Comparison of clinical scoring systems in aggressive B-cell lymphomas (BCL): An individual patient-level analysis across international trials (SEAL).

7544 Background: Great heterogeneity in survival exists for patients (pts) newly diagnosed with aggressive BCL. Three scoring systems based on simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the international prognostic index (IPI), revised-IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We studied BCL pts treated with R-CHOP to determine which scoring systems best identifies subgroups with poor outcomes that might benefit from new approaches. Methods: Individual pt data from 7 multicenter trials (1998-2009) of pts with BCL (86% DLBCL) treated front-line with R-CHOP (or variant) were analyzed to determine whether IPI, R-IPI, or NCCN-IPI best discriminated overall survival (OS). The concordance index (c-index) from a proportional hazards model, stratifying on trial and induction therapy, quantified predictive accuracy of each scoring system. Results: 2561 pts (median age 63 yrs, 56% male) were classified into IPI, R-IPI, and NCCN-IPI risk groups (Table). With a median follow-up of 5 yrs, NCCN-IPI had the greatest absolute difference in OS estimates between the highest and lowest risk groups at 1, 3, and 5 yrs, and best discriminated OS (c-index = 0.631, Table). Conclusions: In an independent and large cohort of pts, NCCN-IPI performs best in risk-stratifying pts with aggressive BCL, readily distinguishing pts at high and low risk for treatment failure using clinical parameters (5-yr OS between 48 and 92%). Improvement over the simpler IPI appears incremental, and IPI may remain a valuable alternative. Work integrating molecular features of the tumor into the (NCCN-) IPI is in progress to define high risk groups where targeted novel approaches are needed most. [Table: see text]

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First-line chemotherapy plus cetuximab in patients grouped according to prognostic risk factors: Analysis of the CRYSTAL and OPUS studies.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3591 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3591-3591

Author(s):

Gunnar Folprecht ◽

Eric Van Cutsem ◽

Carsten Bokemeyer ◽

Michael Schlichting ◽

Steffen Heeger ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Performance Status ◽

Risk Groups ◽

Rank Test ◽

Clinical Parameters ◽

First Line ◽

Ecog Performance Status ◽

Hazards Model ◽

Line Chemotherapy

3591 Background: Analysis of randomized trials has shown that mCRC patients (pts) can be divided into prognostic risk groups according to baseline clinical parameters including ECOG performance status, white blood cell count (WBC), alkaline phosphatase (ALP) and number of metastatic (met) sites (Köhne C, et al. Ann Oncol 2002;13:308-17). The effect of adding cetuximab to first-line chemotherapy (CT) on overall survival (OS) in these groups of KRAS wild-type mCRC pts was investigated in the CRYSTAL and OPUS studies. Methods: Pt risk groups were: low-risk (LRG= ECOG 0/1, 1 met site) intermediate-risk (IRG= ECOG <1, >1 met site, ALP <300 U/L or, ECOG>1, low WBC, 1 met site) and high-risk (HRG= ECOG<1, >1 met site, ALP>300 U/L or ECOG>1, high WBC, or ECOG>1, low WBC and >2 met sites). Exploratory analyses comprised estimates of effects using Cox‘s proportional hazards model for OS on individual pt data and comparison of treatment arms by log-rank test. Results: Data are shown in the table. In the pooled analyses, in both treatment arms OS was longest in LRG pts and shortest in HRG pts. Adding cetuximab to CT led to marked improvements in OS in the HRG (Hazard ratio [HR] 0.765, 95% CI 0.506–1.157, p=0.203) and IRG (HR 0.781, 95% CI 0.622–0.981, p=0.033), while improvements in LRG pts (HR 0.869, 95% CI 0.672–1.124, p=0.287) were observed only after prolonged follow up. Data were similar in the separate CRYSTAL and OPUS studies. Conclusions: The analysis confirms the concept of prognostic risk groups for OS according to baseline clinical parameters in pts with KRAS wt mCRC. Benefit from the addition of cetuximab to first-line CT in terms of OS appears to be more pronounced in the IRG and HRG. [Table: see text]

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A New Prognostic Index (MIPI) for Patients with Advanced Stage Mantle Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.814.814 ◽

2006 ◽

Vol 108 (11) ◽

pp. 814-814 ◽

Cited By ~ 1

Author(s):

Eva Hoster ◽

Martin Dreyling ◽

Michael Unterhalt ◽

Joerg Hasford ◽

Wolfgang Hiddemann

Keyword(s):

Prognostic Factors ◽

Performance Status ◽

International Prognostic Index ◽

External Validation ◽

Prognostic Index ◽

Risk Groups ◽

Intermediate Risk ◽

Advanced Stage ◽

Ecog Performance Status ◽

Wbc Count

Abstract On behalf of the German Low Grade Lymphoma Study Group (GLSG) and the European MCL Network. Background: There is no generally established prognostic classification system for patients with mantle cell lymphoma (MCL), as the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) have been developed based on data of patients with diffuse large cell and follicular lymphoma, respectively. Methods: The data of 455 patients with advanced stage MCL treated first-line within three clinical trials of GLSG and European MCL Network have been analyzed to clarify the prognostic relevance of IPI and FLIPI and to derive a new prognostic index of overall survival (OS). Age, sex, ECOG performance status, Ann Arbor stage, B-symptoms, number of extranodal sites, number of involved nodal areas, tumor size, serum LDH activity, WBC count, platelet count, hemoglobin, albumin, β2-microglobulin and cell proliferation (Ki-67) were considered as candidate prognostic factors. Statistical methods included Kaplan-Meier estimates and logrank test for the validation of IPI and FLIPI and multiple Cox regression with backward variable selection for the derivation of the new prognostic index. Results: IPI showed a significant impact on OS, but low-intermediate and high-intermediate risk groups comprised more than two thirds of the patients and were not well separated. According to the FLIPI, only 6% of the patients were classified as low risk and almost two thirds of the patients as high risk, and low and intermediate risk groups were not separated. Four of the candidate prognostic factors were independently associated with OS, namely age, ECOG performance status, LDH and WBC count. The relative risk was 1.42 (95% confidence interval 1.18 to 1.72, p = 0.0002) for an increased age by ten years, 2.01 (1.19 to 3.39, p = 0.0088) for an ECOG greater than one, 1.51 (1.13 to 2.02, p = 0.0059) for a 2 fold elevation of LDH and 2.56 (1.66 to 3.95, p < 0.0001) for a 10 fold increase of WBC count. According to these four parameters, patients could be classified into a low risk (44% of the patients, median OS not reached), an intermediate risk (35%, median OS 51 months), and a high risk group (21%, median OS 29 months). Discussion: IPI and FLIPI showed only modest prognostic discrimination in our external validation data set of patients with advanced stage MCL. In contrast, age, ECOG performance status, LDH and WBC were identified as independent prognostic factors of OS, and three reasonably sized and well separated risk groups were defined. With four clinical prognostic factors readily determined in clinical routine, our new prognostic index (MIPI) is superior to the IPI. Bootstrap validation confirmed the separation of three risk groups, but external validation is still needed. The MIPI may prove to be an important tool to facilitate risk-adapted treatment decisions for patients with advanced stage MCL.

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The Significance of Serum Albumin Level and Platelet Count in Patients with Diffuse Large B-Cell Lymphoma in the Context of an Enhanced International Prognostic Index (NCCN-IPI)

Blood ◽

10.1182/blood.v126.23.1463.1463 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1463-1463 ◽

Cited By ~ 1

Author(s):

Yotaro Ochi ◽

Yusuke Koba ◽

Yoshimitsu Shimomura ◽

Yuichiro Ono ◽

Nobuhiro Hiramoto ◽

...

Keyword(s):

Platelet Count ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

The Elderly ◽

Prognostic Impact ◽

Five Factors ◽

Group 2

Abstract Introduction The International Prognostic Index (IPI) is used to predict survival in patients with diffuse large B-cell lymphoma (DLBCL). The IPI includes five factors: age, stage, LDH, performance status, and extranodal sites. However, studies suggest that certain blood markers not included in the IPI, such as CRP, albumin, absolute lymphocyte count (ALC), and platelet count, predict survival. Recently, an enhanced IPI (NCCN-IPI) was proposed and showed excellent prognostic performance. It uses the same factors as the IPI, but refines the impact of age and LDH and the definition of extranodal disease. Few studies have assessed the prognostic impact of blood markers other than the five factors of the IPI in the context of the NCCN-IPI. Here, we analyzed the prognostic role of simple blood markers in the NCCN-IPI. Patients and Methods Data from consecutive DLBCL patients diagnosed between January 2004 and June 2014 were retrospectively analyzed. Patients receiving rituximab and anthracycline-based chemotherapy were included in the analysis. Values considered positive were CRP >1 mg/dl, albumin <3.5 g/dl, ALC <1,000/µl, or platelets <100,000/µl. The primary endpoint was overall survival (OS), assessed using the Kaplan-Meier method. The log-rank test and Cox regression analysis were used to assess the prognostic value of each variable. Results A total of 398 patients (median age, 69 years (range, 21-104)) were included. Of these, 124 (31.2%) had an ECOG performance status >1, 221 (55.5%) had advanced stage disease, and 223 (56.1%) had a high or high-intermediate NCCN-IPI score (>3). Pretreatment CRP, albumin, ALC, and platelet count values were positive in 215 (54%), 127 (31.9%), 144 (36.2%), and 31 (7.8%), respectively. The median follow-up was 34.8 months (range, 0.5-134) and the 5-year OS of the entire cohort was 68.8%. Univariate analysis identified CRP [hazard ratio (HR) 3.15; 95% confidence interval (CI) 2.07-4.80, p<0.001), albumin (HR 4.46; 95% CI 2.96-6.7, p<0.001), ALC (HR 2.40; 95% CI 1.62-3.54, p<0.001), platelet count (HR 4.69; 95% CI 2.87-7.67, p<0.001), and NCCN-IPI score >3 (HR 5.05; 95% CI 3.00-8.51, p<0.001) as significant for OS. NCCN-IPI, albumin, and platelet count remained significant in multivariate analysis (NCCN-IPI: HR 3.14; 95% CI 1.77-5.60, p<0.001; albumin: HR 2.41; 95% CI 1.36-4.27, p=0.002; platelets: HR 2.77; 95% CI 1.66-4.61, p<0.001), whereas CRP and ALC did not (CRP: HR 0.91; 95% CI 0.51-1.66, p=0.78; ALC: HR 1.33; 95% CI 0.87-2.03, p=0.18). Based on albumin and platelet count values, patients were divided into three risk groups for OS: group 1 included albumin- and platelet-negative patients (n=247); group 2 included either albumin- or platelet-positive patients (n=128); and group 3 included both albumin- and platelet-positive patients (n=23) (82.6%, 50.2% and 12.9%, respectively; p<0.001) (Figure 1A). The association of these risk groups with OS independently of the NCCN-IPI was evaluated. For patients with low or low-intermediate NCCN-IPI, the 5-year OS for group 1 (n=151), group 2 (n=22), and group 3 (n=2) was 89.2%, 76.8%, and 0%, respectively (p<0.001) (Figure 1B). For patients with high or high-intermediate NCCN-IPI, the 5-year OS for groups 1 (n=96), 2 (n=106), and 3 (n=21) was 72.6%, 44.3%, and 14.6%, respectively (p<0.001) (Figure 1C). Assessment of the prognostic impact of albumin and platelet count in the elderly led to the exclusion of the low risk category (score 0-1) among those older than 60 years (n=291) because of their age score points (>1 points) in the NCCN-IPI; thus, the ability of NCCN-IPI to differentiate risk groups might be diminished in the elderly. For low-intermediate (n=97), high-intermediate (n=118), and high (n=76) NCCN-IPI patients, the 5-year OS for the elderly according to the NCCN-IPI was 80.3%, 64.8% and 42.5%, respectively (p<0.001) (Figure 2A). The combination of albumin and platelet count also predicted survival in the elderly: the 5-year OS for groups 1 (n=169), 2 (n=103), and 3 (n=19) was 77.7%, 50.1%, and 0%, respectively (p< 0.001) (Figure 2B). Conclusion Despite the improved performance of the NCCN-IPI, albumin and platelet count were independent prognostic factors and predicted survival even in the elderly. Considering albumin and platelets may improve the accuracy of recently established prognostic models. Prospective studies should evaluate the prognostic impact of albumin and platelets. Disclosures No relevant conflicts of interest to declare.

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A New Prognostic Index In Diffuse Large B-Cell Lymphoma Using Serum Albumin: A Pilot Study Evaluating The Albumin Adjusted-International Prognostic Index (A-IPI)

Blood ◽

10.1182/blood.v122.21.4267.4267 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4267-4267 ◽

Cited By ~ 1

Author(s):

Samir Dalia ◽

Julio C Chavez ◽

Celeste M. Bello ◽

Paul A. Chervenick ◽

Bryan J Little ◽

...

Keyword(s):

Cell Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

Ecog Performance Status ◽

Large B Cell Lymphoma ◽

Disease Biology ◽

Ann Arbor

Abstract Introduction Low serum albumin (SA) has been identified as a prognostic marker in multiple hematological malignancies including diffuse large B-cell lymphoma (DLBCL). Low SA may be an indicator of worsening disease biology, increased inflammation, or increased co-morbidities. Changing demographics and improved care of the elderly may abrogate some of the risk attributable to age. SA, however, may not be influenced by such changes. Currently the Revised International Prognostic Index (R-IPI), the currently best accepted model for prognosis in DLBCL, does not account for albumin. We therefore explored the use of albumin as a prognostic variable in conjunction with the covariates included in the R-IPI. Methods Patients with DLBCL treated between 2007-2010 with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) were retrospectively identified using the Moffitt Total Cancer Care platform. Age, ECOG performance status, LDH, extrandoal sites of disease, stage, and albumin were collected and analyzed using Random Forest Modeling. Both age and extranodal involvement failed to retain statistical significance and were dropped from the model, leading to the generation of a new algorithm, the Albumin Adjusted IPI (A-IPI). This score assigned a point for SA<3.7g/dL, LDH >the upper limit of normal, ECOG performance status >=2, and Ann Arbor stage III-IV. Progression free and overall survival was compared by the risk groups using Kaplan-Meier curves along with the log rank test. Statistical analysis was done using R statistical software. Results A total of 124 patients were identified. Median age was 58 years with 62% male. 46% were over the age of 60 at diagnosis and 63% were Ann Arbor stage 3 or 4. The A-IPI score identified three groups of patients (Very good: A-IPI=0, Good: A-IPI=1-2, Poor: A-IPI=3-4), similar to the R-IPI. PFS and OS at 4 years were compared using the A-IPI and R-IPI (Table 1). Conclusions In comparison to the R-IPI, the A-IPI appears to better define poor risk patients while retaining the ability to discriminate well between low (“Very Good”) and intermediate (“Good”) risk groups. Confirmation in a larger and prospective cohort is indicated, however, these preliminary data suggest SA may be a better surrogate for co-morbid status, pro-inflammatory states, and worse disease biology than age in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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Association of the Lung Immune Prognostic Index with Immunotherapy Outcomes in Mismatch Repair Deficient Tumors

Cancers ◽

10.3390/cancers13153776 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3776

Author(s):

Edouard Auclin ◽

Perrine Vuagnat ◽

Cristina Smolenschi ◽

Julien Taieb ◽

Jorge Adeva ◽

...

Keyword(s):

Checkpoint Inhibitors ◽

Performance Status ◽

Prognostic Index ◽

Predictive Marker ◽

Risk Groups ◽

Two Factors ◽

One Year ◽

Metastatic Sites ◽

Tumor Types

Background: MSI-H/dMMR is considered the first predictive marker of efficacy for immune checkpoint inhibitors (ICIs). However, around 39% of cases are refractory and additional biomarkers are needed. We explored the prognostic value of pretreatment LIPI in MSI-H/dMMR patients treated with ICIs, including identification of fast-progressors. Methods: A multicenter retrospective study of patients with metastatic MSI-H/dMMR tumors treated with ICIs between April 2014 and May 2019 was performed. LIPI was calculated based on dNLR > 3 and LDH > upper limit of normal. LIPI groups were good (zero factors), intermediate (one factor) and poor (two factors). The primary endpoint was overall survival (OS), including the fast-progressor rate (OS < 3 months). Results: A total of 151 patients were analyzed, mainly female (59%), with median age 64 years, performance status (PS) 0 (42%), and sporadic dMMR status (68%). ICIs were administered as first or second-line for 59%. The most frequent tumor types were gastrointestinal (66%) and gynecologic (22%). LIPI groups were good (47%), intermediate (43%), and poor (10%). The median follow-up was 32 months. One-year OS rates were 81.0%, 67.1%, and 21.4% for good, intermediate, and poor-risk groups (p <0.0001). After adjustment for tumor site, metastatic sites and PS, LIPI remained independently associated with OS (HR, poor-LIPI: 3.50, 95%CI: 1.46–8.40, p = 0.02. Overall, the fast-progressor rate was 16.0%, and 35.7% with poor-LIPI vs. 7.5% in the good-LIPI group (p = 0.02). Conclusions: LIPI identifies dMMR patients who do not benefit from ICI treatment, particularly fast-progressors. LIPI should be included as a stratification factor for future trials.

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Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma

Blood Cancer Journal ◽

10.1038/s41408-020-00394-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alessia Castellino ◽

Aung M. Tun ◽

Yucai Wang ◽

Thomas M. Habermann ◽

Rebecca L. King ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

Local Therapy ◽

Progression Free Survival ◽

Cell Transplant ◽

Multiple Lesions ◽

Mantle Cell

AbstractPrimary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes.

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Randomized Comparison of ACVBP and m-BACOD in the Treatment of Patients With Low-Risk Aggressive Lymphoma: The LNH87-1 Study

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.6.1309 ◽

2000 ◽

Vol 18 (6) ◽

pp. 1309-1315 ◽

Cited By ~ 44

Author(s):

Hervé Tilly ◽

Nicolas Mounier ◽

Pierre Lederlin ◽

Josette Brière ◽

Brigitte Dupriez ◽

...

Keyword(s):

Group Performance ◽

Remission Rate ◽

Performance Status ◽

International Prognostic Index ◽

Eastern Cooperative Oncology Group ◽

Prognostic Index ◽

Tumor Burden ◽

Low Risk ◽

Aggressive Lymphoma ◽

Standard Regimen

PURPOSE: To compare a short intensified regimen followed by sequential consolidation therapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone [ACVBP]) to the standard regimen of methotrexate, bleomycin, cyclophosphamide, and etoposide (m-BACOD) in patients with low-risk aggressive lymphoma. PATIENTS AND METHODS: A total of 752 patients with intermediate- or high-grade lymphoma and no adverse prognostic factors (Eastern Cooperative Oncology Group performance status of 2 to 4, ≥ two extranodal sites of disease, tumor burden ≥ 10 cm in largest dimension, bone marrow or CNS involvement, Burkitt’s or lymphoblastic subtypes) were registered. Of 673 eligible patients, 332 received ACVBP and 341 received m-BACOD. RESULTS: The complete remission rate was identical (86%) in the two groups. With a median follow-up duration of 7 years, the 5-year failure-free survival (FFS) rate was 65% in the ACVBP group and 61% in the m-BACOD group (P = .16). The 5-year overall survival rate was 75% in the ACVBP group and 73% in the m-BACOD group (P = .47). ACVBP was responsible for more severe and life-threatening infections (P < .01), but m-BACOD caused more pulmonary toxicity (P < .001). The number of treatment-related deaths did not differ between the two regimens. A multivariate analysis indicated that ACVBP was associated with a longer FFS in patients with two or three risk factors of the International Prognostic Index. CONCLUSION: In this population of patients with low-risk aggressive lymphoma, toxicities of the regimens are different, but the rates of response and survival are identical. The survival advantage of ACVBP over standard regimen in patients with advanced disease is suggested by this analysis but remains to be assessed in prospective studies specifically designed for this purpose.

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First-MIND: A phase Ib, open-label, randomized study to assess safety of tafasitamab (tafa) or tafa + lenalidomide (LEN) in addition to R-CHOP in patients with newly diagnosed DLBCL.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7540 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7540-7540

Author(s):

David Belada ◽

Katerina Kopeckova ◽

Juan Miguel Bergua ◽

Marc André ◽

Ernesto Perez Persona ◽

...

Keyword(s):

Performance Status ◽

Randomized Study ◽

International Prognostic Index ◽

Prognostic Index ◽

Dose Intensity ◽

Newly Diagnosed ◽

Open Label ◽

Bulky Disease ◽

Phase Ib ◽

Ecog Ps

7540 Background: Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity and phagocytosis. It is FDA-approved with LEN for adult patients (pts) with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation. First-MIND (NCT04134936) is a Phase Ib, open-label, randomized study of tafa + R-CHOP or tafa + LEN + R-CHOP in newly diagnosed DLBCL. Methods: Eligible pts were ≥18 years, treatment-naïve, with histologically confirmed DLBCL not otherwise specified, international prognostic index (IPI) 2–5 and ECOG performance status (PS) 0–2. Pts with known double- or triple-hit and transformed lymphoma were excluded. Treatment (Tx) comprised six 21-day cycles of tafa (12 mg/kg IV, Day [D] 1, 8, 15) + R-CHOP (arm A) or tafa (12 mg/kg IV, D1, 8, 15) + LEN (25 mg orally, D1–10) + R-CHOP (arm B). G-CSF and VTE prophylaxis was mandatory. Primary objective is safety; secondary objectives are ORR, PET-CR rate at end of Tx, PFS, long-term safety, pharmacokinetics, immunogenicity. Results: From Dec 2019 to Aug 2020, 83 pts were screened in Europe and the US; 66 were randomized (33 per arm). Data cut-off for this analysis: 9 Dec 2020; study is ongoing. Median age was 64.5 years (range 20–86). Overall, 30% (20/66) of pts were ≥70 years and many had high-risk disease: IPI 2 29%, IPI 3 46%, IPI 4 26%. ECOG PS: 47% of pts were ECOG PS 0, 44% PS 1, 9% PS 2. Most pts had stage III/IV disease (92%); 46% had bulky disease. All pts experienced a treatment-emergent adverse event (TEAE). Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and 12.1% (arm A) and 66.7% and 30.3% (arm B) of pts, respectively (Table). Serious TEAEs occurred in 42.4% (arm A) and 51.5% (arm B) of pts. There were three deaths, unrelated to tafa and/or LEN (sepsis, urosepsis, and COVID-19 pneumonia). R-CHOP dose intensity was maintained in both arms. Among 60 pts who completed tumor assessments after cycle 3, ORR was 89.7% (arm A) and 93.5% (arm B). Conclusions: These data suggest R-CHOP + tafa or tafa + LEN is tolerable in pts with Tx-naïve DLBCL and that R-CHOP dosing is not affected. Toxicities are similar to those expected with R-CHOP or R-CHOP + LEN. Updated safety and early efficacy data will be presented at the conference. Clinical trial information: NCT04134936. [Table: see text]

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International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades

Blood ◽

10.1182/blood.v86.4.1460.bloodjournal8641460 ◽

1995 ◽

Vol 86 (4) ◽

pp. 1460-1463 ◽

Cited By ~ 99

Author(s):

J Hermans ◽

AD Krol ◽

K van Groningen ◽

PM Kluin ◽

JC Kluin-Nelemans ◽

...

Keyword(s):

Clinical Trial ◽

Hodgkin’S Lymphoma ◽

Performance Status ◽

International Prognostic Index ◽

Prognostic Index ◽

Population Based ◽

Hodgkin's Lymphoma ◽

Intermediate Grade ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

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Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma: an Eastern Cooperative Oncology Group trial (E3493)

Blood ◽

10.1182/blood.v100.5.1634.h81702001634_1634_1640 ◽

2002 ◽

Vol 100 (5) ◽

pp. 1634-1640 ◽

Cited By ~ 18

Author(s):

Joseph A. Sparano ◽

Edie Weller ◽

Tipu Nazeer ◽

Thomas Habermann ◽

Ann E. Traynor ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

International Prognostic Index ◽

Eastern Cooperative Oncology Group ◽

Prognostic Index ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Intermediate Grade ◽

Non Hodgkin Lymphoma

Preclinical and clinical evidence suggest a potential advantage for infusional therapy in lymphoma. Sixty-two analyzable patients with predominantly intermediate-grade non-Hodgkin lymphoma received cyclophosphamide (200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2per day) (CDE) by continuous intravenous infusion for 4 days (96 hours) every 3 weeks for a maximum of 8 cycles. By the age-adjusted International Prognostic Index (IPI), 42% were at high risk and 58% were at high-intermediate risk. Complete response (CR) occurred in 30 (48%) patients (95% confidence interval [CI], 35%, 64%), and partial response occurred in 16 (26%) patients, yielding an overall response rate of 74% (95% CI, 62%, 84%). Failure-free survival (FFS) rates at 1 and 2 years were 55% (95% CI, 43%, 67%) and 50% (95% CI, 38%, 62%), respectively. When comparing the outcome for 62 patients receiving infusional CDE with historical data derived from 927 IPI-matched lymphoma patients using a Cox proportional hazards model, there was a nonsignificant trend favoring CDE in FFS (P = .12) and overall survival (P = .09). Severe or life-threatening toxicity included neutropenia (68%), anemia (57%), thrombocytopenia (44%), and infection (24%). Two patients (3%) died of treatment-related infectious complications. The primary end point of improving 1-year FFS from 55% to 70% was not achieved with infusional CDE given as initial therapy in patients with poor-risk intermediate-grade lymphoma. It is unlikely that infusional therapy as used in this study produces a 25% or greater relative improvement in FFS compared with standard therapy.

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