Outcomes of Follicular Lymphoma Patients By Dynamic FLIPI at Diagnosis and Initial Treatment in the Post-Rituximab Era

Abstract Background: Prognosis of follicular lymphoma (FL) has long been defined by the FLIPI score (Solal-Céligny et al., 2004) which is a 5 factor risk model consisting of age, stage, lactate dehydrogenase, hemoglobin and number of nodal areas. The FLIPI model has been validated at diagnosis in both the pre- and post-Rituximab eras. However, many patients are initially observed and have prolonged lead time from diagnosis to first treatment. In this study, we investigated whether FLIPI risk group at diagnosis changed by the time of initial treatment, and whether change of FLIPI risk group impacted treated outcome. Patients and Methods: All adult (≥18 yo) patients with de novo follicular lymphoma (FL) treated at our center between 1998 and 2007 were evaluated. Study excluded patients with ≤2 follow up visits, known divergent of composite histology at diagnosis, and active concurrent malignancies. FLIPI was scored at diagnosis and at initiation of first treatment. For patients with missing FLIPI data, FLIPI category was scored if the omission did not alter the FLIPI category. Stable FLIPI risk group was defined as FLIPI score being low or intermediate at diagnosis and at initiation of first treatment (Low-Low, Int-Int). Progressed FLIPI risk group was defined by the population which changed categories from low or intermediate at diagnosis to a higher category at initiation of treatment (Low-Int, Low-High, Int-High). FLIPI scores were available for 570 patients at both diagnosis and initial treatment. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier method and compared by log-rank tests. Time of diagnosis was used as time origin for OS analyses. When OS analyses involved FLIPI score at the first treatment, time of the first treatment was used as the entry time to adjust the risk sets to account for the fact that FLIPI at first treatment is unknown before the onset of the first treatment. Chi-squared tests and Fisher's exact tests were used to compare categorical variables by FLIPI score change status. Progression free survival before and after 24 months (PFS24) of initial therapy were calculated. Results: For 898 FL patients, median follow up was 9.2 years (range 0.23 - 16.84), median OS not reached. Based on FLIPI at diagnosis, the 5 year OS is 97.2% for low risk, 93.0% for int risk, and 80.2% for high risk, 10 yr OS is 90.9% for low risk, 77.7% for int risk, and 67.6% for high risk. Of 570 patients with FLIPI at diagnosis and first treatment, median time to first treatment was 0.18 years (range 0-12.5) for patients with stable FLIPI (N=280) and 2.70 years (range 0.01-13.33) for patients with progressed FLIPI (N=83). For patients observed ≥ 6 and 12 months, the median time to first treatment was 1.21 years (N=47, range 0.51-12.5) and 2.49 years (N=29, range 1.0-12.5) for patients with stable FLIPI and 3.77 years (N=62, range 0.54-13.3) and 3.92 years (N=57, range 1.13-13.3) for patients with progressed FLIPI, respectively. Progressed FLIPI was observed in 14.6% (83/570) of patients. The incidence of progressed FLIPI was 51.4% (57/111) in patients observed ≥1 year before initiating therapy. Parameters contributing to progressed FLIPI compared to stable FLIPI were decreased hemoglobin (29% versus 6%), increased nodal areas affected (43% versus 2%) and higher LDH (37% versus 5%). Patients with stable FLIPI had longer PFS at 12 and 24 months, 88.6% versus 73.8% (P=0.006) and 79.3% versus 66.1% (P= 0.031) (Figure 1). Analysis of patients initially observed ≥ 6 or 12 months demonstrated that progressed FLIPI negatively affected OS and PFS (Figure 2, observed ≥ 12 month data not shown). Median PFS for patients observed ≥ 6 months was 8.36 years for stable FLIPI, 3.14 years for progressed FLIPI. At observation of ≥ 12 months, median PFS was 6.25 and 3.22 years for stable and progressed FLIPI, respectively. Increased FLIPI was associated with increased risk of transformation throughout the disease course (25% vs 16%, P=0.039). Conclusion: Progressed FLIPI between diagnosis and first line treatment is associated with a reduced PFS, and increased incidence of histologic transformation. In patients who are initially observed, a progressed FLIPI reduces OS and PFS. The effect on PFS may be related to treatment bias and ongoing analysis is underway. Progressed FLIPI potentially identifies a population with heightened risk of transformation. Disclosures Hamlin: Seattle Genetics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Novartis: Research Funding; Molecular Templates: Research Funding; Xencor: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Horwitz:Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy; Huya: Consultancy; Infinity: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Kumar:Celgene: Honoraria, Other: Scientific Advisory Board; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Adaptive Biotechnologies: Research Funding; Celgene: Research Funding. Moskowitz:Bristol Myers Squibb: Honoraria; Merck: Honoraria; Seattle Genetics: Honoraria, Research Funding. Moskowitz:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palomba:Pharmacyclics: Consultancy. Zelenetz:Gilead Sciences: Research Funding.

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The PRIMA-Prognostic Index (PI) Is Valid in Follicular Lymphoma (FL) Patients with Rituximab Chemo-Free First-Line Treatment

Blood ◽

10.1182/blood-2018-99-114866 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4150-4150 ◽

Cited By ~ 1

Author(s):

Eva Kimby ◽

Sandra Lockmer ◽

Harald Holte ◽

Björn E Wahlin ◽

Hans Hagberg ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Follicular Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Risk Group ◽

Bone Marrow Involvement ◽

First Line ◽

Advisory Committees

Abstract Background: Follicular lymphoma (FL) is a heterogenous disease. The optimal timing, sequence and choice of therapy remain matters of debate and there is no optimal prognostic tool. The FLIPI (Follicular Lymphoma International Prognostic Index) is based on five bio-clinical parameters and is widely used, but not as guide for choice of treatment. Recently a new prognostic score (PRIMA-PI), based solely on two parameters, bone marrow involvement and serum beta2 microglobulin (ß2m) was proposed for patients treated with immunochemotherapy (Bachy E., Blood 2018). The Nordic Lymphoma Group (NLG) performed two randomized trials including patients with symptomatic/progressive indolent CD20+ lymphoma, with rituximab monotherapy or rituximab in combination with interferon (IFN)-α2a as primary treatment, without maintenance (Kimby E., 2008, 2015). The 10 years follow-up of these patients showed a good survival with no major safety issues and no need for later chemotherapy in 38% of FL patients (Lockmer S, JCO 2018). Aim/Purpose: To evaluate two different prognostic systems (the new PRIMA-PI and the FLIPI), for overall survival (OS) and time to treatment failure (TTF) in a cohort of symptomatic/progressive FL patients treated with a rituximab-containing first-line regimen without chemotherapy. Methods: Previously untreated patients with a confirmed FL diagnosis (n=269) or indolent lymphoma not otherwise specified (n=22, most FLs with insufficient material for grading), treated in the NLG randomized trials with two cycles rituximab (375 mg/m2 x 4 weeks), with or without IFN-α2a, were classified into the three PRIMA-PI categories: high-risk: ß2m> 3mg / L, intermediate-risk: ß2m ≤ 3 mg / L with bone marrow involvement and low-risk: ß2m ≤ 3 mg / without bone marrow involvement. The FLIPI scores were also assessed. TTF, defined as the interval between randomization and either initiation of new lymphoma therapy due to relapse or intolerance, or death from any cause, as well as OS were estimated using the Kaplan Meier method. The log-rank test was used for comparison between risk groups. Results: Out of 291 patients, 252 had complete data on PRIMA-PI and FLIPI (at the time of randomization in the original trials) and were available for analyses of TTF and OS. Patient characteristics are shown in Table 1. PRIMA-PI seemed to identify a true high-risk group of 47 patients, 32 of them being high risk also according to FLIPI, while a larger patient group (n=117) was classified as FLIPI high-risk. After a long follow-up time, median 9.9 years (0.4 -18.8) from randomization, median 10.6 years for the 214 patients (74%) still alive, 76 patients (26%) were failure-free and 108 (37%) without need of any chemotherapy, Patients with PRIMA-PI high showed a shorter TTF compared to PRIMA-PI intermediate and low (Fig 1a), whereas the FLIPI risk-groups were not significantly separated (Fig 1b). Evidence of transformation to aggressive disease was seen in 55 patients, with no significant difference in frequency between the PRIMA-PI groups, nor between FLIPI groups. Both PRIMA-PI and FLIPI were of significant value for predicting OS, most evident after a long follow-up time (Fig 1c and d). In 41 patients the cause of death was progressive disease or therapy complications, regarded as lymphoma-related death, whereas 21 died of other causes. The lymphoma-specific survival was related to the PRIMA-PI (log-rank p=0.03), but not to the FLIPI (n.s). Prognosis was worse for the PRIMA-PI high-risk group than the for the low-risk, also when adjusted for sex, high age (>60 years), diagnosis, stage, ECOG and FLIPI risk-group; TTF HR 1.82 (95% CI 1.16-2.85, p=0.01) and OS HR 2.3 (95% CI 1.00-5.38, p=0.05). Conclusion: FL patients included in two NLG trials with complete clinical data and a median follow-up of >10 years after randomization have been assessed for validation of different prognostic indices. In these patients, all with chemo-free first-line therapy, the PRIMA-PI was shown a valid predictor of both TTF and OS and seemed more useful than the FLIPI. The PRIMA-PI high risk identified a group of patients (19% of all) with true poor prognosis. Disclosures Kimby: Roche: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Roche, Norway: Research Funding. Wahlin:Roche: Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Hagberg:Roche: Honoraria.

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Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽

10.1182/blood-2019-124192 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5263-5263

Author(s):

Karin Hohloch ◽

Christine Windemuth-Kieselbach ◽

Pier Luigi Zinzani ◽

Roberto E. Cacchione ◽

Wojciech Jurczak ◽

...

Keyword(s):

Follicular Lymphoma ◽

Mantle Cell Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Cell Lymphoma ◽

Primary Therapy ◽

First Line ◽

Advisory Committees ◽

Mantle Cell

To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

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Efficacy Outcomes of Treatments for Double Relapsed/Refractory Follicular Lymphoma (R/R FL): A Systematic Literature Review

Blood ◽

10.1182/blood-2020-136228 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 42-43

Author(s):

Brad S. Kahl ◽

Anik R. Patel ◽

Omer Zaidi ◽

Sonya J. Snedecor ◽

Anna G. Purdum

Keyword(s):

Clinical Trials ◽

Follicular Lymphoma ◽

Board Of Directors ◽

Clinical Data ◽

Research Funding ◽

Treatment Options ◽

Unmet Need ◽

Progression Free Survival ◽

Disease Stage ◽

Advisory Committees

ABSTRACT Introduction: Patients with indolent non-Hodgkin lymphomas (iNHL), including follicular lymphoma (FL), have high response to first-line treatment. However, retreatment is often required when relapses occur, and those with multiple relapses represent a patient population with an unmet need for effective treatment. Clinical data for several treatment options exist for the general relapsed and refractory (R/R) population; however, there are relatively fewer data specific to FL patients with ≥2 lines of prior treatment. This work systematically identified the available efficacy data in the double R/R FL population. Methods: The MEDLINE and EMBASE databases were searched through February 10, 2020. Studies were limited to interventional clinical trials of R/R FL patients (or mixed histologies with a predominance of FL) and articles published in English. Studies also must have reported one or more efficacy measures, such as overall response rate (ORR), complete response (CR), duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Potential interventions of interest were lenalidomide ± rituximab (R), duvelisib, ibrutinib, venetoclax, polatuzumab vedotin + R, obinutuzumab, copanlisib, umbralisib, idelalisib, and tazemetostat. Results: Of 35 publications examining treatment outcomes in R/R FL patients, only 14 (representing 5 unique clinical trials) were specific to the ≥ 2-line population. These trials were: CHRONOS Part B (copanlisib), DAWN (ibrutinib), DELTA (idelalisib), DYNAMO (duvelisib), and Morschhauser et al. 2019 (tazemetostat) and included a total of 605 participants. All studies used similar inclusion criteria, and patients included were similar in age (median 62-65), disease stage (III/IV), and ECOG score (0-2). Patients in the CHRONOS study had a median number of prior treatments of 2, whereas those in the DELTA study had 5. ORR ranged from 21% (ibrutinib) to 59% (copanlisib) (Table). The DoR ranged from 8.3 months in tazemetostat patients with EZH2 gene mutation to 19.4 months for ibrutinib. PFS ranged from 5.7 months in tazemetostat patients with wild-type EZH2 to 11.2 months for copanlisib. Median TTNT was only reported in the DAWN study (16 months). Conclusions: Very few clinical data exist reporting efficacy outcomes specific to the double R/R FL population. The limited data indicate that current treatments do not produce durable responses for most double R/R FL patients, demonstrating an unmet need. Further research is needed to fully understand the efficacy and safety of other potential interventions for this population. Disclosures Kahl: Genentech:Consultancy;Pharmacyclics LLC:Consultancy;AstraZeneca Pharmaceuticals LP:Consultancy, Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene Corporation:Consultancy;AbbVie:Consultancy;Roche Laboratories Inc:Consultancy;BeiGene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Acerta:Consultancy, Research Funding.Patel:Kite, a Gilead Company:Current Employment.Zaidi:BMS:Consultancy.Snedecor:Pharmerit - an OPEN Health Company:Other: Employment at consultancy paid by Kite Pharma to conduct this work.Purdum:Kite, a Gilead Company:Current Employment.

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Rituximab Plus Three Cycles of Dexamethasone In the Treatment of Immune Thrombocytopenia (ITP): a Pilot Study.

Blood ◽

10.1182/blood.v116.21.3697.3697 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3697-3697

Author(s):

Rebecca Elstrom ◽

Soo Y. Lee ◽

James B. Bussel

Keyword(s):

Platelet Count ◽

Pilot Study ◽

Board Of Directors ◽

Initial Treatment ◽

Research Funding ◽

Advisory Committees ◽

Equity Ownership ◽

Almost All

Abstract Abstract 3697 Introduction: Rituximab has been a useful treatment for patients with ITP; many hundreds of patients have been treated. 30–40% of patients will achieve a complete remission (CR: platelet count >150 × 109/l) with initial treatment and, of this group, the CR will last at least a year in almost all patients. However, emerging data suggests that at least 40% of these patients in CR will relapse between 1 and 3 years from initial treatment suggesting that long-term “cures” only occur in 20% of the initial patients. Therefore it would be desirable if CR's could be achieved in more patients and especially if these would be durable in more than 20%. One approach would be to use rituximab maintenance, however it results in suppression of B-cells for more than 2 years. Dexamethasone has also been used to achieve “cure” in ITP especially in adults at or near diagnosis. Cheng's study suggested that approximately 50% of patients would achieve a long-term response with only one 4-day cycle of high dose (40 mg/day) dexamethasone (N Engl J Med, 2003). A follow up study from GIMEMA suggested that 3–4 cycles of dexamethasone would be better than 1 cycle (Blood, 2007). Finally, Zaja's study suggested that rituximab plus one cycle of dexamethasone was superior to dexamethasone alone with a > 50% CR rate at 6 months (Blood, 2010). Therefore, we elected to perform a pilot study to explore the combination of rituximab with three cycles of dexamethasone at 14 day intervals. Methods: Patients with ITP with platelet counts < 30,000 off therapy and in need of treatment were enrolled. The standard dose (4 infusions of 375mg/m2) rituximab was given on days 1, 8, 15 and 22 and dexamethasone 40 mg (adjusted for size) on days 1–4, 15–18, and 29–32. Results: Fourteen patients between the ages of 4 and 53 years with ITP were treated with rituximab and dexamethasone (R&D) (Table 1). All had received previous steroid therapy as well as other treatments. The median platelet count was 40,000 at initiation of rituximab (range 7,000-230,000); several patients with low counts started with dexamethasone prior to initiating Rituximab to sustain their counts during initial treatment. Patients received rituximab weekly for between 2 and 4 doses and dexamethasone for either 2 or 3 courses at intervals between 1 and 8 weeks (median 2 week intervals). A summary of the results is shown in table 2 demonstrating short-lived platelet increases in response to dexamethasone in almost all patients. With short follow up, there were 7 CR's, 3 PR's and 4 NR's. If this was divided by duration of ITP prior to R&D, there were 4 CR's and 1 NR for ≤ 12 months and 3 CR, 3 PR, and 3 NR for > 12 months. More of the children who were treated had chronic disease than did adults explaining their apparently poorer response. Observed toxicities included hyperglycemia, grade 1 and 2 liver function abnormalities, weight gain, and 1 episode of colitis requiring hospitalization. Three patients opted to skip the third cycle of dexamethasone. Conclusion: A regimen of rituximab + 2–3 courses of dexamethasone is active in patients with pretreated ITP with appreciable but usually manageable toxicity. It appears to yield superior results if administered to patients within one year of diagnosis. This combination merits further exploration in a prospective clinical trial. Disclosures: Bussel: Portola: Consultancy; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc.: Membership on an entity's Board of Directors or advisory committees; Cangene: Research Funding; Genzyme: Research Funding.

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Consistent Benefit of Ruxolitinib Over Placebo in Spleen Volume Reduction and Symptom Improvement Across Subgroups and Overall Survival Advantage: Results From COMFORT-I

Blood ◽

10.1182/blood.v118.21.278.278 ◽

2011 ◽

Vol 118 (21) ◽

pp. 278-278 ◽

Cited By ~ 8

Author(s):

Srdan Verstovsek ◽

Ruben A. Mesa ◽

Jason Gotlib ◽

Richard S. Levy ◽

Vikas Gupta ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Symptom Severity ◽

Research Funding ◽

Risk Group ◽

Spleen Volume ◽

Advisory Committees ◽

Disease Subtype ◽

Baseline Hemoglobin

Abstract Abstract 278 Background: Overactive JAK-STAT signaling as a result of gain-of-function mutations (eg, JAK2V617F) and/or high circulating levels of inflammatory cytokines is considered to play a key role in the pathogenesis of myeloproliferative neoplasms. Ruxolitinib, a selective oral inhibitor of JAK1 and JAK2, demonstrated a significant reduction in spleen volume (SV) and improvements in myelofibrosis (MF)-related symptoms in a double-blind placebo-controlled trial (COMFORT-I). The objective of this analysis was to evaluate the efficacy of ruxolitinib across patient (pt) subgroups in COMFORT-I. Methods: Pts with MF were randomized to start placebo or ruxolitinib at a dose of 15 mg or 20 mg PO BID depending on baseline platelet count (100–200 ×109/L or >200 ×109/L, respectively). The dose was optimized for efficacy and safety during treatment. SV change was measured by MRI; MF symptoms were assessed using a daily diary (modified Myelofibrosis Symptom Assessment Form [MFSAF] v2.0) over 1 wk prior to dosing and throughout the 24 wks of dosing. The percent changes from baseline to wk 24 in SV and MFSAF Total Symptom Score (TSS, a measure of combined scores for abdominal discomfort, pain under ribs on left side, early satiety, itching, night sweats, and bone/muscle pain) were compared for ruxolitinib and placebo pts across the following subgroups: MF disease subtype, age, International Prognosis Scoring System (IPSS) risk group, presence/absence of JAK2V617F mutation, baseline hemoglobin, baseline spleen size (palpable spleen length), and baseline TSS. Survival was estimated by Kaplan-Meier method. Changes in SV and TSS Across Subgroups: 309 pts were randomized: 155 to ruxolitinib and 154 to placebo. Ruxolitinib demonstrated consistent benefit compared with placebo in both SV and TSS across all subgroups evaluated (Table). The impact of symptom severity on response was evaluated by baseline TSS quartiles (maximum score for TSS = 60). Ruxolitinib pts with baseline TSS of <8.5, 8.5-<16.5, 16.5-<25.5 and ≥25.5 had mean percent changes in SV of −28.0, −31.4, −31.7 and −34.8, respectively, vs +8.1 for all placebo pts combined. The mean percent change in TSS for these same subgroups was −40.5, −47.2, −48.1 and −48.2 vs +41.8 for all placebo pts combined. These data indicate that pts with modest to marked symptoms all benefit from ruxolitinib therapy in terms of both SV and TSS. Survival Analysis: 13 ruxolitinib and 24 placebo pts died during the study or during extended follow-up (median follow-up of 52 and 51 wks, respectively), representing a hazard ratio (95% CI) of 0.499 (0.254, 0.98) (p=0.0395). For ruxolitinib- and placebo-treated pts, respectively, the probability of survival (95% CI) >48 wks was 0.98 (0.92, 0.99) and 0.90 (0.81, 0.95) for pts with baseline hemoglobin values ≥10 g/dL and 0.84 (0.72, 0.91) and 0.77 (0.63, 0.86) for pts with baseline hemoglobin <10 g/dL. Conclusions: Pts receiving ruxolitinib had higher response rates than placebo based on reductions in SV and improvements in TSS at wk 24 regardless of baseline subgroup: MF disease subtype, age (≤65 or >65 y), IPSS risk group (intermediate-2 or high-risk), presence or absence of JAK2V617F mutation, hemoglobin level (≥10 g/dL or <10 g/dL), palpable spleen length (≤10 cm or >10 cm), and symptom severity (TSS quartile). In addition, the overall survival analysis suggested a benefit with ruxolitinib therapy over placebo. Disclosures: Verstovsek: Incyte: Research Funding. Mesa:Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding. Gotlib:Incyte: Consultancy, Research Funding. Levy:Incyte: Employment, Equity Ownership. Gupta:Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Catalano:Incyte: Honoraria; Novartis: Honoraria. Deininger:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Genzyme: Research Funding. Miller:Incyte: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau. Winton:Incyte: Consultancy. Arcasoy:Incyte: Research Funding. Lyons:Alexion: Consultancy, Honoraria; Telik: Research Funding; Incyte: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Research Funding. Vaddi:Incyte: Employment. Erickson-Viitanen:Incyte: Employment. Sun:Incyte: Employment. Sandor:Incyte: Employment. Kantarjian:Incyte: Research Funding; Novartis: Consultancy, Research Funding.

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Intervention Versus Observation: What Is the Appropriate Endpoint? Assessment of Endpoints in Patients with Advanced Stage Follicular Lymphoma Who Are Initially Observed

Blood ◽

10.1182/blood.v128.22.1777.1777 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1777-1777 ◽

Cited By ~ 1

Author(s):

Jacob D Soumerai ◽

Kurt S Bantilan ◽

Ai Ni ◽

Connie Batlevi ◽

Anna Alperovich ◽

...

Keyword(s):

Follicular Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Tumor Burden ◽

Advanced Stage ◽

Advisory Committees ◽

Kendall’S Tau ◽

Kendall's Tau ◽

Genetics Research ◽

Asymptomatic Patients

Abstract BACKGROUND: Treatment may be safely deferred in asymptomatic patients with advanced stage, low tumor burden follicular lymphoma (FL) until onset of symptoms or organ failure without compromising overall survival (OS). A randomized trial comparing immediate rituximab vs. observation in this setting reported a Time to New Treatment benefit without a corresponding OS benefit (Ardeshna et al, Lancet Oncol 2014). This is a comparison of Time to 1st Treatment (TT1T, observation arm) vs. Time to 2nd Treatment (TT2T, rituximab arm) and thus biased to immediate intervention. TT2T might be a less biased primary endpoint for trials evaluating immediate intervention vs. observation. Time to Treatment n (TT(n)T) is a function of cumulative time spent from diagnosis in periods of observation, treatment, and remission, and TT(n)T approaches OS as n approaches the maximum number of therapies received, thus we also hypothesize that TT2T might be a surrogate for OS. We have therefore performed a comprehensive evaluation of standard endpoints (TT1T, OS, and EFS12), described TT2T as a novel endpoint for trials evaluating intervention vs. observation in asymptomatic patients with advanced stage, low tumor burden FL, and aimed to determine if TT2T is a reliable surrogate for OS. METHODS: We identified 246 consecutive patients at our institution, diagnosed from 1998 to 2007 with advanced stage, low tumor burden follicular lymphoma grade 1-3A, for whom physician intention at diagnosis was observation. Median time to event was calculated using the Kaplan-Meier method for each event: TT1T, TT2T, and OS. Modified Kendall's tau was used to assess the correlation between TT1T, TT2T, and OS, accounting for censoring in these quantities. Tests of modified Kendall's tau against 0 (i.e. no correlation) were performed. EFS12 was defined as non-death event within 12 months of initiation of first treatment, and median OS for EFS12 analysis was calculated from end of first treatment. Of 69 patients who received chemoimmunotherapy as first therapy following initial observation, the log-rank test was used to compare survival distributions by EFS12. RESULTS: Of 246 patients with advanced stage, follicular lymphoma grade 1-3A for whom physician intention at diagnosis was observation, there was a slight female predominance (1.16:1), 34.6% were above age 60 with a median age of 56.1 years (range 25-88), and 11.8% (29/246) developed histologic transformation prior to 1st/2nd therapy, including 7.7% (19/246) prior to 1st treatment. At a median follow-up of 10.9 years: median TT1T was 43.5 months (3.5-217.4+, 179 events), median TT2T was 151.8 months (range 5.2-219.6+, 101 events), and median OS was not reached (range 5.2-219.6+, 48 events). The modified Kendall's tau measuring correlation between TT1T and OS was 0.012 (p = 0.537), and was 0.078 (p < 0.001) between TT2T and OS, suggesting that TT2T is strongly correlated with OS while TT1T is not. Failure to achieve EFS12 was observed in 10.3% (7/68) and associated with inferior OS (p=0.001). Of 7 patients who failed to achieve EFS12, 3 had histologic transformation. CONCLUSIONS: TT2T is a preferred primary endpoint for clinical trials evaluating intervention vs. observation. In patients with advanced stage, low tumor burden FL who are initially observed, the median time from diagnosis to 2nd treatment is 12.7 years. Future trials evaluating the role of immediate therapy in low tumor burden FL might restrict eligibility to high risk patients expected to have inferior TT2T. Efforts are ongoing to develop biomarkers (e.g. m7-FLIPI) that identify a population enriched with high risk patients. Our data also suggest that TT2T might be a better surrogate for OS than TT1T, and analyses are ongoing to validate this finding. Figure 1 Figure 1. Disclosures Hamlin: Molecular Templates: Research Funding; Seattle Genetics: Research Funding; Portola: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Xencor: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Horwitz:Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Huya: Consultancy; Infinity: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy; ADCT Therapeutics: Research Funding. Palomba:Pharmacyclics: Consultancy. Moskowitz:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Noy:Pharmacyclics, LLC, an AbbVie Company: Other: travel, accommodations, expenses, Research Funding. Kumar:Celgene: Research Funding; Pharmacyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Seattle Genetics: Research Funding; Celgene: Honoraria, Other: Scientific Advisory Board. Zelenetz:Amgen: Consultancy; Takeda Pharma: Consultancy; Novartis: Consultancy; Nanostring Tech: Consultancy; Portola Pharmaceuticals: Consultancy; Adaptive Biotechnology: Consultancy; Bristol Myers: Research Funding; Boehringer Ingelheim: Other: DMC Membership; Janssen: Consultancy, Research Funding; Hospira: Consultancy; Celgene: Consultancy; Gilead: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding.

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Updated Outcomes of Fludarabine/Melphalan/Bortezomib (Flu/Mel/Vel) Conditioning for Upfront Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.5885.5885 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5885-5885

Author(s):

Taiga Nishihori ◽

Claudio Anasetti ◽

Rachid Baz ◽

Jose L Ochoa-Bayona ◽

Kenneth H. Shain ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Hematopoietic Cell Transplantation ◽

Advisory Committees ◽

Allogeneic Hct ◽

Genetics Research ◽

Gvhd Prophylaxis ◽

Unrelated Donors

Abstract Background: Multiple myeloma remains incurable despite impressive array of available novel agents and therapeutic strategies. Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative option for patients with multiple myeloma but it is limited by its toxicities. We previously reported initial result of a phase 2 study of upfront allogeneic HCT in myeloma patients achieving at least very good partial response (VGPR) after initial therapy (Nishihori, et al. ASH 2013 abstract 3390) and here we report more mature results after a median follow up of 3 years. Methods: Twenty seven myeloma patients received allogeneic HCT between 01/2010 and 02/2015 at Moffitt Cancer Center (NCT 00948922). Eligible patients were age ≤ 60, achieving first ≥ VGPR or complete response (CR), and have 8/8 HLA-matched related or unrelated donors. Conditioning regimen consisted of fludarabine 30 mg/m2 for 4 days (days -6, -5, -4, and -3) and melphalan 70 mg/m2 for 2 days (days -4 and -3) followed by a single dose of bortezomib 1.3 mg/m2 on day -3 (Flu/Mel/Vel regimen). GVHD prophylaxis was initially left to the discretion of physicians but later modified to only tacrolimus/methotrexate. No maintenance therapy was prescribed after allogeneic HCT. Results: The median age at transplant was 50 (range, 25-58) years. Disease status at the time of allogeneic HCT was VGPR (n=17: 63%) and CR/stringent CR (n=10: 37%). All patients received unmanipulated peripheral blood stem cell grafts from HLA-matched related donors (n=14) or HLA-matched unrelated donors (n=13). Graft-versus-host disease (GVHD) prophylaxis was tacrolimus plus either methotrexate (n=19: 70%), or mycophenolate mofetil (n=4), or sirolimus (n=4). All patients achieved neutrophil engraftment with a median of 15 (range, 11-19) days. Platelet engraftment was achieved with a median of 17 (range, 13 - 35) days and 2 patients did not recover platelets. The cumulative incidences of grades II-IV and grades III-IV acute GVHD at day 100 were 63.6% (95% confidence interval (CI): 43.1-81.1) and 19.6% (95%CI: 5.4-39.9), respectively. The cumulative incidence of moderate to severe chronic GVHD was 56.4% (95%CI: 36.3-75.5) at 1-year. The cumulative incidences of transplant-related mortality at day 100, 1 year and 2 years were 7.4% (95%CI: 0.8-20.0), 11.1% (95%CI: 2.7-25.4), and 11.1% (95%CI: 2.7-25.4), respectively. Progression-free survival estimates at 1, 2, and 3 years were 74.1% (95%CI: 53.2-86.7), 65.1% (95%CI: 43.3-80.2), and 65.1% (95%CI: 49.9-87.5), respectively. With a median follow up of 39 months for surviving patients, overall survival estimates at 1, 2 and 3 years were 85% (95%CI: 64.9-94.1), 75.4% (95%CI: 52.6-88.3), and 69.1% (95%CI: 53.8-93.5), respectively. Conclusions: The results of the this phase 2 trial of upfront allogeneic HCT with fludarabine/melphalan/bortezomib (Flu/Mel/Vel) conditioning are promising and provide the rationale for reasonable potentially curative option to younger and fit patients who are eligible for upfront intensive consolidation strategy. This approach may be potentially valuable for those with high-risk myeloma and a multicenter study is currently being conducted (BMT CTN protocol 1302:NCT02440464). Disclosures Nishihori: Novartis: Research Funding; Signal Genetics: Research Funding. Baz:Takeda/Millennium: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Bristol-Myers Squibb: Research Funding; Signal Genetics: Research Funding. Shain:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen/Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Signal Genetics: Research Funding; Takeda/Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Alsina:Signal Genetics: Consultancy; Novartis: Research Funding; Takeda/Millennium: Research Funding; Amgen/Onyx: Consultancy, Speakers Bureau.

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Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group

Blood ◽

10.1182/blood-2021-149640 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3747-3747

Author(s):

Charlotte Doublet ◽

Marie-Sarah Dilhuydy ◽

Emmanuelle Ferrant ◽

Pierre Feugier ◽

Alexandra Fayault ◽

...

Keyword(s):

Retrospective Study ◽

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Oncology Nurses ◽

Advisory Committees ◽

Free Survival ◽

Daily Dose ◽

History Of

Abstract Median age at diagnosis of chronic lymphocytic leukemia is 72 years. However, only few patients over 80 years of age are included in clinical trials, even in those devoted to unfit patients. In order to evaluate both efficiency and safety of venetoclax in this category of patients, we conducted a multicentric retrospective study and collected data from 77 CLL patients from 19 FILO centers who started venetoclax after 80 years of age. Median age at venetoclax initiation was 86 years old (81-97). 63% of patients had a history of heart disease, 62% had renal failure (moderate 59% and severe 3%) and 29% had a history of severe infections. Despite their comorbidities and a CIRS greater than 6 in 70% of cases, their autonomy was preserved with a median performans status of 1 (0-4). In this comorbid geriatric population, pretherapeutic geriatric assessment was only performed in a single patient. The median number of prior therapies was 2 (0-6) with an exposure to a BCR inhibitor in 56% of cases. 11q and 17p deletion were found in 39% and 30% of cases respectively, 39% of patients had a complex karyotype and 30% harbored a TP53 mutation. However, in this real life population, these prognostic factors were only performed in half of patients. IGHV mutational status was only available in 11 patients, and 83% of them had unmutated IGHV. At the time of venetoclax initiation, the tumor lysis syndrome (TLS) risk was moderate in 57% of cases and high in 8% of cases. Venetoclax was administered as a single agent (42%) or in association with rituximab (58%). In total, half of the patients were hospitalized at each dose ramp-up, and only 3 patients were treated on outpatient basis. 82% of the cohort was able to reach the daily dose of 400mg. Half of the patients were included in a phone call monitoring program with oncology nurses to pre-emptively manage side effects and foster therapy adherence. The safety study reported 14% of TLS, with 2 discontinuations of treatment within the first month: one of which led to dialysis and the other to death. As in the previously published studies, 25% of patients had infectious complications, and grade 3 haematological and digestive toxicities were reported in 42% and 22% of cases, respectively. The reduction of the daily dose of venetoclax was necessary for 33%. Permanent discontinuation of venetoclax occurred in 40% of subjects, including 29% of early withdrawal (within the first 3 months). Main reasons for discontinuation were intolerance (21%), CLL progression (21%), death (21%) and scheduled treatment discontinuation (10%). The overall response rate was 86%, consisting of 49% of complete response (unconfirmed by bone marrow biopsy) and 37% of partial response. With a median follow-up of 21months, estimated progression free survival and overall survival were 29 and 38 months respectively. Prior exposure to a BCR inhibitor had no impact on progression free survival. To conclude, venetoclax has a manageable safety profile in elderly patients with comorbidities and can induce prolonged responses. Finally, if additional follow-up by oncology nurses seems to be more and more implemented, the pre-therapeutic onco-geriatric evaluation remains underexploited in this population. Disclosures Ferrant: AstraZeneca: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Other: Travel, Accommodations, Expenses. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. Laribi: AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; AbbVie: Other: Personal Fees, Research Funding; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding. Tchernonog: JANSSEN: Consultancy; ABBVIE: Consultancy; ASTRAZENECA: Consultancy. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Quinquenel: Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria.

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Cladribine Combined with Idarubicin and High-Dose AraC (CLIA2) As a Frontline and Salvage Treatment for Young Patients (≤65 yrs) with Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2018-99-119271 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4039-4039 ◽

Cited By ~ 1

Author(s):

Mansour Alfayez ◽

Hagop M. Kantarjian ◽

Farhad Ravandi ◽

Guillermo Garcia-Manero ◽

Marina Y. Konopleva ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Young Patients ◽

Multiparameter Flow Cytometry ◽

Intrathecal Therapy ◽

High Dose ◽

Advisory Committees ◽

Genetics Research ◽

Equity Ownership

Abstract Background Nucleoside analogues such as cladribine can increase the efficacy of cytarabine (araC) by modulating deoxycytidine kinase. The addition of cladribine to standard 7+3 chemotherapy has been shown to improve survival in pts with AML (Holowiecki JCO 2012). Results of our part-1 phase-2 clinical trial (cladribine combined with intermediate dose araC and idarubicin (CLIA1)) reported promising results that exceeded pretreatment expectations for response and tolerability (Jain, et. al. ASH 2016). Based on that, and the benefit of higher doses of cytarabine in younger patients (UK-MRC AML, Willemze JCO 2014), we investigated a higher dose of araC in combination with cladribine and idarubicin (CLIA2). Methods Non-APL, non-core binding factor AML pts 18-65 yrs of age with adequate organ function were enrolled in 1 of 3 cohorts: de novo AML, secondary AML (s-AML), or relapsed/refractory AML (R/R). Induction was cladribine 5 mg/m2 IV over 30 minutes on days 1-5, followed by araC 2g/m2 IV on days 1-5, and idarubicin 10 mg/m2 IV days 1-3. Consolidation consisted of up to 5 more cycles of CLIA2 for 3 days instead of 5. Dose-adjustments were allowed for age and PS. Sorafenib or midostaurin was added for pts with FLT3 mutations which occurred in 35% of pts on this study. Prophylactic intrathecal therapy was offered to higher risk pts at count nadir during cycle 1. Mutation profiling was performed using next generation sequencing prior to starting therapy. Results 65 patients were enrolled, with a median age of 47 yrs (range, 24-65): 37 pts (57%) in the frontline, 12 (19%) pts in the s-AML, and 16 (25%) in the R/R cohorts. Pt characteristics and outcomes by cohort are outlined in Table 1. The most commonly detected mutations at baseline were TET2 (45%), DNMT3a (37%), FLT3 (35%), ASXL1 (28%), and NPM1 (28%). Of 35 evaluable pts in the frontline cohort, 31 responded (ORR=89%) with 27 CR (77%) and 4 CRi (11%). Among the responders, 61% were negative for minimal residual disease (MRD [-]) by multiparameter flow cytometry. In the s-AML cohort, 10 pts were evaluable with an ORR of 60% (6/10) with 5 CR (50%) and 1 CRp (10%); 4 (67%) were MRD [-]. In the R/R cohort, 14 pts, previously treated with a median of 1 (1-4) prior therapy were evaluable for response. There were 7 CR (50%), 1 CRi (7%), for ORR of 57%; and 63% were MRD [-]. The median OS was not reached in the frontline and s-AML cohorts with median follow up of 5.2 and 11.5, months, respectively. In the R/R cohort, the median follow up was 4.7 months and median OS was 6.7 months [Figure.1]. Relapse-free survival was not reached in frontline and salvage cohort, and was 9.1 months in s-AML with median follow up of 5.2, 3.9, and 3.5 months in frontline, s-AML, and salvage cohorts, respectively [Figure.2]. The regimen was well tolerated. The most common ≥ grade 3 possibly-related non-hematologic adverse events were fever/infection (38), bleeding (2), and abnormal liver function test (3). Conclusion The 3-drug combination with a higher dose of araC, CLIA2, is safe and effective in younger pts with AML. Compared to our prior experience in pts with s-AML, using higher dose of cytarabine in CLIA2 for this cohort seems to have the highest impact. This trend however was also seen in the salvage and frontline cohorts when compared to the results from CLIA1. Response rates for pts in the newly-diagnosed AML, s-AML, and in the salvage settings are promising and should be explored further in larger studies and compared to current standard regimens. Disclosures Ravandi: Jazz: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Sunesis: Honoraria; Sunesis: Honoraria; Macrogenix: Honoraria, Research Funding; Orsenix: Honoraria; Jazz: Honoraria; Xencor: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Xencor: Research Funding; Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Bristol-Myers Squibb: Research Funding; Orsenix: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Research Funding; Abbvie: Research Funding. Konopleva:Stemline Therapeutics: Research Funding. Daver:Otsuka: Consultancy; Novartis: Consultancy; Incyte: Research Funding; Kiromic: Research Funding; Daiichi-Sankyo: Research Funding; Incyte: Consultancy; Novartis: Research Funding; ImmunoGen: Consultancy; Alexion: Consultancy; Sunesis: Consultancy; Pfizer: Research Funding; Pfizer: Consultancy; Karyopharm: Consultancy; Sunesis: Research Funding; BMS: Research Funding; ARIAD: Research Funding; Karyopharm: Research Funding. DiNardo:Bayer: Honoraria; Karyopharm: Honoraria; Abbvie: Honoraria; Celgene: Honoraria; Medimmune: Honoraria; Agios: Consultancy. Bose:Constellation Pharmaceuticals: Research Funding; Incyte Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Blueprint Medicines Corporation: Research Funding; Celgene Corporation: Honoraria, Research Funding; CTI BioPharma: Research Funding; Pfizer, Inc.: Research Funding. Andreeff:SentiBio: Equity Ownership; Jazz Pharma: Consultancy; Oncoceutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Eutropics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Astra Zeneca: Research Funding; Oncolyze: Equity Ownership; Celgene: Consultancy; Aptose: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Reata: Equity Ownership; Daiichi-Sankyo: Consultancy, Patents & Royalties: MDM2 inhibitor activity patent, Research Funding; United Therapeutics: Patents & Royalties: GD2 inhibition in breast cancer . Pemmaraju:abbvie: Research Funding; cellectis: Research Funding; samus: Research Funding; SagerStrong Foundation: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; Affymetrix: Research Funding; celgene: Consultancy, Honoraria. Jabbour:novartis: Research Funding. Cortes:novartis: Research Funding. Kadia:Abbvie: Consultancy; BMS: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Celgene: Research Funding; Takeda: Consultancy; Pfizer: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Abbvie: Consultancy; BMS: Research Funding; Jazz: Consultancy, Research Funding; Novartis: Consultancy; Amgen: Consultancy, Research Funding.

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Benchmark of Progression Free Survival for Multiple Lines of Therapy in Follicular Lymphoma Treated in the Rituximab Era

Blood ◽

10.1182/blood.v128.22.2955.2955 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2955-2955 ◽

Cited By ~ 3

Author(s):

Anna Alperovich ◽

Connie Batlevi ◽

Katy Smith ◽

Zhitao Ying ◽

Jacob D Soumerai ◽

...

Keyword(s):

Follicular Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Complete Response ◽

Line Treatment ◽

Advisory Committees ◽

Free Survival ◽

Third Line ◽

Third Line Treatment

Abstract Introduction In their lifetime, patients with follicular lymphoma frequently require multiple treatments, which have improved their survival over the past few decades. The expected treatment outcome based on lines of treatment in the post-Rituximab era is currently unknown. We analyzed the progression free survival and event free survival by line of treatment to aid estimating clinical endpoints when designing future clinical trials for multiply relapsed patients. Patients and Methods Adults (≥18 years) with de novo follicular lymphoma (FL) treated at our center between 1998 and 2007 were eligible (N=1134). 236 patients with ≤2 visits, mixed histology at initial diagnosis, and active concurrent malignancy were excluded. Of the remaining 898 patients, 105 were observed and did not require treatment during the timeframe of this dataset, and 2 had incomplete data, therefore 791 patients were eligible for response, progression and event free survival (PFS and EFS) analysis (Figure 1). Response was documented by investigators based on clinical or radiographic assessment. Complete response was based on radiographic assessment. PFS was defined as start of treatment to progression of disease or death. Patients with inadequate response to treatment, change of treatment, or stable disease without subsequent documented relapse were censored in the PFS analysis. Events for EFS were defined as progression, change of treatment, and death. PFS and EFS of sequential lines of treatment were evaluated by Kaplan-Meier method and compared across lines using log-rank test with adjustment for within-patient correlation. PFS and EFS were compared by other clinical variables using regular log-rank tests. Results Median age of diagnosis was 57.3 years with 1:1 male to female ratio. Median overall survival was not reached with median follow up of 9 years (N=898, range 0.2 - 16.8 years, Figure 1A). Median time to first treatment for the entire group was 2.3 months (range 0 - 13.3 years). In first line treatment of the 791 patients, 51% (N=406) received Rituximab with chemotherapy (R-Chemo), 13% (N=101) received chemotherapy only (Chemo), 19% (N=150) received Rituximab monotherapy (R-Mono), and 17% (N=129) received other treatments including radiation and surgery. For second line treatment, 405 patients were treated with about 37% receiving R-Chemo and 34% receiving R-Mono. As line of treatment increased, the percentage of patients with radiographically assessed complete response diminished from 71% at first line treatment to 25% by fifth line treatment (Figure 1B). Median PFS for first, second and third line treatment are 4.8, 1.6, and 1 year, respectively (Figure 2A). Median EFS for first, second and third line treatment are 3.8, 1.1, 0.8 year, respectively (Figure 2B). For subsequent lines of treatment, both median PFS and EFS were <1 year. Conclusion Follicular lymphoma is an indolent disease often requiring multiple lines of treatment. However, PFS and EFS for multiple lines of treatment in FL has not been described in the post-Rituximab era. The work has benchmarked the median response by line of treatment. After third line treatment, the PFS was ≤1 year. This analysis serves to aide comparison of different therapies for future drug approval in relapsed FL. Disclosures Hamlin: Xencor: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees. Horwitz:Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Huya: Consultancy; Infinity: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy; ADCT Therapeutics: Research Funding. Kumar:Celgene: Honoraria, Other: Scientific Advisory Board; Celgene: Research Funding; Adaptive Biotechnologies: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding. Moskowitz:Merck: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria. Moskowitz:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palomba:Pharmacyclics: Consultancy. Zelenetz:Gilead Sciences: Research Funding.

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