transaminitis and hyperbilirubinemia occurred frequently but few discontinued treatment due to toxicities. The rate of silent inactivation of asparaginase was low (6%), and almost all pts without hypersensitivity had adequate activity on day 7. Further results of asparaginase PK analysis and silent inactivation will inform the appropriate dosing of Peg-ASP and utility of PK/Ab tests in future adult ALL trials. Disclosures Park: Amgen: Consultancy; Genentech/Roche: Research Funding; Juno Therapeutics: Consultancy, Research Funding. Ritchie:Arian: Speakers Bureau; Novartis: Honoraria; Pfizer: Honoraria; Celgene: Speakers Bureau; Incyte: Speakers Bureau. Rao:Gilead Sciences: Employment, Equity Ownership. Douer:Jazz Pharmaceuticals: Honoraria; Gilled Sciences, Inc: Consultancy; Shire: Consultancy, Speakers Bureau; Pfizer: Consultancy; Spectrum: Consultancy.

scholarly journals Hypomethylating Agent and Venetoclax Combination Therapy Yields Superior Outcomes When Compared to Hypomethylating Agent Monotherapy in Patients ≥70 Years with Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1368-1368 ◽  
Author(s):  
Yumeng Zhang ◽  
Hannah H Asghari ◽  
Onyee Chan ◽  
Dasom Lee ◽  
Martine Extermann ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Response Rates ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Entire Cohort ◽  
Response Data

Background: Older patients with acute myeloid leukemia (AML) have inferior outcomes when compared to younger patients. Hypomethylating agents (HMA) were established as the standard of care for patients who are unfit for intensive induction chemotherapy until HMA and venetoclax (HMA+ven) combination approval by the FDA in December 2018. Approval of HMA+ven was based on an early phase study which produced high response rates; however, the combination was not compared head-to-head with HMA alone. A randomized phase 3 study is currently underway. There is no data available comparing HMA+ven to HMA monotherapy in older patients (age ≥70 years), thus we aimed to characterize responses in older patients when treated with these two regimens. Methods: We retrospectively reviewed clinical and molecular data on 225 patients at Moffitt Cancer Center and Memorial Health System with newly diagnosed AML who were ≥ 70 years old and were treated with HMA monotherapy or HMA+ven combination. Clinical data was abstracted in accordance with institutional review board approved protocol. Patients were then divided in two subgroups: Cohort A) HMA monotherapy and B) HMA+ven combination. We calculated overall response rates (ORR) defined as patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS). Fisher's Exact method was utilized to determine significance for categorical variables. All reported p-values are two sided. Next generation sequencing (NGS) results were analyzed using the TruSight Myeloid-54 gene panel with a sensitivity of 5%, and were characterized in patients treated in cohort B. Results: Among the 225 patients, 87% (n=196) were in cohort A and 13% (n=29) in cohort B. In cohort A, 36.7% were females compared to 27.6% in cohort B. Median age in both cohorts was 76 years (range: 70-90 years in cohort A) (range: 72-86 years in cohort B). Overall, 26% of the patients had adverse risk disease as defined by European Leukemia Net (ELN) classification in cohort A and 51.7% in cohort B. Baseline characteristics are described in Table 1. Overall response rate (ORR) of the entire cohort was 43.6% (n=92) (Table 2). ORR in cohort A was 25.5% (n=47) compared to 66.7% (n=18) in cohort B (p&lt;0.001). The median time to response in cohort A was 3.8 mos and was 1.9 mos in cohort B. Looking only at the 66 patients with ELN-defined adverse risk, response data were available in 62 patients, and the ORR in both cohorts was 25.8% (n=16), and was significantly lower in cohort A compared to B (14.9% vs. 60%, respectively, p=0.001) (Figure 1). Among the 136 patients with favorable or intermediate risk disease, response data were available in 127 patients, and the ORR was 35.4% (n=45). In cohort A the ORR in favorable/intermediate patients was 28.9% (n=37), and in cohort B it was significantly higher at 100% (n=8) (p&lt;0.001). Ten responding patients in cohort B had NGS data available at diagnosis and at the time of best response. Mutations cleared from the bone marrow in 60% (n=6) of these patients. With a median follow up of 11.7 months, the median overall survival (mOS) of the entire cohort was 15.03 months. The median follow-up time in cohort A is 46 months and in cohort B is 5.4 months, making assessment of relapse free survival or overall survival in cohort B premature. Early mortality rate was not different between the two cohorts (1.5% vs 3.4%, p=0.42). Conclusion: Our data provides convincing support that HMA+ven combination yields significantly higher response rates when compared to HMA monotherapy in newly diagnosed AML patients ≥70 years of age; an observation that is further strengthened by the short duration of follow-up in the HMA+Ven cohort. Responses are particularly striking in favorable and intermediate risk patients when treated with HMA+Ven. Overall our data supports the use of HMA+ven in the upfront setting for older patients with newly diagnosed AML. Additional follow-up in HMA+ven arm is needed to evaluate survival outcomes. Disclosures Kuykendall: Incyte: Honoraria, Speakers Bureau; Abbvie: Honoraria; Janssen: Consultancy; Celgene: Honoraria. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet:Agios, Biopath, Biosight, Boehringer Inglheim, Celator, Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm, Novartis: Consultancy; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Other: fees for non-CME/CE services . Komrokji:JAZZ: Speakers Bureau; Novartis: Speakers Bureau; JAZZ: Consultancy; Agios: Consultancy; Incyte: Consultancy; DSI: Consultancy; pfizer: Consultancy; celgene: Consultancy. Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Talati:Celgene: Honoraria; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria. Sweet:Pfizer: Consultancy; Incyte: Research Funding; Jazz: Speakers Bureau; Stemline: Consultancy; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Geriatric Assessment and Frailty Changes in Older Patients with Newly-Diagnosed Multiple Myeloma Undergoing Treatment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4774-4774 ◽  
Author(s):  
Hira S Mian ◽  
Gregory R Pond ◽  
Sascha A Tuchman ◽  
Mark A. Fiala ◽  
Tanya M. Wildes
Keyword(s):  
Mental Health ◽  
Physical Performance ◽  
Geriatric Assessment ◽  
Gait Speed ◽  
Older Patients ◽  
Research Funding ◽  
Well Being ◽  
Newly Diagnosed ◽  
Timed Up And Go

Introduction Multiple myeloma (MM) is a malignant plasma cell disease with a median age at diagnosis of 70 years. Geriatric assessment and frailty measures are increasingly being utilized at the time of diagnosis for prognostication. Gait speed at baseline has recently emerged as a powerful prognostic tool which identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers including myeloma (Liu et al, Blood 2019). However, the longitudinal assessment and responsiveness of change in geriatric assessment measures and functional frailty parameters, including physical performance such as gait speed, over time remains unknown. Objectives We conducted a prospective study of patients with newly diagnosed MM aged 65 and older at two institutions. The prevalence of geriatric domains at baseline has been previously published by Wildes et al (JAGS, 2019). We aimed to conduct a secondary analysis to understand the changes in geriatric and frailty assessment including physical performance as older patients underwent treatment for their myeloma. Methods Older patients with newly-diagnosed myeloma underwent a comprehensive geriatric assessment including a gait function using the Timed Up and Go test at baseline and at 6 months between the years 2012-2014. Results At baseline, forty patients were enrolled in the study with a mean age of 71.6 years; 25 (62.5%) were males. Thirty-six patients completed the 6-month follow-up with 18 patients having undergone a stem cell transplant in the interim. Overall, there were no significant change in the measured geriatric domains, including dependence, physical activity, falls, polypharmacy and cognition, at 6 months compared to baseline. Overall mental health well-being, measured with the Mental Health Inventory-17, improved over time (Table I). Physical performance, assessed with the Timed Up and Go test, showed a trend toward improvement as patients underwent treatment (11.0 seconds at the 6-month follow-up versus 12.3 at baseline, p=0.057). Additionally, two out of four individuals who were unable to complete the Timed Up and Go test at baseline were subsequently able to complete it 6 months following treatment. Conclusion Our study suggests that, for older patients with MM, treatment does not significantly lead to geriatric impairment at 6-months of follow-up, as compared to baseline and in fact is associated with improved overall mental health well-being. Additionally, both the incremental change in Timed Up and Go test and the number of individuals able to complete it may in fact improve as patients undergo treatment. This highlights that gait speed may not be static and improve with treatment, suggesting a dynamic model of frailty. Larger studies conducted longitudinally will be required to further evaluate these findings to explore the evolving concept of frailty in myeloma. Disclosures Mian: Amgen: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pond:Roche Canada: Employment, Other: Stock; Takeda (DSMC membership): Other: Honorarium. Tuchman:Alnylam: Honoraria, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; Karyopharm: Honoraria; Amgen: Research Funding; Sanofi: Research Funding; Merck: Research Funding; Prothena: Research Funding; Roche: Research Funding. Fiala:Incyte: Research Funding. Wildes:Janssen: Research Funding; Carvive: Consultancy.

Double disparities in patients with gastric cancer: Clinicopathology and survival of older adults in a Hispanic-rich population.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 169-169
Author(s):  
Madison H. Williams ◽  
Ryan A. Williams ◽  
Brian Hernandez ◽  
Joel Michalek ◽  
Sukeshi Patel Arora
Keyword(s):  
Gastric Cancer ◽  
Older Adults ◽  
Retrospective Analysis ◽  
Older Patients ◽  
Cancer Center ◽  
Younger Patients ◽  
Predominantly Hispanic ◽  
Significant Difference ◽  
Hispanic Patients

169 Background: Gastric cancer incidence increases with advancing age with a median age at diagnosis of 68. However, older adults (age ≥65) are underrepresented in clinical trials. Additionally, Hispanic populations have a higher incidence of gastric cancer compared with non-Hispanic patients and there is evidence that this population has worse outcomes. Given this double disparity in older Hispanic adults, we evaluated the differences in disease characteristics at diagnosis and survival outcomes in older adults compared to younger adults with gastric cancer at our South Texas cancer center serving a predominantly Hispanic population. Methods: We performed a retrospective analysis of patients with a diagnosis of gastric cancer from 2000 – 2018, who had follow-up at Mays Cancer Center, San Antonio, TX. Older patients were defined as ≥65 years and younger patients were defined as <65 years. Median overall survival (mOS) was estimated from Kaplan-Meier curves and groups were compared using the log-rank test. Results: A total of 190 patients met criteria for analysis. Patients were predominantly younger (age <65), with 128 (67.4%) young and 62 (32.6%) older. Most patients were Hispanic (66.4% of younger and 64.5% of older) and male (51.6% of younger and 66.1% of older). The majority of patients had an ECOG performance status of 0-2, including 61.7% and 64.5% (p = 0.55) of younger and older patients, respectively. At baseline, there was no significant difference in location of primary tumor, grade, stage at diagnosis, or histologic classification between younger and older patients (Table). There was also no significant difference between the two groups in H. pylori status, location of metastases, or HER2 status. Of the 109 patients with follow-up for survival, the mOS was 17 months (95% CI: 15-55) for younger patients versus 14 months (95% CI: 13-NR) for older patients (p = 0.19). Conclusions: In this retrospective analysis of predominantly Hispanic patients with gastric cancer, we found that there were no statistically significant differences in clinicopathologic features at diagnosis or in survival between younger versus older adults. Our study was approximately 2/3 Hispanic, a population for which there is a paucity of data, especially in older adults. Given the limited published research available to guide the management of older patients with gastric cancer, including Hispanics, further prospective real-world studies are needed to evaluate toxicity and quality of life in order to improve the care of older adults with gastric cancer. [Table: see text]

Quantitative Real-Time PCR of Peripheral Blood t(14;18) Positive Cells Predicts Treatment Response and Long-Term Outcome in Patients with Follicular Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 441-441
Author(s):  
Fabian Zohren ◽  
Ingmar Bruns ◽  
Juergen Barth ◽  
Sabrina Pechtel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Response ◽  
Peripheral Blood ◽  
Research Funding ◽  
Molecular Remission ◽  
Long Term Outcome ◽  
Free Survival ◽  
Significant Difference

Abstract Abstract 441 Introduction: By means of standard chemotherapy advanced stage follicular lymphoma (FL) is an incurable disease. Clinical courses are characterized by a continuous tendency to relapse caused by residual neoplastic cells. Quantitative polymerase chain reaction (qPCR) to detect lymphoma cell that carry the t(14;18) translocation is a suitable method to measure minimal residual disease (MRD) in patients with FL. Despite several reports dealing with MRD qPCR in FL, its role in the clinical management of patients is still not clearly defined. Therefore, we carried out a multicenter study, to assess the prognostic value of sequential quantitative MRD detection in first-line treatment of FL using an improved version of a LightCycler based qPCR specific for the major breakpoint region (MBR) positive IgH/bcl2 translocation, provided by Roche Diagnostics® (Penzberg Germany). Patients and Methods: We analysed 718 blood (PB) samples of 179 patients with newly diagnosed FL treated within the multicenter randomized trial NHL1, conducted by the German StiL group (Study group indolent Lymphomas), comparing 6 cycles of R–CHOP versus R–Bendamustin (R-B). Samples were taken at diagnosis, after 6 cycles of either R–CHOP or R–B immuno-chemotherapy and every three months during follow-up. All samples were analyzed in the department of Hematology at Heinrich-Heine University in Duesseldorf. Results: At diagnosis, 112 out of 179 patients (62.6%) were positive for IgH/bcl2 within the MBR in the peripheral blood. Significantly higher amounts of bcl2/IgH positive cells were found in patients with bone marrow infiltration (p=0.012) and depending on the number of lymphatic nodes (LN) with disease involvement (>3 LN p=0.003; >5 LN p=0.0009; >7 LN p=0.022). Overall, a remarkable inter-individual variation of bcl2/IgH positive cells in the PB at diagnosis, reflected by ratios from 0.000281 to 81, was found. The estimated event free survival (EFS) at 2 years of patients who presented at diagnosis low to normal amounts of bcl2/IgH positive cells in the PB (ratio < 2, n=83) was 82% (SE 0.045), which was significantly better than the 47% (SE 0.11) observed in patients showing the highest amount of bcl2/IgH positive cells (ratio >2, n=24) in the PB (p=0.003). By univariate and multivariate analysis, we found that the amount of bcl2/IgH positive cells in the PB at diagnosis (p=0.001) as well as the achievement of a negative MRD status after therapy (p=0.0001) were significant predictors for relapse free survival. Monitoring of MRD levels before and after therapy revealed that 6 cycles of immuno-chemotherapy significantly reduced the amount of bcl2/IgH positive cells in the PB compared with pre-treatment MRD levels (p=0.0001; median bcl2/IgH/tPA ratio: before treatment 0.0734, range: 0.000281–81, after treatment negative, range: negative–0.17). After treatment, 86% of the patients (n=82) achieved a molecular remission in the PB defined as qPCR negative, whereas 14% (13 patients) remained PCR positive. Not reaching a molecular remission in the PB at the end of therapy had a significant negative influence on PFS. After a median follow-up of two years, patients who remained MRD positive in the first measurement after therapy had a significant lower PFS than MRD negative patients (p=0.0001; 9 months vs. not reached). There was no significant difference in the degree of tumor cell depletion in the PB induced by the two different regimens. So far, 539 follow-up samples from 3 up to 39 months after therapy were analyzed. Patients with a consistent negative MRD status throughout follow-up showed a trend towards longer PFS. After 38 months follow-up, MRD positive patients had a PFS of 54% compared to 78% in the group of MRD negative patients (p=0.066). Conclusion: QPCR for the t(14;18) performed at diagnosis and during follow-up on PB samples predicts treatment response and long-term clinical outcome of patients with FL. Disclosures: Zohren: Roche: Honoraria, Research Funding. Rummel:Roche Pharma AG: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Amgen: Honoraria. Kobbe:Roche: Research Funding.

scholarly journals Haploidentical Transplant with Peripheral Blood Hematopoietic Cell Grafts in Older Adults with AML or MDS

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4658-4658
Author(s):  
Michael Slade ◽  
John F DiPersio ◽  
Peter Westervelt ◽  
Ravi Vij ◽  
Geoffrey L. Uy ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Research Funding ◽  
Disease Risk ◽  
Risk Index ◽  
Hematopoietic Cell ◽  
Comorbidity Index

Background: Modern post-transplant cyclophosphamide (PTCy) protocols with haploidentical (haplo) donors have dramatically expanded the donor pool for patients requiring hematopoietic cell transplantation (HCT). Initial studies were performed with bone marrow grafts, which require the donor to undergo anesthesia during harvest. Consequently, the use of mobilized peripheral blood hematopoietic cells (PBHC) may be desirable, especially with older donors. However, data on PBHC haplo-HCT in older adults is lacking. Objectives: To report the impact of age on transplant-related outcomes in a large cohort of patients undergoing haplo-HCT with PTCy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Methods: We retrospectively identified all adult patients undergoing T cell replete haplo-HCT with PTCy for AML or MDS at our institution from January 2009 to June 2016. Patients were grouped into three cohorts: Age1 (<55), Age2 (55-65) and Age3 (>65). Patients were scored for disease risk and underlying comorbidities using the Disease Risk Index (DRI) and HCT Comorbidity Index (HCT-CI). Overall survival (OS) was analyzed using a Cox Proportional Hazards (CPH) model, with all variables pre-specified. Results: We identified 107 patients, 92 with AML and 15 with MDS. Median follow up was 8.0 months in all patients and 18.3 months in patients surviving at last follow-up. Median donor age was 39, 34 and 49 in Age1, Age2 and Age3, respectively (p = 0.02). Donor relationship was also significantly different among Age1 (child: 25%, sibling: 53%, parent, 22%), Age2 (62%, 38%, 0%) and Age3 (64%, 36%, 0%) (p < 0.001). Younger patients were significantly more likely to receive myeloablative conditioning (55% vs. 35% vs. 27%, p = 0.04). Median OS was 448, 417 and 147 days in Age1, Age2 and Age3 patients. Actuarial 2-year OS was 40%, 34% and 11%, respectively. The 2-year cumulative incidence of relapse was 34%, 30% and 56%. The 2-year cumulative incidence of treatment-related mortality was 30%, 45% and 35%. There was a trend towards a lower 100-day cumulative incidence grade II-IV acute graft-versus host-disease (aGVHD) in older patients (44% vs. 35% vs. 15%, p = 0.07) but not in grade III-IV aGVHD (16% vs. 7% vs. 5%, p = 0.42). Similarly, there was a trend towards a lower 1-year cumulative incidence of cGVHD in older patients (37% vs. 36% vs. 10%, p = 0.07), but not severe cGVHD (5% vs. 0% vs. 0%, p = 0.16). No significant difference was seen in median time to neutrophil engraftment (17 vs. 18 vs. 17 days, p = 0.14) or platelet engraftment (28 vs. 30.5 vs. 32 days, p = 0.93). Univariate and multivariate CPH model of OS is summarized in table 1. Age > 65 and prior allogeneic HCT were associated with significantly worse survival. Conclusions: The use of PBHC haplo-HCT in older adults with AML or MDS is a feasible treatment option. However, a careful pre-transplant evaluation and analysis of risks and benefits is warranted when offering this transplant modality to older adults. Even after adjusting for pre-transplant comorbidity and disease risk, older age is associated with inferior survival in this cohort. Cox Proportional Hazard Analysis of Overall Survival. Abbreviations: Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), Disease Risk Index (DRI) Figure 1 Overall survival by age Figure 1. Overall survival by age Disclosures DiPersio: Incyte Corporation: Research Funding. Vij:Takeda: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Consultancy; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Karyopharm: Honoraria. Schroeder:Incyte Corporation: Honoraria, Research Funding.

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