Clinical Analysis of Immunodeficiency-Associated Lymphoproliferative Disorders in a Single Institution

Abstract Background Recent progress in medicine faces more patients to iatrogenic immunosuppressive state, which increases the risk of following immunodeficiency-associated lymphoproliferative disorders (LPD), such as post-transplant lymphoproliferative disorders (PTLD) which arise after solid organ or hematopoietic stem cell transplantation (HSCT), and other lymphoid proliferations or lymphomas which arise in patients treated with immunosuppressive agents for any reasons. Methotrexate for patients with rheumatoid arthritis (RA) has been the most discussed immunosuppressive agent associated with iatrogenic LPD. Nevertheless, the number of patients treated with other immunosuppressive agents such as biological response modifiers for RA and calcineurin inhibitors after HSCT has recently increased and clinical assessment of iatrogenic-LPD under this recent immunosuppressive setting is still limited. Clinical prognostic factors remain controversial due to the heterogeneity of this disease concept, patients' background and treatment. Methods: A total of 71 patients diagnosed as iatrogenic immunodeficiency-associated lymphoproliferative disorders (PTLD, n=26; other LPD, n=45) over last 20 years in Kyoto University Hospital were reviewed. Cox regression analysis was used to examine the impact of patient characteristics including immunological backgrounds and tumor status on outcomes. Results: Median age at diagnosis of LPD was 63 (range, 3-83; PTLD, 50; other LPD, 66). Regarding the PTLD patients, 12 were recipients of liver transplantation, 8 were of HSCT, 4 were of lung and 2 were of kidney transplantation. Background diseases of the other LPD were RA in 43, systemic lupus erythematosus in 1 and systemic sclerosis in 1. Median time from the initiation of immunosuppressive agents to LPD diagnosis was 82 months (range, 1.5-348.5; PTLD, 35.4; other LPD, 116.5). The number of immunosuppressive agents given at LPD diagnosis was 0 in 1 patient, 1 in 14, 2 in 42, 3 in 12 and 4 in 1 patient. Twenty-nine percentage of those receiving multiple immunosuppressive agents were administered methotrexate in combination with PSL or biological response modifiers. Ann Arbor stage at diagnosis was I in 8 patients, II in 13, III in 20 and IV in 28 patients. Histologic subtypes of PTLD were monomorphic (n=19), polymorphic (n=4), and non-destructive PTLD (n=3). Pathological diagnosis of other LPD were DLBCL (n=20), polymorphic LPD (n=5), classical Hodgkin lymphoma (n=6), Hodgkin-like lesion (n=3), Burkitt lymphoma (n=1), EBV-positive mucocutaneous ulcer (n=3), and other B-cell lymphomas (n=7). EBER in situ hybridization was positive in 38 (63.3%) and systemic EBV reactivation was detected in 17 (43.6%).First line therapy included reduction of immunosuppressive agents without chemotherapy in 33 patients (PTLD, n=4; other LPD, n=29), RTX-containing chemotherapy in 23 (PTLD, n=14; other LPD, n=9), other chemotherapies in 7 (PTLD, n=4; other LPD, n=3), radiation therapy in 2, and no additional treatment in 2 patients.After the first line therapy, complete remission was achieved in 35 patients, partial response in 13, and stable or progressive disease in 14. A total of 4 patients died during the first line therapy. Five-year survival rate was 49.9% (PTLD, 39.0%; other LPD, 54.0%; P=0.101).Multivariate analysis showed that low number of lymphocyte count (< 890/µl, median lymphocyte count) at diagnosis (HR, 5.55; P=0.013), hypoalbuminemia (serum albumin value <3.2 g/dl) at diagnosis (HR, 6.36; P=0.015) and higher IPI (high-risk group vs others, HR, 2.71; n=0.021) were risk factors for poor prognosis. In subgroup analysis for PTLD, low IgG (<825 mg/dl, lowest limiting value of our center) was also an independent prognostic factor for inferior outcome (HR, 15.5; P=0.011). Conclusions: Overall survival of immunodeficiency-associated lymphoproliferative disorders under recent immunosuppressive settings, especially PTLD, was still poor. We found that low number of lymphocyte count could be a new risk factor for poor prognosis, along with known factors as IPI and hypoalbuminemia. Low IgG value was also suggested to be a prognostic factor for inferior outcome in PTLD patients. Figure. Figure. Disclosures Nishikori: Eisai: Research Funding; Ono Pharmaceuticals: Research Funding.

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Bortezomib Overcomes Poor Prognosis Conferred By High Sictp in Untreated Plasma Cell Disorders

Blood ◽

10.1182/blood-2019-129324 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5492-5492

Author(s):

Akira Honda ◽

Yu Oyama ◽

Kazuhiro Toyama ◽

Mineo Kurokawa

Keyword(s):

Pharmaceutical Company ◽

Plasma Cell ◽

Research Funding ◽

Poor Prognosis ◽

Proteasome Inhibitors ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Plasma Cell Disorder ◽

Cell Disorder

Introduction To date, various biochemical markers of bone remodeling have been investigated in multiple myeloma (MM) patients. Serum C-terminal telopeptide of type I collagen (sICTP) is a well-known biochemical marker of bone remodeling. Although several reports showed the relationship between a high level of sICTP and poor prognosis in MM patients, little is known about the efficacy of bortezomib in high sICTP patients. In this single center retrospective study, we assessed the association between sICTP and the prognosis of plasma cell disorder patients, particularly in patients firstly treated with bortezomib-containing regimen. Methods We retrospectively reviewed untreated MM and other plasma cell disorder patients who were diagnosed at The University of Tokyo Hospital between January 2001 and December 2016. The clinical data of patients whose sICTP was measured before the start of first-line therapy were collected. Serum ICTP was measured at diagnosis in 59 patients: 56 patients with MM, 2 patients with plasmacytoma, and 1 patient with light chain amyloidosis. These patients were divided into high sICTP and low sICTP groups according to the median of sICTP level. Additionally, patients firstly treated with bortezomib-containing regimen were divided into two groups according to the median of sICTP level. Overall survival (OS) and bone fracture-free survival (FFS) were calculated from initiation of the first-line therapy using the Kaplan-Meier method and log-rank tests. Results In 59 patients, the median age was 65 years (range, 45-85 years) and median follow-up was 387 days (range, 22-2019 days). Thirty-three patients (55.9%) were male and 26 (44.1%) were female. IgG was the most frequent subtype of M-protein (58%), followed by IgA (19%), Bence Jones proteins (19%), and IgE (3%). International scoring system classified 16 (27.1%), 24 (40.7%), and 19 (32.2%) as stage I, II, and III, respectively. Levels of sICTP were high in 31 (52.5%) patients and low in 28 (47.4%) patients. The level of sICTP differed significantly (P<0.01) between the groups ISS stage I, II, and III, and increased parallel with the progression of the disease. Twenty-eight (47.4%) patients were administered bortezomib-containing regimen as first-line therapy, which was consisted of BD (bortezomib + dexamethasone), VCD (bortezomib + cyclophosphamide + dexamethasone), and VMP (bortezomib + melphalan + prednisolone). The remaining 31 (52.5%) patients were administered without proteasome inhibitors as first-line therapy. Nineteen patients (32.2%) achieved at least very good partial response after first-line therapy and 9 (15%) patients fractured after start of first-line therapy. Median OS for the entire cohort was 1874 days. In the Kaplan-Meier survival analysis, high sICTP (above upper limit: 6.0 mg/l) significantly associated with worse 2-year OS (63% versus 96%, P=0.02) and worse 2-year FFS (51% versus 86%, P=0.04). Serum ICTP may be a useful marker to predict survival and future bone fracture in our cohort, and these results are consistent with previous reports. Interestingly, in the patients firstly treated with bortezomib-containing regimen, the level of sICTP had no effect on 2-year FFS (90% with high sICTP versus 100% with low sICTP, P=0.53) and 2-year OS (95% with high sICTP versus 100% with low sICTP, P=1). Conclusion In general, high sICTP is considered to be a poor prognostic factor in MM patients, and similar results were also demonstrated in our cohort. Importantly, our data suggest that bortezomib may overcome poor prognosis conferred by high sICTP in plasma cell disorder patients. Further studies based on more cases are warranted to elucidate the efficacy of bortezomib in high sICTP patients. In addition, further studies on other proteasome inhibitors, such as carfilzomib or ixazomib are also needed. Disclosures Honda: Hitachi, Ltd.: Speakers Bureau. Toyama:Bristol-Myers Squibb: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Celgene K.K.: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau. Kurokawa:Shire Japan K.K.: Speakers Bureau; Novartis Pharma K.K.: Research Funding; Daiichi Sankyo Conpany: Speakers Bureau; Pfizer Japan Inc.: Research Funding; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Celgene K.K.: Consultancy, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co.,Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Yakult Honsha Company: Speakers Bureau; Bioverativ Japan ltd.: Consultancy; Chugai Pharmaceutical Company: Consultancy, Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; MSD K.K.: Consultancy, Research Funding, Speakers Bureau; Shionogi & Co., Ltd: Consultancy, Honoraria; Teijin Limited: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Janssen Pharmaceutical K.K.: Speakers Bureau.

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Lenalidomide Treatment For Lower Risk Non-Deletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Prior To Azanucleosides

Blood ◽

10.1182/blood.v122.21.1507.1507 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1507-1507

Author(s):

Rami S Komrokji ◽

Maria G. Corrales-Yepez ◽

Najla H Al Ali ◽

Eric Padron ◽

Jeffrey E Lancet ◽

...

Keyword(s):

Overall Survival ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Research Funding ◽

Response Rates ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

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The Prognostic Value of IgH Clonality in Bone Marrow with Negative Pathology in B Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-114628 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5298-5298

Author(s):

Kazuhiro Toyama ◽

Ayato Tsukamoto ◽

Sho Yamazaki ◽

Fumihiko Nakamura ◽

Mineo Kurokawa

Keyword(s):

Bone Marrow ◽

Prognostic Factor ◽

B Cell ◽

Research Funding ◽

Bone Marrow Involvement ◽

Pharmaceutical Research ◽

Complete Response ◽

Pathological Examination ◽

First Line ◽

First Line Therapy

Abstract Background Bone marrow infiltration is widely accepted as an important prognostic factor in malignant lymphomas. Although multiplex polymerase chain reaction for the detection of clonal immunoglobulin heavy chain (IgH) gene rearrangements is a helpful tool for the confirmation of minimal infiltration in B cell lymphomas, it has not been elucidated that IgH clonality of the bone marrow at the initial evaluation is a valuable prognostic factor and a predicting marker for the initial therapy in the patients with B cell lymphomas who had a bone marrow biopsy with negative pathology. Methods All patients with DLBCL (n=61) and indolent B cell non-Hodgkin's lymphomas (iB-NHL) including FL, MCL and MALT lymphoma (n=51) who had a bone marrow biopsy and a bone marrow IgH clonality obtained at diagnosis in our institute it the period between March 2002 and 2016 were included in this study. The clinical information including the overall survival (OS), progression free survival (PFS), laboratory findings, backgrounds, and the response to the first line therapy were collected from the clinical charts. Result Bone marrow infiltration by pathological examination was reported in 20% (12/61) of DLBCL patients and in 24% (12/51) of iB-NHL patients (Path-pos group). In the patients with negative pathological report, 21% of the DLBCL patients (13/61) and 33% of the iB-NHL patients (17/51) were positive bone marrow involvement by PCR (Path-neg/PCR-pos group). The other 59% of the DLBCL patients (36/61) and 43% of the iB-NHL patients (22/51) were negative bone marrow involvement by both pathological examination and PCR (Path-neg/PCR-neg group). In DLBCL cohort, the 5-year OS rates in Path-pos, Path-neg/ PCR-pos, and Path-neg/ PCR-neg groups were 46.9% (95% CI, 13.2% to 75.3%), 92.3% (95% CI, 56.6% to 98.9%), and 85.5% (95% CI, 68.7% to 93.7%), respectively (p=0.0735). The 5-year PFS rates in Path-pos, Path-neg/PCR-pos, and Path-neg/PCR-neg group were 33.3% (95% CI, 10.3% to 58.8%), 76.9% (95% CI, 44.2% to 91.9%), and 71.1% (95% CI, 52.9% to 83.3%), respectively (p=0.0331). There were no significant difference between Path-neg/ PCR-pos group and Path-neg/ PCR-neg group in the 5-year OS and PFS rates (p=0.698). In DLBCL patients, the positivity of pathological examination of bone marrow was identified as a valuable prognostic factor, but the positivity of PCR was not a prognostic factor. In iB-NHL cohort, the 5-year OS rates in Path-pos, Path-neg/PCR-pos, and Path-neg/PCR-neg groups were 77.5% (95% CI, 44.8% to 92.3%), 100% (95% CI, 100% to 100%), and 94.4% (95% CI, 66.6% to 99.2%), respectively (p=0.114). The 5-year PFS rates in Path-pos, Path-neg/PCR-pos, and Path-neg/PCR-neg group were 45.7% (95% CI, 17.3% to 70.5%), 46.8% (95% CI, 19.6% to 70.2%), and 87.1% (95% CI, 57.3% to 96.6%), respectively (p=0.152). There were almost no difference between Path-pos, Path-neg/PCR-pos, and Path-neg/PCR-neg group in the 5-year OS rate, but the 5-year PFS rate in Path-pos and Path-neg/PCR-pos group tend to be lower than in Path-neg/PCR-neg group (p=0.0641 and p=0.0891, respectively). In iB-NHL cohort, in addition to the positivity of pathological examination, the positivity of PCR is possible to be a prognostic factor. Univariate analysis of PFS in pathology negative patients in iB-NHL revealed that performance status was a significant prognostic factor, and IgH clonality also seemed to be a prognostic factor. Multivariate analysis of PFS in pathology negative patients in iB-NHL showed that there was no significant independent risk factor. In the response to the first line therapy in DLBCL cohort, the rate of complete response in Path-pos, Path-neg/PCR-pos, and Path-neg/PCR-neg groups were 83.3%, 90.9%, and 80.0%, respectively (p=0.8871). In iB-NHL cohort, the rate of complete response were 60.0%, 71.4%, and 82.4%, respectively (p=0.4623). In each cohort, there were no difference between each groups in overall response rate and complete response rate. Conclusion Positive IgH clonality with negative pathology in bone marrow is a valuable prognostic factor for PFS at diagnosis in the patients with iB-NHL. Disclosures Kurokawa: Eizai: Research Funding; MSD: Honoraria, Research Funding; Chugai Pharmaceutical: Research Funding; Teijin Pharma: Research Funding; Takeda Pharmaceutical: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Astellas Pharma: Research Funding; Sumitomo Dainippon Pharma: Research Funding; Nippon Sinyaku: Honoraria, Research Funding; Otsuka Pharmaceutical: Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding.

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Outcomes of Plasma Cell Leukemia Patients in the Era of Next-Generation Novel Agents: A Single-Center Retrospective Cohort Study

Blood ◽

10.1182/blood-2020-141525 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 6-7

Author(s):

Alex Ge ◽

Chiung-Yu Huang ◽

Thomas Martin ◽

Jeffrey L. Wolf ◽

Nina Shah ◽

...

Keyword(s):

Plasma Cell ◽

Research Funding ◽

Progression Free Survival ◽

Novel Agents ◽

Next Generation ◽

First Line ◽

Advisory Committees ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy

Introduction Primary plasma cell leukemia (pPCL) is a rare and aggressive disease comprising 1-5% of all plasma cell dyscrasias. Although historically pPCL has been defined by circulating plasma cells (CPCs) ≥ 20% and 2.0 × 109/L, many series require only one of these two criteria for diagnosis. Over time there has been a pressing need to change the definition further in order to capture patients at an earlier stage of the disease. Recent studies have shown that multiple myeloma (MM) patients who have CPCs ≥ 5% but < 20% at diagnosis have similarly poor outcomes. These thresholds for defining pPCL have not been studied in the current era of novel agents. While bortezomib-based regimens have been shown to extend pPCL patient survival, studies with next-generation agents such as carfilzomib (CFZ), pomalidomide, and daratumumab (DARA) are still scarce. Methods We performed a single-center, retrospective study of patients who at diagnosis had pPCL (defined as CPCs ≥ 20% or 2.0 × 109/L) or had MM with < 20% CPCs (MM-CPC). Patients were treated at our institution between 1/1/2000-7/17/2020. Overall response rates were determined according to International Myeloma Working Group criteria. Overall survival (OS) was defined as the length of time between initiation of first line therapy and death. Progression-free survival (PFS) was defined as the length of time between initiation of first line therapy and first progression. OS and PFS were compared using log-rank tests. Results Of the 54 patients identified, 38 had pPCL and 16 had MM-CPC. The median age at diagnosis of the pPCL and MM-CPC groups were 59.2 (range 43-94) and 59.8 years (range 29-79), respectively, with a similar percentage of females, 47.4% vs. 37.5%. Both groups were similarly distributed by year of diagnosis; 76.3% and 62.5% of pPCL and MM-CPC patients were diagnosed between 2012-2020, respectively. The pPCL cohort had median CPCs of 40% (15-98) while the MM-CPC cohort had median CPCs of 4% (1-15). Median CPCs at diagnosis was 3.36 (0.44-179) × 109/L in the pPCL group compared to 0.33 (0.04-1.79) × 109/L in the MM-CPC group. Most patients for both groups were ISS stage III at diagnosis (57.9% in pPCL cohort, 56.2% in MM-CPC cohort). R-ISS assessment was not feasible due to missing data. A greater proportion of patients in the pPCL group (44.7%) had complex cytogenetics at diagnosis compared to the MM-CPC group (25.0%). All patients were exposed to at least one novel agent over the entire disease course. Of these patients, 50 (92.6%) were exposed to bortezomib, 45 (83.3%) to lenalidomide, 33 (61.1%) to CFZ, 22 (40.7%) to DARA, 13 (24.1%) to pomalidomide, and 4 (7.4%) to venetoclax. Twenty-four patients (44.4%) received an autologous stem cell transplant (ASCT). At the best response to treatment, 76.7%, 62.8% and 37.9% of patients achieved a partial response or greater to first, second and third line therapy, respectively. The median OS of the pPCL and MM-CPC groups was 34.5 and 35.5 months (p = 0.97) (Figure 1A), while the median PFS was 13.9 and 10.9 months (p = 0.52) (Figure 1B), respectively. The median follow-up was 28.1 months. No differences were observed for patients with CPCs < 20% compared to patients with CPCs ≥ 20% (p = 0.98). There was trend towards a better survival for patients with CPCs < 2 × 109/L compared to CPCs ≥ 2 × 109/L (p = 0.35). Since we did not observe any meaningful difference in OS or PFS between the pPCL and MM-CPC groups, we combined these groups for further survival analysis. Patients exposed to either DARA or CFZ (n = 37) had a median OS of 59.2 months, while patients exposed to neither drug (n = 17) had a median OS of 11.7 months (p = 0.02) (Figure 1C). ASCT was associated with a prolonged median OS (66.8 months vs. 17.2 months, p = 0.0001) (Figure 1D), while a complex karyotype at diagnosis was associated with a poorer median OS (17.4 months vs. 66.8 months, p = 0.01). Conclusions In the era of next-generation novel agents, overall and progression-free survival of pPCL and MM-CPC patients are similar. Patients exposed to DARA or CFZ have an improved survival compared to those who did not receive these drugs. ASCT is also associated with a superior survival over those who did not receive a transplant. Further studies are needed to evaluate the efficacy of these next-generation drugs in this patient population. Disclosures Martin: Janssen: Research Funding; Seattle Genetics: Research Funding; AMGEN: Research Funding; GSK: Consultancy; Sanofi: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Wong:Sanofi: Membership on an entity's Board of Directors or advisory committees; Fortis: Research Funding; Roche: Research Funding; Janssen: Research Funding; Amgen: Consultancy; GSK: Research Funding; Bristol Myers Squibb: Research Funding.

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Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽

10.1182/blood-2019-127237 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5880-5880

Author(s):

Nathan H Fowler ◽

Yanni Hao ◽

Stephen Lim ◽

Guifang Chen ◽

Frank Li ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Third Line ◽

Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

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Optimizing Deep Response Assessment for AL Amyloidosis Using Involved Free Light Chain Level at End of Therapy

Blood ◽

10.1182/blood-2018-99-113958 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3227-3227

Author(s):

Eli Muchtar ◽

Angela Dispenzieri ◽

Nelson Leung ◽

Francis K. Buadi ◽

David Dingli ◽

...

Keyword(s):

Board Of Directors ◽

Light Chain ◽

Research Funding ◽

Response Assessment ◽

Al Amyloidosis ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Organ Response

Abstract Introduction: Light chain burden in light chain (AL) amyloidosis is often low, making accurate response assessment challenging. Methods: AL amyloidosis patients achieving very good partial or complete response to first line therapy and had serial sFLC studies during and after completion of therapy were included (n=396). Involved free light chain (iFLC), difference in involved-to-uninvolved free light chains (dFLC) and sFLC ratio (sFLCR) were assessed at the end of first line therapy and at nadir iFLC. Survival analysis was done using the Kaplan-Meier method. Hematological progression-free survival (hemPFS) was defined as the time from diagnosis until hematological progression or death, where patients known to be alive and progression-free at the end of follow-up were censored. Hematological progression was defined according to consensus criteria or upon initiation of second line therapy, whichever came first. Results: The median iFLC and dFLC at the end of therapy was 1.7 mg/dL and 0.5 mg/dL, respectively. sFLCR normalization occurred in 70% of patients. iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL were associated with a longer hemPFS compared to their counterparts (Figure). Only iFLC ≤2 mg/dL was associated with a significantly longer overall survival (Figure). sFLCR normalization did not predict hemPFS or overall survival. Organ response was predicted by iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL (Table), with best discrimination seen with iFLC ≤2 mg/dL. Organ response was not predicted by sFLC normalization (Table). The median nadir iFLC was 1.4 mg/dL and was reached 3.9 months from the end of therapy, longer in transplanted patients compared to patients treated with non-transplant regimens (7.3 vs 1.8 months, respectively; P<0.001). iFLC ≤2 mg/dL at the completion of therapy and nadir iFLC reached >12 months from the end of therapy were favorable predictors of hemPFS/OS in a multivariate analysis. Conclusion: iFLC at the end of first line therapy better predicts for organ response and survival than dFLC among deep responders. Normalization of sFLCR does not predict for organ response or survival and should not be used as measure of therapeutic efficacy. Figure. Figure. Disclosures Dispenzieri: Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; 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. Kapoor:Celgene: Research Funding; Takeda: Research Funding. Russell:Vyriad: Equity Ownership. Kumar: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; 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. Gertz:Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Abbvie: Consultancy; annexon: Consultancy; janssen: Consultancy; spectrum: Consultancy, Honoraria; Research to Practice: Consultancy; Medscape: Consultancy; Apellis: Consultancy; Teva: Consultancy; Amgen: Consultancy; Prothena: Honoraria; Physicians Education Resource: Consultancy.

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Functional Cure, Defined As PFS of More Than 7 Years, Is Achieved in 9% of Myeloma Patients in the Era of Conventional Chemotherapy and of First-Generation Novel Anti-Myeloma Agents; A Single-Center Experience over 20-Year Period

Blood ◽

10.1182/blood-2018-99-113108 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1968-1968

Author(s):

Evangelos Terpos ◽

Maria Roussou ◽

Ioannis Ntanasis-Stathopoulos ◽

Nikolaos Kanellias ◽

Despina Fotiou ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

First Generation ◽

Steering Committee ◽

First Line ◽

Conventional Chemotherapy ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Travel Grant

Abstract Advances in the management of multiple myeloma (MM) led to a significant prolongation of overall survival (OS), mainly of the younger patients; almost 10% of them experience more than 10-year OS. Although long progression-free survival (PFS) correlates with extended OS, there is very limited information for the characteristics of patients who manage to be progression-free for a long period after first-line therapy. The aim of this analysis was to evaluate the characteristics of patients who achieved at least 7-year of PFS after frontline therapy and compare them with those of all other patients who were treated in a single center during the same time period. Between January 1994 and December 2010, 406 consecutive newly diagnosed MM patients received first line therapy in the Department of Clinical Therapeutics (Athens, Greece). All patients had symptomatic disease, based on the IMWG criteria of that period (at least one CRAB symptom to start anti-myeloma therapy). Thirty-six (8.8%; 23M/13F) patients achieved a PFS of at least 7 years (long PFS group) after frontline treatment. The median PFS of these 36 patients is 10 years, while the other patients had a median PFS of 22 months. Long PFS patients were younger (median age 56 vs 68 years; p<0.001), had bigger body surface area (median: 1.85 m2 vs. 1.76 m2; p=0.013) and lower ECOG performance status (score 0-1: 71% vs 52%; p=0.014) compared to all others. Long PFS patients had higher hemoglobin (11.4 g/dl vs 10.2 g/dl; p=0.001), higher platelet count (278 vs 224 x109/l; p<0.001) and higher creatinine clearance (CrCl, based on the MDRD formula: 88 vs 67 ml/min; p<0.001; no patient in the long PFS group presented with CrCl <45 ml/min at diagnosis). There was no difference between the two groups regarding percentage of patients with high LDH, presence of osteolysis, type of myeloma (IgG vs IgA vs others), levels of serum and/or urine M-protein, and percentage of plasma cell infiltration in the bone marrow. However, more patients in the long PFS group had ISS-1 or ISS-2 disease (86% vs 61%; p=0.002) and normal pattern of marrow infiltration in the MRI of the spine and pelvis (24% vs 15%; p=0.035). Regarding chromosome abnormalities at diagnosis, no patient in the long PFS group had high-risk cytogenetics (defined as presence of del17p, t(4;14) or t(14;16) vs 32% in all other patients. All patients received either conventional chemotherapy (CC) or first-generation novel anti-myeloma agent (bortezomib (B), thalidomide (T) or lenalidomide (R)-based regimens as frontline therapy. There was no difference between the two groups regarding CC versus novel agent-based induction treatment. Out of 36 long-term PFS patients, 11 (30%) received CC, 8 (22%) B-based, 8 (22%) RD, 6 (17%) T-based, and 3 (8%) VTD; 10 (28%) patients received first-line therapy participating in a clinical trial. Long PFS patients had received more often autologous stem cell transplantation (ASCT, 61% vs 23%; p=0.001) as part of first line therapy; therefore, more long PFS patients had also received consolidation and/or maintenance (50% vs 15%; p=0.001). Higher proportion of patients achieved at least VGPR (74% vs 41%) or at least CR (32% vs 18%) in the long PFS group. We performed next generation flow cytometry in 23 patients of the long PFS group to evaluate minimal residual disease (MRD) and 14 (61%) of them were MRD (-) at the level of the 10-6. The probability of achieving long PFS (≥7 years) for patients who managed to be progression-free at 2, 3 and 4 years was 11.6%, 13.2% and 15.3%, respectively. In the multivariate analysis, only younger age was associated with probability for long PFS (p<0.001). The median OS of the whole group of patients was 5 years; in the long-PFS group median OS has not been reached yet while in all other patients the median OS was 4.3 years. In conclusion, our study in an unselected group of patients, the majority of whom did not participate in clinical trials, showed that 9% of patients with newly diagnosed myeloma experience prolonged PFS of more than 7 years (median: 10 years) even in the era of CC or first-generation novel agents. These patients have low risk disease, mainly of ISS-1 or -2, no high-risk cytogenetics, no or mild renal impairment, and achieve deep responses after ASCT. These patients may be considered as "functionally" cured. The incorporation of novel treatment approaches may lead to a significant improvement in the probability of achievement of this "functionally" cured status. Disclosures Terpos: Novartis: Consultancy; BMS: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding. Kastritis:Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria.

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Recombinant Interferon-α Reduces Thrombotic Events in Patients with Polycythemia Vera

Blood ◽

10.1182/blood-2019-131605 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1664-1664

Author(s):

Spencer Krichevsky ◽

Ghaith Abu Zeinah ◽

Claudia Sosner ◽

Diana Jaber ◽

Niamh Savage ◽

...

Keyword(s):

Research Funding ◽

Advisory Board ◽

Interferon Α ◽

First Year ◽

First Line ◽

Thrombotic Risk ◽

Vein Thrombosis ◽

First Line Therapy ◽

Line Therapy ◽

Thrombotic Complications

Introduction: Polycythemia vera (PV) is characterized by an increased red cell mass resulting in whole blood hyperviscosity, a strong predictor for thrombosis which remains a significant cause of morbidity and mortality1. Leukocytosis, thrombocytosis, and phlebotomy (PHL) rates are reported additive risk factors for thrombosis but their relative significance has been debated. PHL and cytoreductive therapy mitigates the risk of thrombotic complications. However, the relevance of these parameters remain insufficiently studied2,3. Our primary objectives were to assess the significance of these risks and their associations with thrombosis. We also evaluated whether first-line interferon-α (rIFNα), hydroxyurea (HU), and phlebotomy-only (PHL-O) therapy is associated with reduced thrombotic risk. Methods: After IRB approval, 328 patients (pts) were evaluated after diagnosis according to PVSG criteria (1974-2007), published Weill Cornell criteria (2008-2016)4, or WHO 2016 criteria. Demographics, clinical history, laboratory values, bone marrow findings, and genetic mutations were collected by querying our platform containing aggregated clinical data, the Observational Medical Outcomes Partnership Common Data Model5. Using intention-to-treat analysis, pts were assigned to a first-line therapy defined as continuous cytoreductive therapy for ≥1 consecutive year or PHL-O. Covariate differences between the first-line therapy groups at diagnosis were determined using χ2 tests for categorical variables. Overall survival (OS) was derived by the Kaplan-Meier estimator and comparisons of thrombosis risk were performed using a Cox proportional hazards model adjusted for clinically significant covariates such as age. Results: The characteristics of 165 men (50.3%) and 163 women (49.7%) with PV are shown in Table 1. Followup extended up to 45.0 years (yrs) with a median of 10.3 yrs. Median OS was 32.5 yrs. Splanchnic vein thrombosis, stroke, and deep vein thrombosis were the most common events. Median age at first event was 59.1 yrs. Predisposing factors associated with thrombosis included uncontrolled HCT, increasing leukocytosis, and ≥5 PHL during the first year after diagnosis. Elevated HCT was the greatest contributor to thrombosis: males with HCT of 53.0% had thrombotic complications at 10 times the rate of those with HCT of 43.5% and females with HCT of 51.9% had a thrombosis at 6 times the rate of those with HCT 40.0% (Fig 1). Pts with leukocytosis (30.8x109/L) had a thrombosis at 2.5 times the rate of those with a white blood cell (WBC) value of 9.4x109/L. There was a weak association between platelet (PLT) count and thrombosis (data not shown). The mean number of first-year PHL was 5.3±4.3; those pts requiring ≥5 had a thrombosis at 2 times the rate of those that required less (p=0.011). The difference in cumulative incidence of thrombotic events within 10 yrs was statistically significant for pts requiring ≥5 first-year PHL (p=0.031, Fig 2). There was a significant difference in the cumulative incidence of thrombosis during the first 10 yrs of diagnosis dependent on first-line therapy (PHL-O: n=117, HU: n=84, rIFNα: n=40) (p=0.021, Fig 3). The apparent superiority of IFN over HU and PHL in this retrospective study is suggested by 10 year cumulative incidences of thrombotic events of 3.2, 18.0, and 30.6%, respectively. Discussion: There was a significant correlation between HCT, WBC count, and PHL requirements, but not PLT count, with thrombotic events. Elevated HCT was the most important risk factor. However, leukocytosis and first-year PHL rates also contribute as indicated by the higher hazard ratios. This suggests a need for cytoreductive therapy from disease onset. Our analysis shows that rIFNα reduces thrombotic risk when compared to HU and PHL. Conclusion: Multivariate analysis indicates that elevated HCT level is the most important parameter for correlation with thrombosis within the first 10 yrs of illness. However, WBC and PHL rates are also significant. Since thrombosis occurs from the time of diagnosis, our data suggest the need for cytoreductive intervention from onset. Analysis of the three most common first-year therapies shows that HU and PHL are inferior to rIFNα in reducing thrombotic risk. Disclosures Ritchie: Celgene: Other: Advisory board; Pfizer: Other: Advisory board, travel support; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Genentech: Other: Advisory board; agios: Other: Advisory board; Tolero: Other: Advisory board; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Celgene, Incyte, Novartis, Pfizer: Consultancy. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Prospective biomarker validation trial evaluating the prognostic role of the combined expression of phospho-insulin growth factor receptor-1 and matrilysin in KRAS (exon 2) wild-type (WT) metastatic colorectal cancer (mCRC) patients treated with FOLFOX-6 plus panitumumab as first-line therapy [PULSE trial (GEMCAD 09-03)].

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.583 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 583-583

Author(s):

Juan Maurel ◽

Carlos Fernandez-Martos ◽

Marta Martin-Richard ◽

Vicente Alonso ◽

Jose Carlos Mendez ◽

...

Keyword(s):

Clinical Trial ◽

Poor Prognosis ◽

Growth Factor Receptor ◽

First Line ◽

Exon 2 ◽

Insulin Growth Factor ◽

First Line Therapy ◽

Line Therapy ◽

Insulin Growth Factor Receptor ◽

Kras Exon

583 Background: Matrilysin can activate phospho-insulin growth factor receptor-1 (pIGF-1R) through IGFBP-3 degradation, releasing IGF-1. Matrilysin per se has shown poor prognosis in mCRC and the co-expression of matrilysin and pIGF-1R (double positivity, DP) correlates with poor prognosis in WT KRAS refractory patients (pts) treated with anti-EGFR in retrospective analyses. We performed a prospective clinical trial in WT KRAS (exon 2) pts, treated with FOLFOX plus panitumumab in first-line therapy to validate those findings. Methods: Positive cases were defined by immunohistochemistry as those with moderate or strong intensity (++/+++) and > 70% expression for both matrilysin and p-IGF-1R (antibody anti-pY1316). The primary end-point was progression-free survival (PFS). Seventy-eight pts and 56 events were required to have an 80% power to detect a difference in median PFS of 6 months (two-sided p< 0.05). Results: We screened 196 mCRC pts in 24 centers between Nov/2010 and Apr/2013 and 78 pts met inclusion criteria (42 non-DP and 36 DP). Median follow-up was 23 months. There were no differences in baseline characteristics [age, sex, liver metastases, lactate dehydrogenase (LDH) levels, performance status and BRAF mutational status] between both groups. There were no differences in the number of FOLFOX-6 and panitumumab cycles received. Cutaneous toxicity was more frequent in DP pts (p = 0.035). Response rate was 80.5% in non-DP and 72.2% in DP patients (p = 0.37). Median PFS (95% CI) was 7.4 months (95%CI 5.2-13.3) in non-DP and 9.6 months (95% CI 6.7-17.5, p = 0.15) in DP patients. Median overall survival was 19.8 months (11.5-26.3) in non-DP pts and 39.1 months (26-NE, p = 0.071) in DP pts. Adjusted HR for PFS was 0.68 (95% CI 0.41-1.12). Adjusted analysis for OS was 0.50 (95% CI 0.27-0.90). Conclusions: We found that co-expression of matrilysin and pIGF-1R is a novel strong prognostic biomarker of survival benefit in mCRC KRAS WT pts treated in first-line with FOLFOX-6 plus panitumumab. Clinical trial information: NCT01288339.

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The Survival Outcome of the Patients with Relapsed/Refractory Anaplastic Large-Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.2738.2738 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2738-2738 ◽

Cited By ~ 1

Author(s):

Dai Chihara ◽

Michelle A. Fanale ◽

Mansoor Noorani ◽

Jason R Westin ◽

Loretta Nastoupil ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Cell Lymphoma ◽

Large Cell ◽

Survival Outcome ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Large Cell Lymphoma

Abstract Purpose: We assessed the survival outcome of patients with anaplastic large cell lymphoma (ALCL) who experienced disease progression or relapse after first line and subsequent therapy. We sought to evaluate the impact of brentuximab vedotin (BV), and survival outcome of patients with ALCL who experienced progression after BV. Patients and Methods: A total of 176 patients (74 ALK+, 102 ALK-) initially diagnosed between 1999 and 2014 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) after the progression/relapse following first-line chemotherapy (PFS1 and OS1), after first salvage therapy (PFS2 and OS2) and after second salvage therapy (PFS3 and OS3) were calculated. Outcome was separately analyzed according to the ALK status focusing on the use of BV. Results: The median age of the patients was 50 (range: 18-89). With a median follow up of 64 months, 111 patients (38 ALK+, 73 ALK-) experienced progression/relapse after the first-line therapy, of which 4 ALK- patients were post upfront stem cell transplant (SCT). Thirty and 15 patients eventually underwent autologous and allogeneic SCT after salvage chemotherapy, respectively. The median PFS1 and OS1 in patients with ALK+ALCL and ALK-ALCL were 8.4 and 28.5 months, and 13.1 and 47.7 months, respectively. In patients with ALK+ALCL, the median PFS1, PFS2 and PFS3 were 53.6, 5.2 and 2.3 months, respectively. The median OS1, OS2 and OS3 were not reached, 47.3 and 6.1 months, respectively. In patients with ALK-ALCL, the median PFS1, PFS2 and PFS3 were 12.9, 3.0 and 2.0 months, respectively. The median OS1, OS2 and OS3 were 54.3, 10.8 and 5.8 months, respectively. Interestingly, there were no significant difference in PFS2 between ALK+ALCL and ALK-ALCL. However, OS2 was significantly longer in patients with ALK+ALCL, suggesting possibly continued chemosensitivity of recurrent ALK+ALCL. A total of 30 patients received BV in 1st salvage (15 patients) and after 2nd salvage (15 patients).The use of BV at 1st salvage was associated with significantly longer PFS2 and OS2 both in patients with ALK-ALCL but not with ALK+ALCL likely due to small number of cases. Mutivariate analysis adjusting baseline PIT risk factors and the duration of the response to first line therapy revealed that use of BV (at any point in the salvage setting) is significantly associated with longer OS2 (HR: 0.43, 95%CI: 0.23-0.80). Overall, 12 patients experienced relapse/progression after BV treatment. The median OS after BV failure was 1.4 months (95%CI: 0.5-9.5 months) (Figure). Summary: Survival outcome for relapsed/refractory patients with ALK+ and ALK- patients is improved with BV. However, survival outcome after BV failure is very poor. A new treatment strategies to consolidate or maintain the response after BV and to develop more safe and better therapeutic options are needed. Figure 1. Figure 1. Disclosures Fanale: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Westin:Spectrum: Research Funding. Nastoupil:Celgene: Honoraria; Genentech: Honoraria; AbbVie: Research Funding; Janssen: Research Funding; TG Therapeutics: Research Funding. Wang:Celgene: Research Funding.

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