Age-adjusted International Prognostic Score Research Articles

Outcomes of very elderly patients with aggressive B-cell non-Hodgkin lymphoma treated with reduced-dose chemotherapy.

Although the number of patients aged 80years or older with aggressive B-cell non-Hodgkin lymphoma (B-NHL) has increased in the clinical setting, management has been challenging due to lower tolerability. The aim of the present study was to evaluate the efficacy and safety of reduced-dose chemotherapy for very elderly patients. We retrospectively analyzed the clinical outcomes of patients aged ≥80years old with diffuse large B-cell lymphoma (n=58) or grade 3 follicular lymphoma (n=3). Patient ages ranged from 80 to 93years old, with a median of 83years old. Twenty-four patients were treated with CHOP or THP-COP, the dosages of which were variably reduced, in combination with rituximab (R-vCHOP), while another 24 patients were treated with R-miniCHOP. Twelve R-vCHOP and 16 R-miniCHOP patients completed the chemotherapy cycles. The estimated 2-year progression-free and overall survival rates in the R-vCHOP and R-miniCHOP groups were 53 and 39% (P=0.92) and 53 and 48% (P=0.95), respectively. Performance status ≥2, lactate dehydrogenase level >normal, serum albumin ≤3.5g/dL, C-reactive protein ≥2.0mg/dL, age-adjusted International Prognostic Score 2/3, and withdrawal from the chemotherapy cycle were associated with poor survival. The frequency of chemotherapy-related hospitalization during the second or later cycles was significantly less in the R-miniCHOP group. The efficacies of R-vCHOP and R-miniCHOP were similar in patients aged ≥80years old with aggressive B-NHL. The reduced frequency of hospitalization observed for R-miniCHOP treatment is beneficial for very elderly patients.

Clinical Study Of Dose-Adjusted EPOCH Regimen For Non-Hodgkin's Lymphoma With Hemophagocytic Lymphohistiocytosis: Preliminary Results Of An Ongoing Phase II Study

▪ IntroductionHemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS) is characterized by cytokines storm and uncontrolled activation of macrophages. Secondary HLH in adults may occur in different occasions, including infections, autoimmune diseases, carcinomas and hematologic malignancies, in which Lymphoma-associated hemophagocytic lymphohistiocytosis(LA-HLH) has a high fatality rate and the worst outcome. The major cause of LA-HLH is aggressive non-Hodgkin's lymphoma (NHL), especially T/NKT cell lymphomas. Until now, there is no recommended therapeutic schedule for this fatal disease. Because of promising results of etoposide-containing regimen for HLH and high effective of continuous infusion chemotherapy regimen for aggressive NHL .The investigators therefore employed an intensive chemotherapy regimen--DA-EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) to treat non-Hodgkin's lymphoma with hemophagocytic lymphohistiocytosis and we have performed a preliminary analysis of this ongoing Phase 2 study and evaluated safety and efficacy of this regimen. MethodsThe clinical trial was designed as a prospective, multicenter, single-arm phase 2 clinical trial (NCT01818908). Enrolled patients included those with previously untreated NHL, and met the diagnostic criteria of either HLH2004 or ASH 2009 of HLH, patients with primary HLH and secondary HLH other than NHL were excluded. Therapeutic protocol of DA-EPOCH regimen was as follows: etoposide 50 mg/m2 CI 24h d1-d4, doxorubicin 10 mg/m2 CI 24h d1-d4, vincristine 0.4 mg/m2 CI 24h d1-d4, cyclophosphamide 750 mg/m2 IV d5, prednisone 60 mg/m2 oral d1-d5, If enrolled patient was histologically confirmed CD20+ B cell lymphoma, standard dose of rituximab will be recommended to combine with DA-EPOCH regimen. Drug dose was adjusted as previously described (Wyndham H. et al, 2002), each cycle of treatment was administered every 21 to 28 days according to recovery of toxicities. For patients who responded to the treatment and did not have disease progression, interim evaluation was conducted after 3 cycles of treatment. ResultsAt the time of analysis 26 patients were enrolled and 20 patients were eligible to evaluate. Patients were 60.0% (12/20) male with median age 44(range: 14-60), the age-adjusted international prognostic score (aaIPI) enrolled to study was high/intermediate (2 score) 10/20, high risk group (3 score) 10/20. Histologies were four B-NHL, ten T-NHL and six NK-NHL. The median number of cycles of therapy was 3, patients who had discontinued study were mainly due to rapid disease progression. The overall response rate (ORR) among treated pts was 50.0%, with 35.0% (7/20) of patients achieving CR/CRu and 15.0% (3/20) achieving PR, and 50.0% of patients (10/20) had PD. With the median follow-up of 8 months, progression-free survival (PFS) rate was 46.3% and in subgroup analysis, PFS of B-NHL, T-NHL and NK-NHL was 75%, 45.7% and 25% respectively (Fig. 1); Overall survival (OS) rate was 52.4%(Fig. 2) and 75.0%, 58.3%, 22.2% in subgroup of B-NHL, T-NHL and NK-NHL(Fig. 3). The most common grade ≥3 treatment-related side effects were hematologic toxicities including neutropenia and thrombocytopenia. [Display omitted] [Display omitted] [Display omitted] ConclusionsLymphoma-associated hemophagocytic lymphohistiocytosis progresses rapidly and has a high mortality rate, our preliminary results suggest DA-EPOCH regimen has acceptable toxicities and promising activity in NHL with HLH, especially for B-NHL and T-NHL, but prognosis of NK-NHL with HLH remains dismal, urgent need for novel therapeutic strategies may benefit the survival of patients with this disease. Disclosures:No relevant conflicts of interest to declare.

High Response Rate with Favorable Survival Projections in High-Risk Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Receiving R-CHOP-14 or Early Intensified Chemotherapy with Rituximab and Autograft (R-HDS): Results of the Interim Analysis of A GITIL Prospective Multicenter Phase III Study.

Abstract 1220Poster Board I-242 BackgroundThe outcome of B-cell diffuse large B-cell lymphoma (DLB-CL) patients has definitely improved since the introduction of therapeutic programs combining chemotherapy and the anti CD20 rituximab. However, the outcome of patients with adverse prognostic factors still needs a substantial improvement and intensive therapy with autologous stem cell transplantation (ASCT) may represent a feasible option. In a previous Phase II study the combination of rituximab and high-dose (HD) sequential chemotherapy, delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS regimen), proved effective and well tolerated in previously untreated patients with DLB-CL and age-adjusted International Prognostic Score (aaIPI) score 2-3 (Tarella et al.: Leukemia 2007). Based on this study, a multicenter Phase III study was planned to compare the R-HDS regimen to a standard dose dense, rituximab supplemented R-CHOP-14 chemotherapy program. Patients and MethodsThe multicenter phase III trial R-HDS 0305 (Clinical Trials.gov.number NCT00355199) was planned to include 240 patients with DLBCL without CNS with stage '2 II B, bulk, age 18-60 years, with ECOG-PS=0-3 and aaIPI 2-3 or age 61-65 years with ECOG-PS=0-2 and IPI 3-5. The control group received 8 courses of R-CHOP-14, supported by GCSF ± involved field radiotherapy (IFRT), if they achieved at least a PR after 4 cycles. Cases refractory to R-CHOP-14 were rescued with R-HDS. Experimental arm (RHDS) included: 3 courses of doxorubicin-containing chemotherapy (APO), followed by sequential administration of cyclophosphamide (CTX) 7 g/sqm, Cytarabine (Ara-C) 2g/sqm every 12 hours for 6 days, etoposide 2 g/sqm plus cisplatin 100 mg/sqm; the program was completed by mitoxantrone plus melphalan (60 and 180 mg/sqm) or BEAM conditioning regimen with ASCT± IFRT. Rituximab (375 mg/sqm) was given for a total of 6 doses, twice after CTX and Ara-C, as in vivo purging before CD 34+ cells harvest, and twice after ASCT. The primary outcomes of the study were CR, DFS, OS, EFS and toxicity. From June 2005 to February 2009, 165 patients were enrolled in the study (R-CHOP-14=83; RHDS=82). The planned interim analysis has been carried out on 119 patients who have been randomized up to March 2008. ResultsThe median age was 49 years (range, 18-65), 11 patients (9.2%) were> 60 years and the M/F was 1.38. Patients in two arms presented with comparable adverse features such as advanced stage (87%), BM infiltration (24%), bulky disease (67%), elevated LDH (81%) and beta 2-microglobulin (mean 3.9 mg/dl, SD = 4.5), poor ECOG-PS (60%), B-symptoms (62%), and ≥1 extranodal site (63%). Until now 10 patients (8%) did not complete the planned program because of toxicity or PD, 6 and 4 cases, respectively. One patient resistant to R-CHOP-14 was shifted to R-HDS. Overall, 24 patients (20%) deceased during the course of the study, 20 (17%) died from lymphoma, 2 (2%) due to therapy complications and 2 (2%) from hepatitis B reactivation. Moreover, 6 patients (5%) recovered from severe adverse events: 1 interstitial pneumonia, 1 graft failure, 1 sepsis, 1 colon diverticulitis, 1 shock, 1 prolonged aplasia. The main G>2 hematological toxicity were: anemia, granulocytopenia and thrombocytopenia, in 42%, 60 % and 45 % of patients, respectively. Grade >2 gastrointestinal, hepatic and infectious toxicity were recorded in 32 %, 11 % and 20% of patients, respectively.One-hundred and eight of 119 patients (91%) were alive and assessable for the response rate and clinical outcome at final restaging. Eighty-nine patients (82%) achieved CR, 8 PR and 7 had SD or PD. With a median follow up of 18.1 months (SD= 9.3, range 0.3–40.6 months) the 2year OS, DFS and EFS of the 119 evaluable patients are 80%, 84% and 74%, respectively. ConclusionThis interim analysis shows that in high-risk DLBCL patients aged =/<65 years, R-CHOP 14 and R-HDS with ASCT: i. are feasible therapeutic strategies with an acceptable risk profile; ii. induces an overall high response rate, markedly superior to historical results reported for high-risk aggressive lymphoma. The favorable survival projections allow to continue the study protocol until its planned conclusion in order to verify any possible difference between R-CHOP14 and R-HDS in terms of therapeutic efficacy. DisclosuresNo relevant conflicts of interest to declare.

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.