Retrospective Study of the Utility of Follicular Lymphoma International Prognostic Index (FLIPI) and FLIPI2 In Patients with Follicular Lymphoma Uniformly Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, and Prednisone

Abstract Abstract 3100 The Follicular Lymphoma International Prognostic Index (FLIPI) is the most useful prognostic index for follicular lymphoma (FL). FLIPI was developed from retrospective data, which was based on treatment without rituximab (R) therapy and did not contain β2-microglobulin data of some cases. Recently the working group that had suggested FLIPI proposed FLIPI2, based on prospectively collected data. However, FLIPI2 contains data on several different treatment methods, such as treatment with or without R therapy. The present study aimed to retrospectively analyze the prognosis of FL uniformly treated with the combination of R, cyclophosphamide, doxorubicin, vincristin, and prednisone (R-CHOP). This study involved 114 patients consecutively diagnosed with FL who were treated with R-CHOP and were registered in the data-base of the Yokohama City University Hematology Group between January 2001 and October 2009. All the parameters required for FLIPI and FLIPI2 calculation were present in 108 patients (men, 53; women, 55, median age; 57 years [34- 78 years]). The median follow-up period was 31.7 months (0.8- 97.5 months). According to the FLIPI score, 50 patients (46.3%) were in the high-risk group (HR); 31 patients (28.7%), the intermediate-risk group (IR); and 27 patients (25.0%), the low-risk group (LR). On the basis of the FLIPI2 score, 45 patients (41.7%) were in HR; 52 patients (48.1%), IR; and 11 patients (10.2%), LR. According to FLIPI, the 5-year overall survival (5yOS) was 74.1% (95% CI, 58.1– 94.4%) for HR, 89.5% (95%, CI, 76.6– 100%) for IR, and 100% for LR (p = 0.0049); the 5-year time to failure (5yTTF) was 42.3% (95% CI, 26.0– 68.9%) for HR, 39.1% (95% CI, 22.7– 67.3%) for IR, 66.4% (95% CI, 47.2– 93.4%) for LR (p = 0.244). According to the FLIPI2 score, 5yOS was 71.3% (95% CI, 53.2– 95.6%) for HR, 85.6 % (95% CI, 72.0– 100%) for IR, and 100% for LR (p = 0.197), the 5yTTF was 35.8% (95% CI, 20.0– 64.2%) for HR, 46.7% (95% CI, 31.1– 70.3%) for IR, and 76.2% (95% CI, 52.1– 100%) for LR (p = 0.075). In conclusion, in FL patients treated with R-CHOP, FLIPI provided a more accurate OS than that provided by FLIPI2; however, FLIPI2 provided a more accurate TTF than that provided by FLIPI. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Clinical Prognostic Models in Diffuse Large B-Cell Lymphoma Patients Are Still Essential in the Rituximab Era

Blood ◽

10.1182/blood.v124.21.3057.3057 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3057-3057

Author(s):

Luis Alberto de Padua Covas Lage ◽

Renata Oliveira Costa ◽

Abrahão Elias Hallack Neto ◽

Sheila Siqueira ◽

Rodrigo Santucci ◽

...

Keyword(s):

High Risk ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

High Risk Group ◽

Intermediate Risk ◽

Risk Patients ◽

Risk Categories

Abstract Introduction: To evaluate a new enhanced IPI proposed by the National Comprehensive Cancer Network (NCCN-IPI) in DLBCL patients, we compared the international prognostic index (IPI), R-IPI and NCCN-IPI in DLBCL patients treated with rituximab, cyclophosphamide, hidroxydaunorubicin, vincristine and prednisone (R-CHOP). Methods: From June 2008 to November 2011 we retrospectively evaluated 146 DLBCL patients treated with R-CHOP-21 referred for cancer treatment in a single university institution in Brazil. Patient's clinical data were assessed to calculate the IPI, R-IPI and NCCN-IPI. Results: Patient's median age was 58.9 years (range 16 – 86); 85 (57.8%) were female. According to IPI, risk categories were low (n=41, 28.1%), low-intermediate (n=43, 29.5%), high-intermediate (n=37, 25.3%) and high (n=25, 17.1%). Using R-IPI, risk categories were very good (n=19, 13%), good (n=65, 44.5%) and poor (n=62, 42.5%). According to NCCN-IPI, risk categories were low (n=12, 8.2%), low-intermediate (n=52, 35.6%), high-intermediate (n=62, 42.5%) and high (n=20, 13.7%). At 30 months (median follow up 17.7 months - range 0.6-58.2 months) the overall survival (OS) was 75.5%. The progression-free survival (PFS) at a median follow-up of 16.3 months (range 0.6-52.4) was 68.3% for all patients. Using IPI, the OS at 30 months did not differ between low and low-intermediate risk patients (96.8% vs. 82.2%; p=0.136); however, it was higher than the OS of high-intermediate risk (n=37; 96.8% vs 74.1% p=0.11) and high-risk (n=25; 96.8% vs 41% p < 0.001) patients (Figure 1). The NCCN-IPI demonstrated significant differences in OS (p < 0,001) and PFS (p<0.001) among low-intermediate, high-intermediate, and high risk groups, with the high-risk group exhibiting worse OS (32.1% in 30 months) (Figure 2). According to IPI, the OS in high-risk patients was 41%. Figure 1: OS and PFS according to International Prognostic Index (IPI) Figure 1:. OS and PFS according to International Prognostic Index (IPI) Figure 2: OS and PFS according to NCCN-IPI Figure 2:. OS and PFS according to NCCN-IPI Figure 3 Figure 3. Conclusion: In our study the NCCN-IPI, but not the IPI or R-IPI was able to discriminate a high-risk group of DLBCL patients treated with R-CHOP with worse OS. Disclosures No relevant conflicts of interest to declare.

Download Full-text

The Follicular Lymphoma International Prognostic Index (FLIPI) Predicts Treatment Outcome in Patients with Advanced Stage Follicular Lymphoma Treated Front-Line with Rituximab and the Combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP).

Blood ◽

10.1182/blood.v106.11.925.925 ◽

2005 ◽

Vol 106 (11) ◽

pp. 925-925 ◽

Cited By ~ 1

Author(s):

Christian Buske ◽

Eva Hoster ◽

Martin Dreyling ◽

Joerg Hasford ◽

Michael Unterhalt ◽

...

Keyword(s):

Treatment Outcome ◽

Relative Risk ◽

High Risk ◽

Follicular Lymphoma ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Intermediate Risk ◽

Advanced Stage ◽

Front Line

Abstract Background: The Follicular Lymphoma International Prognostic Index (FLIPI) has been developed to predict prognosis and to allow risk adapted treatment decisions in patients with follicular lymphoma (FL) before the widely use of Rituximab. However, the addition of Rituximab to standard induction chemotherapy with its long-term beneficial effects has profoundly changed the treatment outcome in patients with advanced stage FL and has become the new standard in the first line therapy of this disease. Therefore, we addressed the question, whether the prognostic value of the FLIPI could be reconfirmed in patients with advanced stage FL treated initially with a rituximab/chemotherapy combination. Methods: The FLIPI index was tested in patients treated with Rituximab and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone, R-CHOP) in a prospective multicenter phase 3 trial of the GLSG using the time to treatment failure (TTF) as target parameter. Results: 362 Patients treated with R-CHOP were evaluable for TTF. Of the 338 patients evaluable for all FLIPI risk factors, 14% of patients were classified as low, 41% as intermediate and 45% as high risk. After a median follow-up time of 20 months, patients with low risk and intermediate risk FLIPI had almost identical TTF (2-years TTF 92% vs 90%, 95% C.I., 83% to 100% and 84% to 96%, respectively). In contrast, the TTF was significantly shorter in the high risk FLIPI group (2-years TTF 67%, 95% C.I., 58% to 76%) as compared to the combined low/intermediate risk FLIPI group (relative risk 3.0, 95% C.I., 1.7 to 5.1; p < 0.0001). In addition, responding patients with high risk FLIPI had a significantly shorter progression free survival as compared to the low/intermediate risk group (relative risk 3.3, 95% C.I., 1.8 to 6.0; p < 0.0001). When postremission treatment was taken into account, the FLIPI separated the high risk group from the low/intermediate risk group in 65 patients treated with autologous stem cell transplantation (relative risk 6.0, 95% C.I., 1.4 to 25.2) as well as in 242 patients who had received IFN-α maintenance or no postremission therapy (relative risk 3.2, 95% C.I., 1.8 to 5.8). As the FLIPI was able to separate the high from the low/intermediate risk group in patients with advanced follicular lymphoma treated initially with Rituximab and CHOP we next performed a multivariate analysis to determine the impact of the individual parameters incorporated in the FLIPI on the TTF. The serum LDH level greater than the upper normal limit (relative risk 2.6, 95% C.I., 1.5 to 4.5) and the hemoglobin level below 12 g/dl (relative risk 2.5, 95% C.I., 1.4 to 4.3) were independently associated with a shorter TTF in these patients, whereas the age and the number of nodal areas were not discriminant. Conclusion: Taken together, these data indicate that the FLIPI is a valid prognostic index for identifying high-risk patients in FL, also after front-line combined immuno-chemotherapy. The index will remain an important tool to adjust treatment decisions in individual patients according their risk profile and to design clinical trials for the different risk groups in the era of antibody-based therapy.

Download Full-text

Neither the FLIPI Nor the FLIPI2 Accurately Segregates Low- Risk From Intermediate- Risk Follicular Lymphoma Patients in Terms of Progression-Free Survival

Blood ◽

10.1182/blood.v118.21.2663.2663 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2663-2663

Author(s):

Inas El-Najjar ◽

Janet Matthews ◽

John Gribben ◽

Silvia Montoto

Keyword(s):

Follicular Lymphoma ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Free Survival ◽

Study Population

Abstract Abstract 2663 Background: Follicular Lymphoma International Prognostic Index (FLIPI) is the most frequently used prognostic index for risk stratification in follicular lymphoma (FL) patients. The FLIPI was designed retrospectively in the pre-rituximab era, with overall survival (OS) as the end-point. Follicular Lymphoma International Prognostic Index 2 (FLIPI2) is a more recent index designed prospectively in the rituximab era to overcome these drawbacks. Aim: To compare the efficacy of the FLIPI and FLIPI2 prognostic indexes in discriminating patients with FL with a distinct outcome in terms of OS and progression-free survival (PFS). Patients: From 1985 to 2007, 302 patients were newly diagnosed with grade 1–3a FL in our institution. The FLIPI could be retrospectively assigned in 220 patients and the FLIPI2 in 149 patients. The 122 patients (47 male/75 female; median age: 56 years –range: 25–87) in whom both the FLIPI and FLIPI2 indexes were assessable constitute the study population. Seventy-five patients (61%) received treatment immediately after diagnosis (of which, 25 patients received rituximab containing regimens), whereas the remainder were managed expectantly. Main characteristics at diagnosis are as follows: age>60 years, 41%; stage III-IV, 70%; Hb<12 g/L, 17%; bone marrow involvement, 45%; largest lymph node diameter>6cm, 26%; B2M>ULN, 20% and LDH>ULN, 17%. The median follow-up for alive patients was 86 months (range: 12– 270). Results: Five-year OS and PFS were 74% (95%CI: 69–79) and 38% (95%CI: 32–44), respectively, for the 302 patients. There were no significant differences in the outcome of these patients in comparison with the 122 patients comprising the study population. The distribution of the 122 patients according to the FLIPI and FLIPI2 as well as the 5-year OS and 5-year PFS are shown in the table. The FLIPI and the FLIPI2 indexes predicted OS (p<0.0001 both for the FLIPI and the FLIPI2), but the FLIPI2 did not accurately separate patients with low-risk from those with intermediate risk in terms of OS (p=0.3). The FLIPI score predicted PFS (p=0.001) but was not able to discriminate patients with low-risk from those with intermediate-risk (p=0.6). There was a trend for the FLIPI2 to predict PFS (p=0.06) but it did not segregate the low-risk group from the intermediate-risk group (p=0.3) Conclusions: The FLIPI separates patients into 3 risk groups, well-balanced in terms of the proportion of patients in each group with a distinct OS. In contrast the, majority of the patients fall into the intermediate risk group according to the FLIPI2, and overlaps with the low risk group in terms of OS. With regards to PFS, both indexes are poor at separating low and intermediate risk groups. In summary, both indexes are good at defining a relatively small high-risk population but do not accurately segregate the rest. FLIPI2 does not appear to be superior to FLIPI for risk stratification. This supports that the future lies in uncovering biological factors that might help in the guidance of treatment, in addition to segregating patients more accurately into specific risk groups. Disclosures: Gribben: Roche: Honoraria; Genentech: Honoraria; GSK: Honoraria; Muundipharma: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.

Download Full-text

Prognostic Factors in Follicular Lymphoma Patients in Japan: Application of Follicular Lymphoma International Prognostic Index.

Blood ◽

10.1182/blood.v106.11.4702.4702 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4702-4702

Author(s):

Chizuko Hashimoto ◽

Heiwa Kanamori ◽

Naoto Tomita ◽

Shin Fujisawa ◽

Etsuko Yamazaki ◽

...

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

Response Rate ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

High Risk Group ◽

Prognostic Models ◽

Appropriate Treatment ◽

New Treatment

Abstract Background: By the new treatment approaches, such as anti-CD20 monoclonal antibody, purine analogues, high-dose therapy with SCT, the outcome of treatment for follicular lymphoma (FL) has been improved, but there is no consensus on any of these approaches except cases with early stage. Therefore, a reliable prognostic index would be needed in order to select the most appropriate treatment. Follicular Lymphoma International Prognostic Index (FLIPI) has recently been reported. We assessed characteristics at diagnosis and applied two prognostic models, the FLIPI and the IPI, to newly diagnosed Japanese patients (pts) with FL in this study. Methods: Response rate, overall survival (OS), and progression free survival (PFS) were calculated by the FLIPI and the IPI. For two prognostic models, 5 factors were used, The IPI (age>60, EN≥2, LDH>N, PS≥2, CS≥3), and the FLIPI (age>60, Hb<12.0g/dl, LDH>N, CS≥3, nodal sites>4), respectively. Results: Between 1988 and 2001, 107 pts of newly diagnosed FL (grade I-III) were analyzed. Patients characteristics were male/female 49/58, median age 54yr. (range 21–87yr.), and histological grade I, II/III 103/4. Initial therapy was CHOP-like regimen for 56 patients, ACOMP-B (the third generation regimen) for 44 patients, and another for 7 patients. The median follow-up of our series was 84 months (range 40–206 mo.). CR, PR was 60.7%, 31.8%, and response rate was 92.5%. Median OS at 15 years was 64.4%, and median PFS at 15 years was 28.5%. Patient distribution by the IPI and the FLIPI were the followings; the IPI (L/LI/HI/H 49/41/15/2), the FLIPI (L/I/H 41/29/37). There were few patients equivalent to high risk group in IPI, and it was the patient distribution which was more equal in FLIPI in comparison with IPI. OS by the IPI and the FLIPI risk group at 10 year were L: 85%, LI: 54%, HI: 44%, H: 50% (p=0.0088), and L: 87%, I: 66%, H: 47% (p<0.0001). PFS by the IPI and the FLIPI risk group at 10 year were L: 36%, LI: 23%, HI: 27%, H: 0% (p=0.0679), and L: 43%, I: 25%, H: 16% (p=0.0003). Correlation with a survival was recognized in FLIPI on OS, PFS more by significantly. In high-risk group of the FLIPI, PFS was significantly longer in pts treated with ACOMP-B, compared with pts treated with CHOP-like regimen (p=0.0015), and it tended to be better in OS, not so significant. Conclusions: The FLIPI is a promising consequence prediction model in follicular lymphoma in Japan. Standard treatment of FL is one of the most controversial issues. Outcome of CHOP were poor in high-risk group of the FLIPI, so to improve survival new treatment strategy is needed. The therapeutic strategy on the basis of different risks by reliable prognostic index, such as the FLIPI is necessary in future, in order to select the most appropriate treatment. As for grade 3, there was a little number of patients in our series, but further examination is necessary for adaptation of the FLIPI about this group.

Download Full-text

Nongastric Marginal Zone B-Cell Lymphoma: A Prognostic Model from a Retrospective Multicenter Study.

Blood ◽

10.1182/blood.v110.11.1361.1361 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1361-1361

Author(s):

Sung Yong Oh ◽

Hyuk-Chan Kwon ◽

Won Seog Kim ◽

Yeon Hee Park ◽

Kihyun Kim ◽

...

Keyword(s):

B Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

High Risk Group ◽

Intermediate Risk

Abstract Purpose: The International Prognostic Index (IPI) and Follicular Lymphoma Prognostic Index (FLIPI) are used as prognostic indices for NHL and indolent lymphoma. However, marginal zone B-cell Lymphoma (MZL) evidences a distinctive clinical presentation and a natural course; thus, in this study, we attempted to devise an adequate prognostic index for MZL. Patients and method: From 1990 to 2005, 205 patients diagnosed with MZL were retrospectively reviewed. After analysis of the prognostic factors, progression free survival (PFS) and overall survival (OS), we constructed a prognostic index of MZL (MZLPI) via the summation of each factor. We then compared PFS and OS with IPI, FLIPI, and MZLPI. Results: According to our multivariate analysis of PFS and OS of MZL, nodal MZL, ECOG performance ≥ 2 and advanced stage were composed of MZLPI. MZLPI was grouped as follows: score 0 as a low risk group, score 1 as an intermediate risk group, and score ≥2 as a high risk group. The PFS curve, according to MZLPI results, evidenced a more discriminated pattern than IPI and FLIPI, and this was especially true in the intermediate risk group. In OS, MZLPI (P=0.0007) evidenced a more discriminated pattern than IPI (P=NS) or FLIPI (P=0.0044). Conclusion: MZLPI, which is constructed of relatively simple factors, may represent a useful prognostic index for the prediction of PFS and OS in MZL, and may also be used as a substitute for IPI or FLIPI.

Download Full-text

Is the International Prognostic INDEX for CLL (CLL-IPI) Useful to Predict Time to First Treatment of Patients with EARLY Disease? Results of a Prospective Multicenter Analysis

Blood ◽

10.1182/blood.v126.23.498.498 ◽

2015 ◽

Vol 126 (23) ◽

pp. 498-498 ◽

Cited By ~ 1

Author(s):

Stefano Molica ◽

Diana Giannarelli ◽

Luciano Levato ◽

Rosanna Mirabelli ◽

Massimo Gentile ◽

...

Keyword(s):

High Risk ◽

Conflicts Of Interest ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

Low Risk ◽

Intermediate Risk ◽

Early Disease ◽

Binet Stage ◽

Time To First Treatment

Abstract BACKGROUND: The CLL-IPI score is a large cooperative effort in which clinical data collected from 8 randomized trials were used to develop an internationally applicable prognostic index for CLL patients. The model includes 5 independent parameters that predict for overall survival such as age, clinical stage, del(17p) and/or TP53 mutation, IGHV mutation status and β2-microglobulin (B2M) level. A potential limitation for an extensive use of CLL-IPI is represented, however, by the fact that only 20% of patients included in the full analysis set had early disease. PATIENTS: The present analysis based on an observational multicenter CLL database including 337 Binet stage A patients (O-CLL1 protocol, clinicaltrial.gov identifier NCT00917540) was designed to assess the utility of the CLL-IPI score to predict time to first treatment (TTFT) in patients with early disease. RESULTS: Patients were followed up for a total of 2038 person-years (median, 42 months; range, 1-82 months), during which 91 (26.9%) experienced disease-progression requiring therapy according to 1996 IWCLL guidelines. The CLL-IPI score enabled Binet stage A patients to be divided into three subgroups [i.e., score 0-1, low-risk (n=229); score 2-3, intermediate-risk(n=99); score 4 or higher, high-risk (n=9)] that differed with respect to TTFT (P<0.0001). A comparative performance analysis between CLL-IPI and 2007 MD Anderson Cancer Center (MDACC) score, barely based on traditional clinical parameters (i.e., age, gender, Rai substage, absolute lymphocyte count, number of involved nodal groups and B2M), revealed that prediction of the TTFT was more accurate with the former. The c-statistic of the MDACC model was 0.62 (95% CI: 0.49-0.75) a level below than that of the CLL-IPI (c=0.70; 95% CI:0.58-0.81) and below the accepted 0.7 threshold necessary to have value at the individual patient level. These results are in keeping with the change in area under the receiver operating characteristic (ROC) curve (AUC) which increased from 0.646 (95% CI: 0.578-0.714) to 0.720 (95%CI:0.658-0.783) when moving from MDACC model to CLL-IPI score. Since the CLL-IPI score was originally derived from patients with active CLL enrolled in phase 3 trials we sought for different cut-off scores that better predict for TTFT in our patient cohort of early CLL. According to the recursive partitioning (RPART) analysis, a classification tree was built that identified three subsets of patients who scored 0 (low- risk,n=139), 1(intermediate-risk, n=90) and >1 (high-risk, n=108), respectively. The probability of remaining free from therapy at 5 years was 85% in the low-risk group, 68% in the intermediate-risk group and 47% in the high-risk group (P<0.0001)(Fig 1). Our revised IPI score remained a predictor of TTFT also when analysis was limited to 262 Rai stage 0 (P<0.0001) and 99 clinical monoclonal B-cell lymphocytosis (cMBL) cases (P=0.006). CONCLUSIONS: The results of this study confirm the utility of CLL-IPI score for predicting TTFT in a prospective cohort of community-based patients with early CLL at presentation. Our effort to adapt CLL-IPI score to patients with early disease meets the need to separate Binet stage A patients into different prognostic groups suitable for individualized follow-up programmes and possibly for early therapeutic interventions. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Pre-Enucleation Chemotherapy in Advanced Intraocular Retinoblastoma. Central America Follow Up: AHOPCA II

Journal of Global Oncology ◽

10.1200/jgo.2016.004440 ◽

2016 ◽

Vol 2 (3_suppl) ◽

pp. 75s-75s

Author(s):

Sandra Luna-Fineman ◽

Soad L. Alabi ◽

Mauricio E. Castellanos ◽

Yessika Gamboa ◽

Ligia Fu ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Central America ◽

Conflicts Of Interest ◽

Risk Group ◽

High Risk Group ◽

Globe Rupture ◽

Neo Adjuvant Chemotherapy ◽

Standard Risk

Abstract 57a Purpose: A significant percentage of patients in Central America present with buphthalmos, carrying a high risk of globe rupture and orbital contamination. In 2007, AHOPCA introduced chemotherapy before enucleation in children with buphthalmos. Methods: Patients with advanced intraocular disease were considered standard-risk and underwent enucleation. Those with diffuse invasion of choroid, postlaminar optic nerve, or anterior chamber invasion received 4-6 cycles of adjuvant chemotherapy (vincristine, carboplatin, etoposide). Patients with buphthalmos or perceived to be at risk for abandonment were considered high-risk, given 2-3 cycles of chemotherapy before enucleation to compete 6 cycles regardless of pathology. All cases were discussed via online meetings. Results: From 2007 to 2014, 396 patients were enrolled; 240 had IRSS stage I (174 unilateral). 143 had upfront enucleation, 95 had pre-enucleation chemotherapy, 1 is pending enucleation and 1 abandoned before enucleation. The standard-risk group 69 had risk pathology and 76 had no risk factors; 125 had no events, 5 abandoned 11 relapsed/progressed and 2 died of toxicity. Of 95 high-risk group, 8 abandoned, 20 relapse/progressive, 6 had toxic deaths and 61 are alive at last follow-up (median time of 4 years). Of high risk group, 55 were unilateral, 82% are alive. At 7 years OS (abandonment-censored) was 95±0.02 and 79±0.04 for standard-risk and high-risk (p=0.008). Conclusion: AHOPCA addressed advanced intraocular disease with an innovative approach. In eyes with buphthalmos and patients with risk of abandonment, neo-adjuvant chemotherapy is effective, when followed by post-enucleation chemotherapy. This approach avoids ocular rupture and intensified therapy, and reduces refusal/abandonment rate. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.

Download Full-text

R-FND Followed by Radioimmunotherapy for High-Risk Follicular Lymphoma

Blood ◽

10.1182/blood.v112.11.3056.3056 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3056-3056 ◽

Cited By ~ 7

Author(s):

Peter McLaughlin ◽

Sattva Neelapu ◽

Michelle Fanale ◽

Maria Rodriguez ◽

Ana Ayala ◽

...

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Ibritumomab Tiuxetan ◽

Free Survival ◽

Grade 3 ◽

Anti Cd20 ◽

Better Than

Abstract Follicular lymphoma (FL) patients, (pts) with high-risk features using the FL International Prognostic Index (FLIPI) have an expected 5-year survival of only about 50% with conventional therapy. With the incorporation of anti-CD20 monoclonal antibody (mAb) therapy, results are improving (e.g., Buske, Blood2006; 108: 1504). Starting in 2003, we have treated high-risk (FLIPI ≥3) FL pts with R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) for 4 cycles, followed by radioimmunotherapy (RIT) with ibritumomab tiuxetan, and subsequent rituximab maintenance. Results for the first 35 pts are: complete (CR) and partial (PR) remission 83% and 14%; 3-year overall (OS) and failure-free survival (FFS) 89% and 74% (median follow-up 24 mo.). RIT converted 5 PR pts to CR. Toxicity was mainly hematologic. Five pts did not receive RIT, one because of neutropenia after R-FND. Following RIT, platelet and neutrophil nadirs were 28 and 0.3, occurring at 4–7 weeks. 16 pts required transfusions, and 27 received growth factors. 13 pts had infections, only 2 of which were grade 3. Recovery occurred by 3 weeks in most, with prolonged cytopenias in 6. There has been 1 case of myelodysplasia. In conclusion, the additional complexity of this RIT intensification strategy is warranted in this high-risk FL population, resulting in OS and FFS outcomes that are better than non-mAb therapies, and at least as good as published chemotherapy-rituximab combination therapy.

Download Full-text

Risk Adjusted Management of Newly Diagnosed High and Intermediate FLIPI Follicular Lymphoma Using (90)Y Ibritumomab Tiuxetan

Blood ◽

10.1182/blood.v128.22.1794.1794 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1794-1794

Author(s):

Neil L Berinstein ◽

Nancy M Pennell ◽

Rashmi Weerasinghe ◽

Matthew C. Cheung ◽

Eugenia Piliotis ◽

...

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

B Cell ◽

International Prognostic Index ◽

Prognostic Index ◽

Newly Diagnosed ◽

Ibritumomab Tiuxetan ◽

Cell Counts ◽

Post Therapy

Abstract Background: Although the natural history of follicular lymphoma is indolent with a median overall survival of about 12-15 years, the disease is heterogeneous. The 5 and 10 year overall survival (OS) of low, intermediate and high risk FLIPI is 91%, 78% and 53% and 71%, 51% and 36% using standard rituximab-based treatment. 5-year progression-free survival (PFS) is 80%, 70% and 48% respectively. Methods: Based upon this we conducted an investigator-initiated single-centre Phase II trial of intensified therapy with CHOP-R followed by (90)Y ibritumomab tiuxetan consolidation and 24 months of rituximab maintenance as treatment for patients with intermediate and high-risk newly diagnosed symptomatic follicular lymphoma. 33 patients were enrolled. Results: The addition of (90)Y ibritumomab tiuxetan was well tolerated but resulted in asymptomatic grade 3 or 4 thrombocytopenia and neutropenia in11-36% and 10-24% of patients between weeks 2-8 post (90) Y. After 9 years of follow-up (median follow-up 61 months) the 0S for intermediate and high risk FLIPI was 95% and 78%. The 5 year PFS was 79% and 64% for intermediate and high risk FLIPI, respectively. Responses at three months post consolidation were as follows: 3/33 (9%) achieved CR, 25/33(76%), achieved CRU, 1/33(3%) had PR, and 1/33(3%) had PD. Three patients did not receive (90)Y ibritumomab tiuxetan due to disease progression 2/33(6%), or death 1/33(3%). Of 19 patients who had a molecular marker for their lymphoma, 18 (95%) achieved molecular remissions in peripheral blood with CHOP-R therapy. Nine (47%) of these patients have been recently assessed for MRD and remain in molecular remission. The therapy resulted in decreased levels of IgG, IgM and IgA below the lower normal level in 33%, 40% and 23% of patients respectively post therapy. These levels did not recover in most of these patients. B cells were depleted to undetectable levels during therapy including rituximab maintenance. In 18 evaluable patients only 11 recovered normal B cell counts post maintenance rituximab. There was no correlation between normal B-cell recovery and Ig levels. Many patients with low or no B cell counts had normal IgG levels, whereas some patients who regained normal B cell counts were still unable to reach normal Ig levels. No patient developed human anti-mouse antibody. Immunity to measles, mumps, or rubella was retained post therapy. Patients did not have significant infections or opportunistic infections (although 2 developed Grade 1 shingles post (90)Y ibritumomab tiuxetan) and none required IVIG. Conclusions: We conclude that this intensified regimen is highly active in cyto-reducing lymphoma in high and intermediate risk FLIPI follicular lymphoma patients. The toxicity is tolerable although a significant percentage of patients will end up with persistent asymptomatic reductions in B cells and serum Ig. Only randomized trials will determine whether this regimen enhances outcome over standard of care in this higher risk follicular lymphoma population. References: 1.Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices. Nooka AK, Nabhan C, Zhou X, Taylor MD, Byrtek M, Miller TP, Friedberg JW, Zelenetz AD, Link BK, Cerhan JR, Dillon H, Sinha R, Shenoy PJ, Levy D, Dawson K, Hirata JH, Flowers CR. Ann Oncol. 2013 Feb;24(2):441-8. doi: 10.1093/annonc/mds429. Epub 2012 Oct 5 2.Validation, revision and extension of the Follicular Lymphoma International Prognostic Index (FLIPI) in a population-based setting. van de Schans SA, Steyerberg EW, Nijziel MR, Creemers GJ, Janssen-Heijnen ML, van Spronsen DJ. Ann Oncol. 2009 Oct;20(10):1697-702. doi: 10.1093/annonc/mdp053. Epub 2009 Jun 23. PMID: 19549712 Disclosures Buckstein: Novartis: Honoraria; Celgene: Honoraria, Research Funding.

Download Full-text

Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.534.534 ◽

2016 ◽

Vol 128 (22) ◽

pp. 534-534

Author(s):

Natasha Catherine Edwin ◽

Jesse Keller ◽

Suhong Luo ◽

Kenneth R Carson ◽

Brian F. Gage ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Discriminative Ability ◽

Blood Institute ◽

C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

Download Full-text