Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): High Efficacy of High Dose Chemotherapy and Autologous Stem Cell Transplantation (HDC auto-SCT). A Study of the Lymphoma Working Party (LWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Abstract Background: NLPHL is a relatively uncommon subtype of Hodgkin lymphoma (HL) accounting for about 5-6% of all HL cases. It has unique clinico-pathological, morphologic and immunohistochemical features with CD20-positive "lymphocyte predominant cells". Although long-term survival is better than in classical HL, frequent relapses are common and progression/transformation to aggressive non-Hodgkin lymphoma (NHL) may occur. Whilst HDC auto-SCT is considered as standard of care for relapsed/refractory classical HL, data on HDC auto-SCT in relapsed/refractory NLPHL is sparse. Here, we report a registry study of HDC auto-SCT for NLPHL using the EBMT database, representing the largest sample analyzed to date. Design: Eligible were patients with NLPHL18 years or older who underwent a first auto-SCT between 2003 and 2013, and were registered with the EBMT. Patients with NLPHL transformed to DLBCL were not eligible. The primary objective was 5-year progression-free survival (PFS). Baseline patient, disease and transplant data were collected from EBMT MED-A standard forms. Centers with potentially eligible patients were contacted to provide additional treatment and follow-up details with a copy of written diagnostic report for central review. Statistical analysis was descriptive and employed log rank comparisons for univariate assessment of the impact of baseline characteristics on survival endpoints. Results: We identified 92 patients who met the inclusion criteria with full data including a written diagnostic pathology report available. Of these, 36 patients were excluded after histopathology report review (17 classical HL, 2 NHL, 17 no sufficient information). The final sample comprised 56 patients. There was a predominance of male patients with a male:female ratio of 88%:12%. Median age was 36 (interquartile range (IQR) 29-50) years. Most patients (65%) had advanced stage (III-IV) at diagnosis and one third had B-symptoms. Prior to HDC auto-SCT, 71% patients had 2, 20% had 3, and the remainder had more than 3 lines of treatment (median: 2 lines). Rituximab was used in 62% of patients. The median time from diagnosis to HDC auto-SCT was 21 (IQR 14-51) months. Disease status prior to HDC auto-SCT was complete remission (CR) in 54% and partial remission (PR) in 43%. Most commonly used HDC was BEAM (84% patients), with additional rituximab in 13%. With a median follow-up of survivors of 5 (IQR 3.6-6.6) years, 5-year PFS and overall survival were 67% (95%CI 55-82) and 86% (95%CI 77%-96%), respectively. The 5-year incidence of relapse was 32% (95%CI 20-46). There were no transplant-related deaths. Univariate comparisons considering age, time from diagnosis to transplant, number of pre-treatment lines and rituximab use during induction, salvage and/or HDT failed to identify significant predictors of PFS or OS endpoints. Conclusions: This study, the largest reported thus far on HDC auto-SCT in NLPHL, shows that two thirds of patients remain free of disease 5 years after HDC auto-SCT. In contrast with the usual characteristics of patients with NLPHL, those included in this series had high-risk disease with B-symptoms and advanced stage at diagnosis, and half the patients had HDC auto-SCT less than 2 years after diagnosis. This study demonstrates that patients with NLPHL and adverse features can benefit from HDC auto SCT at relapse. Figure. Figure. Disclosures Montoto: Roche: Honoraria; Gilead: Research Funding. Masszi:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Moraleda:Pfizer: Research Funding. Bloor:Janssen: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees. Meissner:Amgen: Other: Travel Support; Takeda: Other: Travel Support; Celgene: Other: Travel Support; Teva: Other: Travel Support. Dreger:Novartis: Speakers Bureau; Gilead: Consultancy; Gilead: Speakers Bureau; Novartis: Consultancy; Janssen: Consultancy; Roche: Consultancy.

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ABVD Versus Escalated Beacopp in Advanced Stage Hodgkin's Lymphoma: Results from a Retrospective, Multicenter European Study

Blood ◽

10.1182/blood-2019-128198 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1565-1565 ◽

Cited By ~ 1

Author(s):

Patrizia Mondello ◽

Irene Dogliotti ◽

Jan-Paul Bohn ◽

Federica Cavallo ◽

Simone Ferrero ◽

...

Keyword(s):

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Advanced Stage ◽

Advisory Committees ◽

Free Survival ◽

High Risk Patients ◽

Risk Patients

Purpose: Hodgkin's lymphoma (HL) is a highly curable disease even in advanced-stage, with >90% of long-term survivors. Currently, the standard of care is ABVD (doxorubicin, etoposide, vinblastine and dacarbazine), as it is less toxic and as effective as other more intensive chemotherapy regimens. Alternatively, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) has been proposed as front-line intensified regimen with a better initial disease control and prolonged time to relapse when compared to ABVD. However, this advantage is associated with higher rates of severe hematologic toxicity, treatment-related deaths, secondary neoplasms and infertility. To date, the debate regarding which regimen should be preferred as first line for advanced-stage HL is still ongoing. To shed some light on this open question we compared efficacy and safety of both regimens in clinical practice. Patients and Methods: From October 2009 to October 2018, patients with HL stage III-IV treated with either ABVD or BEACOPP escalated (BEACOPPesc) were retrospectively assessed in 7 European cancer centers. Results: A total of 372 consecutive patients were included in the study. One-hundred and ten patients were treated with BEACOPPesc and 262 with ABVD. The baseline characteristics of the two groups did not differ significantly, except for a higher rate of high-risk patients in the BEACOPPesc group in contrast to the ABVD one (47% vs 18%; p= 0.003). Complete response rate (CR) assessed by PET imaging at the end of the second cycle was 67% and 78% for the ABVD and BEACOPPesc group (p= 0.003), respectively. Thirteen patients of the ABVD group achieved stable disease (SD) and 6 had a progression disease (PD). On the other hand, 4 of the patients in the BEACOPPesc group progressed, another 2 interrupted therapy because life-threatening toxicity. At the end of the therapy, CR was 76% in the ABVD group and 85% in the BEACOPPesc group (p= 0.01). A total of 20% patients in the ABVD group and 14% patients in the BEACOPPesc group received consolidation radiotherapy on the mediastinal mass at the dose of 30Gy. After radiotherapy, the number of patients with CR increased to 79% and 87% in the two groups (p= 0.041), respectively. Thirty-nine patients (35%) in the BEACOPPesc group required dose reduction of chemotherapy due to toxicity compared to 12 patients (5%; p= <0.001) in the ABVD group. Overall, the rate of severe toxicities was higher in the BEACOPPesc group in comparison with the ABVD cohort. In particular, there was a significant increased frequency of acute grade 3-4 hematologic adverse events (neutropenia 61% vs 24%; anemia 29% vs 4%; thrombocytopenia 29% vs 3%), febrile neutropenia (29% vs 3%), severe infections (18% vs 3%). Myeloid growth factors were administered to 85% and 59% of patients in the BEACOPPesc group compared to the ABVD group. Blood transfusions were required in 51% and 6% of patients in the BEACOPPesc group compared to the ABVD cohort. Progression during or shortly after treatment occurred in 5 patients in the BEACOPPesc group (4%) and in 16 patients in the ABVD group (6%; p= 0.62). Among the 96 patients who achieved a CR after BEACOPPesc and radiotherapy, 8 relapsed (8%), compared to 29 of 208 patients in the ABVD group (14%; p= 0.04). At a median follow-up period of 5 years, no statistical difference in progression free survival (PFS; p=0.11) and event-free survival (EFS; p=0.22) was observed between the BEACOPPesc and ABVD cohorts. Similarly, overall survival (OS) did not differ between the two groups (p=0.14). The baseline international prognostic score (IPS <3 vs ≥ 3) significantly influenced the EFS with an advantage for the high-risk group treated with BEACOPPesc (Figure 1A; p=0.03), but not the PFS (Figure 1B; p=0.06) and OS (Figure 1C; p=0.14). During the follow-up period, in the BEACOPPesc group one patient developed myelodysplasia and one acute leukemia. Second solid tumors developed in one patient in the ABVD group (lung cancer) and one in BEACOPPesc group (breast cancer). Conclusion: We confirm that the ABVD regimen is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control especially in high-risk patients, the long-term outcome remains similar between the two regimens. Disclosures Ferrero: EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau. Martinelli:BMS: Consultancy; Pfizer: Consultancy; ARIAD: Consultancy; Roche: Consultancy; Novartis: Consultancy. Willenbacher:European Commission: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Myelom- und Lymphomselbsthilfe Österreich: Consultancy, Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Science: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; IQVIA: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; oncotyrol: Employment, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fujimoto: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tirol Program: Research Funding; Abbvie: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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The Outcome of Treatment-Free Remission after First-Line Nilotinib or Dasatinib in Chronic Phase Chronic Myeloid Leukemia Patients Is Different

Blood ◽

10.1182/blood-2021-146722 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2552-2552

Author(s):

Franck E. Nicolini ◽

Vincent Alcazer ◽

Stephanie Dulucq ◽

Sandrine Hayette ◽

Jean-Michel Cayuela ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Chronic Phase ◽

Median Dose ◽

First Line ◽

Advisory Committees ◽

French Group ◽

Treatment Free Remission ◽

The Impact

Abstract Aims: The absolute number of chronic phase CML patients (pts) reaching the treatment-free remission (TFR) criteria has been substantially increased by the use of second-generation TKI (TKI2), initiated since diagnosis, comparing to Imatinib first-line. However, the relative rate of unsuccessful TFR (i. e. pts loosing their MMR after TKI2 cessation) still remains around 50% at 2 years and beyond, whatever the TKI2 was. The aim of this study is to analyse the rate of successful TFR in pts receiving Nilotinib (Nilo) or Dasatinib (Dasa) first-line obtaining the appropriate criteria. Methods: Observational retrospective study in 3 reference centers of the French group of CML lead between 2010 and 2021. Eligible pts were CP CML pts initiating either Nilo 300 mg BID or Dasa 100 mg daily since diagnosis, until cessation for sustained MR4.5 (i.e. ≥2 years on ≥4 datapoints). Data were retrospectively collected according to the national regulations with pts' information. All pts were assessed and followed according to ELN recommendations 2009, 2013 and 2020 along treatment and to the recommendations from the French group of CML (D. Rea et al., Cancer 2018) for TFR. In this regard, the TKI2 was resumed in case of loss of MMR. All BCR-ABL1 assessments were performed in the 3 reference laboratories, standardised and expressed in % (IS) with ≥32,000 copies of ABL1 as control. All patients were harbouring major BCR-ABL1 transcripts. The primary endpoint was the survival without loss of MMR after TKI2 cessation. The secondary endpoints were the kinetics of MMR loss, and the identification of factors influencing MMR loss. Results: Seventy-two pts were reported (47 Nilo, 25 Dasa) with 57% females with a median age at diagnosis of 48 (36.75-61.25) years. The median follow-up since diagnosis was 9.26 (3.75-13.75) years (8.8 for Nilo and 9.47 for Dasa p=ns) and after TKI2 cessation 3.94 (0.7-8.8) years (3.92 for Nilo and 3.90 for Dasa p=ns). Sokal scores were 42% Low, 41% Intermediate, 17% High in Nilo and 39% L, 25% I and 35% H in Dasa pts (p=ns). ELTS scores were 50% L, 22% I, 9.5% H (18.5% Uk) in Nilo and 46.5% L, 28.5% I and 3.5% H (21.5% Uk) in Dasa pts (p=0.95). Five (9%) pts harboured ACA at diagnosis in the Nilo group and 2 (7%) in the Dasa group (p=1.00). The median time from TKI2 initiation to sustained MR4.5 was 19 (3.12-36) months in the Nilo group and 16 (6.3-39) months in the Dasa group (p=0.644). The duration of sustained MR4.5 until cessation was 3.04 (1.5-9.3) years for Nilo and 2.65 (1.11-7.95) for Dasa (p=0.96). The median dosing of Nilo was 600 (300-800) mg daily and 80 (20-100) mg at TKI2 cessation. None of these patients switched to another TKI during the follow-up. TKI2 cessation occurred after 60.5 (43-74.5) months in the Nilo group and 68 (39-90) months in the Dasa group (p=0.581). Thirty-seven pts out of 47 (79%) were BCR-ABL1 undetectable at Nilo cessation 18/25 (72%) at Dasa cessation (p=0.60). At M3 after discontinuation, 58% of pts remained undetectable after Nilo cessation and 30.4% after Dasa cessation (p=0.05).The median survival of pts without loss of MMR was not reached in the Nilo group, and was 14 (4.73-NR) months in the Dasa group, (p=0.042) as analysed by the KM method (Figure 1.). Two patients died (1 Nilo, 1 Dasa) from competing events (solid tumours) after unsuccessful TFR. Twenty-eight pts (14 Dasa, 14 Nilo) restarted their TKI2 after MMR loss and all regained ≥ MMR after 3 months of Dasa at a median dose of 75 (40-100) mg daily and all except one (who regained MMR at M12) after resumption of Nilo at a median dose of 350 (300-600) mg daily. Univariate analysis identified pts with H+I Sokal (as compared to low) as an unfavourable factor for successful TKI2 cessation [HR=0.35 (0.15-0.83), p=0.017] and type of TKI2 (Nilo as reference vs Dasa) was discriminant [HR=2.1 (1.01-4.35), p=0.047]. Multivariate analysis identified the type of TKI2 as a significant factor impacting on TFR outcome [HR 2.11 (0.97-4.55], p=0.05]. Conclusions: As it is likely that no prospective head-to-head comparison will be performed in this setting, on this limited series of pts, we conclude that the outcome of TFR seems to be different according to the TKI2 used since diagnosis, suggesting the impact of distinct biological variables modified by the type of TKI2 on the long run (such as immunological system, BM micro-environment, others) on TFR outcome. Figure 1 Figure 1. Disclosures Nicolini: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses, Research Funding; Kartos Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sun Pharma Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Incyte Biosciences: Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Etienne: Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Rea: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Potential Impact of Consolidation Radiation Therapy for Advanced Hodgkin Lymphoma: A Secondary Modeling of SWOG S0816 with Receiver Operating Characteristic Analysis

Blood ◽

10.1182/blood-2018-99-113133 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2927-2927 ◽

Cited By ~ 1

Author(s):

Chul S. Ha ◽

Hongli Li ◽

Heiko Schoder ◽

Chelsea C Pinnix ◽

Elizabeth Brem ◽

...

Keyword(s):

Radiation Therapy ◽

Board Of Directors ◽

Hodgkin Lymphoma ◽

Research Funding ◽

Residual Disease ◽

Entire Group ◽

Advisory Committees ◽

Potential Impact ◽

Receiver Operating

Abstract Background:The role of radiation therapy (XRT) for advanced stage Hodgkin lymphoma (HL) is controversial. In the HD15 trial, the German Hodgkin Study Group (GHSG) administered XRT for PET-positive residual disease ≥2.5 cm at least 2 weeks after completion of chemotherapy and showed 91.5 % in-field control rate with a median follow-up of 102 months (Engert, A; personal communication). However, there is no comparison arm where patients with PET-positive residual disease ≥2.5 cm did not receive XRT. SWOG S0816 was a US intergroup trial utilizing ABVD-based therapy with response adaptation based on interim PET imaging; XRT was not allowed per protocol, and counted as an event. In this analysis, we identified patients in S0816 who would have met HD15 criteria for XRT, but did not receive XRT per design. We then modeled the potential impact of XRT on disease control. Patients and Methods:Of 336 eligible and evaluable HIV-negative patients enrolled in S0816, 49 had an end-of-treatment PET (termed "PET3," to be done 6-8 weeks after completion of chemotherapy) that was positive (i.e. Deauville 4-5) upon central review. We simulated the progression free survival (PFS) if XRT had been delivered per HD15 criteria (PET positive disease and ≥2.5 cm), evaluating by assumptions of 50, 80 and 90% control of the disease within the XRT fields. Receiver operating characteristics (ROC) analyses were performed with additional size cut-off points of 2.0 and 1.5 cm. Results:The median follow-up for the 49 PET3 positive patients was 71 months (range 9.7-92.6). For these 49 patients, the observed landmark PFS at 2 years after the date of PET3 was 30.6%. Twenty-four (49%), 33(67%), and 40 (82%) of the 49 patients had at least one site of disease that met the HD15 criteria for XRT with ≥2.5 cm, ≥2.0 cm, and ≥1.5 cm size cut-offs respectively. Sixteen, 19, and 25 patients had disease progression respectively from each group at median of 1.4-1.5 months. Twelve, 12, and 15 patients had relapses limited to the sites that would have been radiated following HD15 criteria with ≥2.5 cm, ≥2.0 cm, and ≥1.5 cm respectively. Estimated landmark PFS at 2 years for the 49 PET3 positive patients assuming 50, 80, and 90 % control of the disease within the radiated sites following HD15 guideline with ≥2.5 cm, ≥2.0 cm, and ≥1.5 cm cut-off are summarized in columns A, B, and C of the table respectively. For the entire group of 336 patients, the observed PFS at 2 years was 79%. Estimated 2-year PFS for the entire group of 336 patients assuming 50, 80, and 90 % control of the disease within the radiated sites following HD15 guideline with ≥2.5 cm, ≥2.0 cm, and ≥1.5 cm cut-off are in columns D, E, and F of the table respectively. Conclusion: Among the PET3 positive patients, consolidation XRT per HD15 criteria with cut-off points of 2.5, 2.0, and 1.5 cm could have raised the 2-year PFS by 12-28 % assuming 50-90% local control within radiated sites. However, the improvement in PFS is more moderate at 1.6-3.9 % if we consider the entire cohort of 336 patients. Although there may be some gain in PFS as the cut-off point is lowered by our ROC analysis, one needs to consider the trade-off against potentially increasing normal tissue toxicity as more sites are irradiated. Table. Table. Disclosures Brem: Pharamcyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees. Bartlett:Merck & Co: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ImaginAB: Research Funding; Janssen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Millennium: Research Funding; Genentech: Research Funding; Astra Zeneca: Research Funding; Pharmacyclics: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Meyers Squibb: Research Funding; Affimed: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding. Evens:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Affimed: Consultancy; Janssen: Consultancy; Tesaro: Research Funding; Bayer: Consultancy; Acerta: Consultancy; Pharmacyclics International DMC: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy. Rimsza:NanoString: Other: Inventor on the patent for the Lymph2Cx assay. Leonard:Novartis: Consultancy; Celgene: Consultancy; MEI Pharma: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; United Therapeutics: Consultancy; BMS: Consultancy; Biotest: Consultancy; Sutro: Consultancy; Karyopharm: Consultancy; Juno: Consultancy; Gilead: Consultancy; Genentech/Roche: Consultancy; Pfizer: Consultancy; Bayer: Consultancy. Kahl:Seattle Genetics: Consultancy; Genentech: Consultancy; Acerta: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; ADC Therapeutics: Consultancy; CTI: Consultancy; Gilead: Consultancy; Juno: Consultancy; Celgene: Consultancy. Smith:BMS: Consultancy; Portola: Honoraria. Friedberg:Bayer: Honoraria.

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Predictive Factors of Response and Survival of Lenalidomide and Rituximab As Initial Treatment of Follicular Lymphoma

Blood ◽

10.1182/blood-2019-129311 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1533-1533 ◽

Cited By ~ 1

Author(s):

Paolo Strati ◽

Ralph J. Johnson ◽

Sheryl G Forbes ◽

Loretta J. Nastoupil ◽

Felipe Samaniego ◽

...

Keyword(s):

Board Of Directors ◽

Initial Treatment ◽

Research Funding ◽

Advisory Board ◽

Advanced Stage ◽

Advisory Committees ◽

Long Term Follow Up ◽

Baseline Characteristics

Introduction. The combination of rituximab and lenalidomide (R2) is active in patients with untreated indolent lymphoma. Recent randomized trials (RELEVANCE) have demonstrated similar efficacy when compared to standard chemo-immunotherapy backbones. Long term follow up of patients receiving R2 as well as predictors of long term remission and survival have yet to be published. Methods. We prospectively evaluated patients with low grade advanced stage FL who received R2 as initial treatment at our institution between 07/2008 and 10/2014. Lenalidomide was given at 20 mg (day 1-21, in a 28 day cycle) for 6 cycles with rituximab monthly. Lenalidomide starting dose was 10 mg if baseline creatinine clearance was < 60 mL/min. Patients with an objective response continued with 10-20 mg of lenalidomide with rituximab for up to 12 more cycles. Response was evaluated according to 2014 Lugano criteria. Results. One-hundred and one patients were included in the analysis, baseline characteristics are shown in the Table. Median number of provided cycles was 7 (range, 1-20). Median dose of lenalidomide was 20 mg (range, 5-20 mg), and 29 (29%) patients required a dose reduction. Fifty-six (55%) patients experienced grade 3-4 treatment-related toxicities, the most common (> 5%) being neutropenia (39%), skin rash (20%), myalgia (16%) and fatigue (16%). Seven (7%) patients discontinued treatment before completion, after a median time of 4 months (range, 1-10 months): 4 because of toxicity (arterial thrombosis in 2, respiratory failure in 1, and skin rash in 1), and 3 because of progression. Ninety-eight patients were evaluable for response, while 3 patients discontinued treatment because of toxicity before first response assessment. Overall response rate was 98%, CR rate 90% (both achieved after a median of 6 months [range, 3-22 months]), and CR rate at 30 months (CR30) was 80%. Only female sex associated with a higher CR rate (96% vs 83%, p=0.05), while no baseline characteristic associated with CR30 rate. After a median follow-up of 88 months (95% confidence interval, 84-92 months), 31 (31%) patients progressed and/or died, 7-year progression-free survival (PFS) was 63%, and 13% of patients had a PFS < 24 months (PFS24). Failure to achieve CR was the only factor associated with significantly decreased PFS (10 months vs not reached, p<0.001) and higher likelihood of PFS24 (46% vs 5%, p<0.001). No association was observed with baseline characteristics, including FLIPI and FLIPI-2 score. At most recent follow-up, transformation was reported in 3 (3%) patients, after 30, 32 and 42 months, respectively. Two (2%) patients have died, 1 of unrelated comorbid health conditions, 1 of progressive disease, and 7-year overall survival was 98%. Second cancers (excluding transformation) were diagnosed in 8 (8%) patients, after a median of 55 months (range, 3-105 months). These included: breast adenocarcinoma (2), melanoma (2), pancreatic adenocarcinoma (1), esophageal adenocarcinoma (1), and therapy-related acute myeloid leukemia. Discussion. Long-term follow-up show very favorable outcomes for patients with advanced stage FL receiving R2 as initial treatment, independent of traditional prognostic factors relevant to patients treated with chemoimmunotherapy, including FLIPI and FLIPI-2 score. Combination strategies, aimed at increasing depth of response to R2, may further improve outcomes observed with this regimen. Table. Disclosures Nastoupil: Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Spectrum: Honoraria. Westin:Janssen: Other: Advisory Board, Research Funding; Unum: Research Funding; Curis: Other: Advisory Board, Research Funding; 47 Inc: Research Funding; Genentech: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Celgene: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Novartis: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding. Wang:AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding; BioInvent: Consultancy, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Research Funding; Dava Oncology: Honoraria; Celgene: Honoraria, Research Funding; Aviara: Research Funding; Kite Pharma: Consultancy, Research Funding; Guidepoint Global: Consultancy; VelosBio: Research Funding; Loxo Oncology: Research Funding. Neelapu:Pfizer: Consultancy; Precision Biosciences: Consultancy; Merck: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Allogene: Consultancy; Novartis: Consultancy; BMS: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Cellectis: Research Funding; Acerta: Research Funding; Karus: Research Funding; Poseida: Research Funding; Incyte: Consultancy; Cell Medica: Consultancy; Unum Therapeutics: Consultancy, Research Funding. Fowler:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: lenalidomide and rituximab are not yet FDA-approved as frontline treatment for patients with FL

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90Y-Ibritumomab Tiuxetan (Zevalin®) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

Blood ◽

10.1182/blood.v116.21.594.594 ◽

2010 ◽

Vol 116 (21) ◽

pp. 594-594 ◽

Cited By ~ 8

Author(s):

Anton Hagenbeek ◽

John Radford ◽

Achiel Van Hoof ◽

Umberto Vitolo ◽

Ama Z.S. Rohatiner ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Induction Therapy ◽

Research Funding ◽

Myelogenous Leukemia ◽

Control Group ◽

Advanced Stage ◽

Ibritumomab Tiuxetan ◽

Advisory Committees

Abstract Abstract 594 The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39–0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42–0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27–0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30–1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were – for the greater part – rituximab-naïve. Disclosures: Hagenbeek: Roche Global Advisory Board: Consultancy. Radford:Schering (May 2009): Honoraria, Membership on an entity's Board of Directors or advisory committees. Vitolo:Roche Italy: Membership on an entity's Board of Directors or advisory committees; Celgene Italy: Membership on an entity's Board of Directors or advisory committees. Soubeyran:Roche: Honoraria, Research Funding; Cephalon: Research Funding. Bischof Delaloye:Expert Statement (questions of reimbursement in Switzerland): Honoraria. Morschhauser:Roche: Honoraria, Paid expert testimony within the past 2 years; Bayer: Honoraria.

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Enestnd 4-Year (y) Update: Continued Superiority of Nilotinib Vs Imatinib in Patients (pts) with Newly Diagnosed Philadelphia Chromosome–Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

Blood ◽

10.1182/blood.v120.21.1676.1676 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1676-1676 ◽

Cited By ~ 13

Author(s):

Hagop M. Kantarjian ◽

Dong-Wook Kim ◽

Surapol Issaragrisil ◽

Richard E Clark ◽

Josy Reiffers ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Standard Of Care ◽

Molecular Response ◽

Newly Diagnosed ◽

Advisory Committees ◽

Molecular Responses ◽

The Difference ◽

The Impact

Abstract Abstract 1676 Background: Pts treated with nilotinib in the ENESTnd phase 3 trial achieved higher and faster rates of major molecular response (MMR, ≤ 0.1% BCR-ABLIS), deeper molecular responses (MR4, ≤ 0.01%IS and MR4.5, ≤ 0.0032%IS), significantly lower rates of progression to accelerated phase/blast crisis (AP/BC), and fewer CML-related deaths compared with imatinib by 1, 2, and 3 y. Here, we report data with a minimum follow-up of 3 y; efficacy and safety data based on longer follow-up of 4 y will be presented to further assess the impact of nilotinib vs imatinib in pts with newly diagnosed Ph+ CML-CP. Methods: Adult pts (N = 846) with newly-diagnosed Ph+ CML-CP were randomized to nilotinib 300 mg twice daily (BID; n = 282), nilotinib 400 mg BID (n = 281), or imatinib 400 mg once daily (QD; n = 283). MMR, MR4, MR4.5, time to progression to AP/BC, progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Significantly higher rates of MMR, MR4, and MR4.5 by 3 y were achieved in nilotinib- vs imatinib-treated pts (Table). Nilotinib led to the achievement of higher rates of molecular responses regardless of Sokal risk group or age. The difference in the rates of both MR4 and MR4.5 continued to be significantly higher for nilotinib, with the difference in favor of nilotinib increasing from 1 to 3 y (MR4: 9%-14% difference by 1 y, 18%-24% difference by 3 y; MR4.5: 6%-10% difference by 1 y, 13%-17% difference by 3 y). Among patients who achieved MMR, more pts achieved MR4 or MR4.5 on nilotinib 300 mg BID (68%) and nilotinib 400 mg BID (62%) compared with imatinib (49%). No pt in any arm progressed after achieving MR4.5. Significantly fewer pts progressed to AP/BC on nilotinib vs imatinib (Table). No new progressions occurred on core treatment between the 2-y and 3-y analyses. When events occurring after treatment discontinuation were included, the rates of progression to AP/BC were also significantly lower with nilotinib vs imatinib (Table). Nearly twice as many pts had emergent mutations on imatinib (n = 21) vs either nilotinib arm (n = 11 in each arm), with 5 pts overall developing mutations between 2 and 3 y. OS remained similar in all groups at 3 y, but fewer CML-related deaths occurred in both the nilotinib 300 mg BID (n = 5) and 400 mg BID (n = 4) arms vs imatinib (n = 14). Both drugs were well tolerated. Few new adverse events (AEs) and laboratory abnormalities were observed between 2 and 3 y. Rates of discontinuation due to AEs were 10%, 14%, and 11% in the nilotinib 300 mg BID, nilotinib 400 mg BID, and imatinib arms, respectively. Conclusions: Nilotinib continues to demonstrate superiority vs imatinib, yielding faster and deeper molecular responses and a significantly decreased risk of progression. Results of ENESTnd support the use of nilotinib as a standard of care option in newly diagnosed adult pts with Ph+ CML-CP and should be considered to replace imatinib as the standard-of-care frontline therapy for patients with Ph+ CML-CP. Disclosures: Kantarjian: Novartis: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding. Kim:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ARIAD: Research Funding; II-Yang: Research Funding. Clark:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Reiffers:BMS: Expense reimbursement for travel expenses Other; Novartis: Expense reimbursement for travel expenses, Expense reimbursement for travel expenses Other. Nicolini:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Ariad: Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria. Hughes:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria; CSL: Research Funding. Hochhaus:BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding. Kemp:Novartis Pharmaceuticals Corp: Employment. Fan:Novartis Pharmaceuticals Corp: Employment. Waltzman:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Saglio:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy. Larson:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy; Ariad: Consultancy, Research Funding.

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Long-Term AL Amyloidosis Survivors Among Non-Selected Referral Population

Blood ◽

10.1182/blood-2018-99-117802 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3226-3226

Author(s):

Eli Muchtar ◽

Morie A. Gertz ◽

Martha Q. Lacy ◽

David Dingli ◽

Francis K. Buadi ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Survival Rates ◽

Al Amyloidosis ◽

Advisory Committees ◽

Term Survival ◽

Long Term Survival ◽

Long Term Survivors

Abstract Introduction: Prognosis of AL amyloidosis has improved in recent years; however for many patients prognosis remains poor. We aimed to define patient-, disease- and treatment characteristics which are associated with long-term survival. Method: A retrospective chart review of all patients with biopsy-proven systemic AL amyloidosis, who were seen within 90 days of the confirmed diagnosis. Long-term survival was defined as 5-year and 10-year survival from the time of diagnosis. For 5-year survival we selected patients seen between January 1, 2000 and December 31, 2012 (allowing a minimum of 5-year follow-up, n=1331) and for 10-year survival we screened patients seen between January 1, 2000 and December 31, 2007 (allowing a minimum of 10-year follow-up; n=779). Treatment allocation was defined as the first regimen given, irrespective of subsequent treatment modifications. Results: Of the screening population, 498 patients survived ≥5 years from diagnosis (37% of the 5-year screening cohort) and 168 patients survived 10 years or more (22% of the 10-year screening cohort). Five-year survivors and 10-year survivors as compared to their counterparts were (Table): younger, higher proportion of women, more likely to have single organ involvement, less heart/liver/nerve involvement and more kidney involvement. Long-term survivors also had lower bone marrow plasma cell percentage at the time of diagnosis and lower tumor burden measured by the difference between involved to uninvolved light chain (dFLC). Similarly, long-term survivors had lower Mayo stages and higher systolic blood pressure. No difference in light chain isotype was observed between long-term survivors to long term non-survivors. Long-term survivors were less likely to be seen within 30 days of diagnosis compared to their counterparts (52% among 5-year survivors vs 67% among 5-year non-survivor; P<0.001). FISH abnormalities (data available for 555/1331 patients, 42%) were comparable between groups with regard to t(11;14) (50% among 5-year survival compared to 50% among 5-year non-survivors; P=0.93) and 13q abnormalities (34% vs 36%, respectively; P=0.53). However, trisomies were less frequently encountered in the 5-year survivor group (20% vs 29%, respectively; P=0.01), and far less common among 10-year survivors (11% vs 26%, respectively; P=0.04). Autologous stem cell transplantation (ASCT) was more likely to be associated with long-term survival. Of all patients who underwent ASCT, 74% survived more than 5 years and 49% survived more than 10 years. In comparison, among the standard-intensity therapies, 5-year survival rates for melphalan-dexamethasone, bortezomib-based regimens, immunomodulatory drug-based regimens and single agent dexamethasone/ melphalan-prednisone were 29%, 28%, 30% and 10%, respectively. The corresponding 10-year survival rates were 15%, 20%, 20% and 5%, respectively. Conclusions: Long-term AL survivors have distinct favorable baseline characteristics (including those introduced by referral bias) and ASCT as their initial therapy. Identification of these patients, especially the Mayo 2004 stage III and the Mayo 2012 stage III-IV patients who unexpectedly survived 10 years, will allow for further study and insights. Disclosures Gertz: Teva: Consultancy; Prothena: Honoraria; Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Physicians Education Resource: Consultancy; Research to Practice: Consultancy; Amgen: Consultancy; janssen: Consultancy; Apellis: Consultancy; Medscape: Consultancy; Abbvie: Consultancy; spectrum: Consultancy, Honoraria; annexon: Consultancy. Lacy:Celgene: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Russell:Vyriad: Equity Ownership. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding.

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Chronic Exposure to Cytoreductive Treatment Shapes Clonal Evolution in Myeloproliferative Neoplasms

Blood ◽

10.1182/blood-2021-152622 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3620-3620

Author(s):

Lin-Pierre Zhao ◽

Nabih Maslah ◽

Rafael Daltro De Oliveira ◽

Emmanuelle Verger ◽

Juliette Soret-Dulphy ◽

...

Keyword(s):

Board Of Directors ◽

Mutation Rate ◽

Chronic Exposure ◽

Research Funding ◽

Myeloproliferative Neoplasms ◽

Clonal Evolution ◽

Advisory Committees ◽

Cytoreductive Treatment ◽

The Impact

Abstract Introduction: Myeloproliferative neoplasms (MPN) are a heterogeneous group of chronic myeloid malignancies resulting from the combination of a driver mutated gene (JAK2, MPL or CALR) and a variety of acquired additional somatic mutations. Although next-generation sequencing (NGS) has identified high molecular risk mutations associated with adverse prognosis (Vannucchi et al., Leukemia, 2013 , Guglielmelli et al., Leukemia, 2014 ), the clonal evolution of these mutations remains poorly described. Chronic exposure to cytoreductive treatment, especially genotoxic drugs such as hydroxyurea (HU), could impact clonal evolution. A previous study suggested that Interferon-α (IFN) could limit the accumulation of cytogenetic abnormalities compared to HU (Mondello et al., Blood, 2018). The objective of our study was to describe the long-term evolution of the mutational landscape in the era of NGS in a large cohort of MPN patients. Methods: A total of 1538 consecutive patients were diagnosed with MPN according to WHO criteria and followed in our hospital between January 2011 and January 2021. This study included 1039 of them in whom a NGS molecular analysis targeting 36 myeloid genes with a sensitivity of 1% was performed at diagnosis and/or during follow-up. Patients with only one NGS (n=588), AML/MDS transformation at either the first (n=3) or the second NGS (n=2) were excluded from the analysis. Serial NGS data obtained in chronic MPN phase were thus analyzed for 446 patients. Clinical and biological characteristics at time of diagnosis and follow-up were collected from medical charts and electronic medical records. Mutation rates per year were calculated for each gene as the difference in the number of mutations between first and last NGS divided by the time interval (in years) between both NGS. Results : Median age at MPN diagnosis in our whole cohort was 51 years [IQR 41-60]. Our cohort included 167 (37%), 205 (46%) and 64 (14%) patients with Polycythemia Vera (PV), Essential thrombocythemia (ET) and primary myelofibrosis (MF) respectively. 279 patients (63%) had at least one additional mutation at first NGS, and respectively 27 (6%) and 104 (23%) patients had TP53 and high molecular risk mutations. Median interval between MPN diagnosis and the first NGS was 6.5 years [IQR 1.7-13] while median time between the first and the last NGS was 2.5 years [IQR 1.6-4, range 0.3-14.3]. Overall, 178 patients (39.9%) acquired an additional mutation at last NGS evaluation, most frequently involving TET2, DNMT3A, ASXL1, TP53 and NFE2 genes . To study the impact of chronic MPN therapy on clonal evolution, we focused on patients who electively received HU (n=112) or IFN (n=92) as a monotherapy, or did not receive any cytoreductive treatment (n=119) between the first and the last NGS. The remaining patients received ruxolitinib (n=44), anagrelide (n=10), vercyte (n=7) or polytherapy (n=62). At last follow-up, 74 patients receiving IFN (80.4%) and 65 (58%) treated with HU had a complete hematological response. When combining all additional mutations, the global mutation rate per year did not significantly differ between treatment groups. When analyzing individual genes, TP53 mutation rate was higher in patients treated with HU compared to the patients receiving IFN (p=0.014) or not treated (p=0.008) (Figure). MDS/AML evolution occurred in 4 patients (3.6%) treated with HU, 2 (1.7%) without cytoreductive therapy versus none of the 92 patients treated with IFN (ns). In the whole cohort, MDS/AML evolution was significantly increased in patients harboring TP53 mutations (p= 0.004). In contrast, DNMT3A mutation rate was significantly increased in patients receiving IFN compared to patients treated with HU (p=0.045) (Figure). The latest result is in line with previous observations showing that loss of DNMT3A could confer resistance to IFN in a JAK2-V617F mouse model (Stetka et al., Blood, 2020). Conclusion: Our results highlight the impact of chronic cytoreductive therapy on clonal evolution shaping in MPN. IFN limits the emergence of TP53 mutated clones compared to HU, thus potentially reducing the risk of leukemogenesis. Emergence of DNMT3A mutated clones under IFN therapy requires further exploration and could potentially play a role in therapeutic resistance. This study on a large clinically and biologically annotated cohort illustrates how serial NGS analysis may guide therapeutic options for MPN patients. Figure 1 Figure 1. Disclosures Raffoux: PFIZER: Consultancy; ASTELLAS: Consultancy; ABBVIE: Consultancy; CELGENE/BMS: Consultancy. Kiladjian: AbbVie: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Taiho Oncology, Inc.: Research Funding; PharmaEssentia: Other: Personal fees. Benajiba: Pfizer: Research Funding; Gilead: Research Funding.

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Long-Term Survival in Adult Patients with Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL) Who Achieved Minimal Residual Disease (MRD) Response Following Anti-CD19 BiTE® Blinatumomab

Blood ◽

10.1182/blood.v124.21.2287.2287 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2287-2287 ◽

Cited By ~ 4

Author(s):

Gerhard Zugmaier ◽

Nicola Goekbuget ◽

Andreas Viardot ◽

Matthias Stelljes ◽

Svenja Neumann ◽

...

Keyword(s):

Bone Marrow ◽

Board Of Directors ◽

Research Funding ◽

Residual Disease ◽

Advisory Committees ◽

Term Survival ◽

Long Term Survival ◽

Equity Ownership

Abstract Introduction: Relapsed/refractory (r/r) B-precursor ALL in adults has an unfavorable prognosis with a median overall survival of 4–8 months and a 5-year survival of <10%. Long-term follow-up data are presented from an exploratory phase 2 study with blinatumomab, an investigational bispecific T-cell engager (BiTE®) antibody construct that directs cytotoxic T-cells to CD19-expressing target cells (Topp MS et al. Blood 2012;120(21):670). Methods: The primary endpoint was hematologic complete remission (CR) or CR with partial hematologic recovery (CRh*) within 2 cycles of blinatumomab. Secondary endpoints included rate of minimal residual disease (MRD) response (defined as < 10-4), overall survival (OS), and relapse-free survival (RFS). Blinatumomab was administered by continuous intravenous infusion for 28 days followed by a 14-day treatment-free interval. Responding patients had the option to receive 3 additional cycles of treatment or to proceed to allogeneic hematopoietic stem cell transplantation (aHSCT). Results: 36 patients were treated; 25 (69%) responded, with 15 (42%) achieving CR and 10 (28%) CRh*. MRD response was achieved in 22 (88%) of these 25 patients with CR or CRh*. Thirteen patients with CR or CRh* proceeded to aHSCT after blinatumomab treatment. In addition, one patient with hypocellular bone marrow and MRD response after the first cycle underwent aHSCT. Follow-up for RFS is 22.4 months; median RFS is 8.8 months. Median follow-up for OS is 30.2 months; median OS is 12.9 months. Ten patients (28%) are alive at 29.7 months (Figure). We analyzed the characteristics of the 10 living long-term survivors, defined as OS of 2 years or longer, seven of whom were relapse-free. The age of these 10 patients at the time of first infusion ranged from 21 to 72 years; the blast count at screening ranged from 8% to 97% (median, 56%). Four of the 10 patients alive had received aHSCT prior to blinatumomab treatment. Of the six patients without a prior aHSCT, two were primary refractory; two had the first relapse within 12 months and two after 12 months post first diagnosis. In the 10 surviving patients blinatumomab treatment induced CR in seven patients, CRh* in two patients, and blast-free hypo-cellular bone marrow in one patient. All 10 surviving patients had an MRD response following blinatumomab treatment. The patient with hypocellular bone marrow received a transplant after the first cycle before potential recovery of blood counts qualifying for CR/CRh* could occur. Seven of the surviving patients underwent aHSCT after blinatumomab, including four patients who received a second aHSCT after they had already received an aHSCT prior to blinatumomab. One of the three patients who did not undergo aHSCT after CRh* had grade 4 cytokine release syndrome requiring resuscitation after 1 day of blinatumomab treatment and has remained in ongoing remission for 22 months without any further treatment aside from 5 cycles of blinatumomab. Another one of these three patients, who had a grade 3 neurologic event on day 2 of cycle 2, has remained in ongoing remission for 34 months without any further treatment aside from 5 cycles of blinatumomab. The third of these three patients had two CD19-positive relapses after CR following blinatumomab treatment. The patient was retreated with 3 cycles of blinatumomab, resulting twice in CR and MRD response. Two of the 10 surviving patients relapsed after blinatumomab and aHSCT; one patient with a CD 19-negative relapse achieved another hematologic remission by chemotherapy. Summary: These data show that patients with r/r ALL, who achieved MRD response and received subsequent aHSCT following blinatumomab immunotherapy may achieve long-term survival longer than 2 years. Studies with a larger sample size are warranted to confirm these data. Two patients with grade 3 or 4 toxicities showed long-term survival without aHSCT after blinatumomab. Figure Figure. Disclosures Zugmaier: Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Off Label Use: This presentation will discuss the off-label use of blinatumomab, as this agent is not approved for use by the FDA, EMA or any other regulatory authorities.. Goekbuget:Amgen Inc.: Consultancy, Honoraria, Research Funding. Viardot:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Travel support Other; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Travel support, Travel support Other; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Travel support Other. Horst:Amgen Inc.: Honoraria, Research Funding. Brueggemann:Amgen Inc.: Consultancy, Research Funding. Holland:Amgen Inc.: Employment, Equity Ownership. Schmidt:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Mergen:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Bargou:Amgen Inc.: Consultancy, Honoraria. Topp:Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Evaluation of All Cause of Death after High Dose Chemotherapy and Autologous Stem Cell Transplant in Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood-2018-99-118896 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2157-2157

Author(s):

Danielle Roberts ◽

Subir Goyal ◽

Zhao Chang ◽

Christopher R Flowers ◽

Mary Jo Lechowicz ◽

...

Keyword(s):

Board Of Directors ◽

Hodgkin Lymphoma ◽

Organ Dysfunction ◽

Cause Of Death ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Advisory Committees ◽

Time To Death

Abstract Background High dose chemotherapy and autologous stem cell transplant (ASCT) results in cure for up to 50% of patients with Hodgkin (HL) and aggressive non-Hodgkin lymphoma (NHL) that relapse after initial treatment with chemo-immunotherapy. Despite improvements in supportive care and patient selection, death after ASCT remains a concern due to progressive disease, infection, and other treatment- and non-treatment-related causes. We evaluated causes and predictors of death in patients undergoing ASCT for HL and NHL. Methods We conducted a single-institution, retrospective study of all patients with HL and NHL including diffuse large B-cell lymphoma, high grade B-cell lymphoma NOS, follicular lymphoma, Burkitt lymphoma, marginal zone lymphoma, and T-Cell lymphoma who underwent ASCT at Emory University between January 1, 2006 and June 1, 2017. We evaluated each patient with regards to pre-transplant disease and other baseline characteristics, treatment response after ASCT, occurrence of relapse post-ASCT, post-ASCT death and cause of death. Among patients who died, we compared baseline characteristics of interest between groups based on the documented cause of death using Fisher's Exact tests and t-tests. The association between cause of death and time to death from ASCT was evaluated by the Kruskal-Wallis test. Box plots were used to describe time to death post-transplant. Results Of 642 patients completing ASCT, 192 died during the period of observation after a median follow-up of 24 months. Among patients who died, the leading causes of death were relapsed disease (n=136, 71%), infection (n=18, 9%), organ dysfunction (n=16, 8%), secondary malignancy (n=8, 4%), and other/unspecified (n-14, 7%). When the group was divided into disease-related (n=136) vs non-disease-related death (n=56), none of the pre-specified variables of interest including age, gender, disease status at transplant, stage, induction or salvage therapy, conditioning regimen, or KPS were significantly associated with disease- vs non-disease-related death. Of the 18 deaths due to infection 7 were due to bacterial sepsis (including 5 prior to day +30 post ASCT), 3 were due to fungal infections, 3 were due to pneumonia, 1 death each was due to hepatitis C, nocardia, pneumocystis jirovecii, cytomegalovirus, and C. Difficile. The median time to death for patients experiencing infection or organ dysfunction was 0.5 years each compared to 1 year for patients dying of disease relapse and 4 years for patients experiencing a secondary malignancy (p<0.001; See Figure). Conclusions Among patients completing ASCT for HL or NHL, most deaths occurred due to relapse of the primary disease. There were no significant associations with baseline or treatment-related variables with the cause of death. The median time to death for patients with infection or organ dysfunction was 0.5 years, suggesting that continued monitoring and supportive care of patients completing ASCT is required beyond the initial engraftment period. Our findings support the role of intensive follow-up during the first year post- ASCT and continued monitoring for long-term toxicities for subsequent years of follow-up. Figure Figure. Disclosures Roberts: AstraZeneca: Consultancy. Flowers:Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Gilead: Research Funding; Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; OptumRx: Consultancy; Genentech/Roche: Research Funding; Janssen Pharmaceutical: Research Funding; Celgene: Research Funding; Millennium/Takeda: Research Funding; Pharmacyclics: Research Funding; Abbvie: Consultancy, Research Funding; Gilead: Consultancy; Karyopharm: Consultancy; Pharmacyclics/ Janssen: Consultancy; TG Therapeutics: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Abbvie: Research Funding; Spectrum: Consultancy; Genentech/Roche: Consultancy; Denovo Biopharma: Consultancy; Bayer: Consultancy. Waller:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celldex: Research Funding; Kalytera: Consultancy; Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Cambium Medical Technologies: Consultancy, Equity Ownership. Lonial:Amgen: Research Funding. Allen:Merck: Research Funding; Bayer: Consultancy. Blum:Morphosys: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding. Kaufman:Roche: Consultancy; Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Janssen: Consultancy; BMS: Consultancy. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Bristol-Myers Squibb: Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: 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, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Takeda: Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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