Practice Patterns of Re-Initiation of Therapy at Time of Relapse or Progression Post- Autologous Stem Cell Transplant (ASCT) Among Patients with AL Amyloidosis

Abstract Background: Among patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur (Milani and Dispenzieri, International Society of Amyloidosis 2016). AL amyloidosis patients who are treated with high dose chemotherapy followed by autologous stem cell transplant (ASCT) are a relatively low-risk and homogenous population, making them an ideal group to study practice patterns. Methods: We conducted a retrospective study to evaluate the patterns of relapse or progression and the timing of re-initiation of therapy among 146 patients who were initially treated with ASCT at Mayo Clinic between 1996 and 2009 and who received second-line therapy between 7/9/1997 and 4/12/2012. Results: The median time from ASCT to second-line therapy was 23.6 months and the median follow up post ASCT was 57.5 months. The indications for second-line treatment were: 1) both hematologic and organ progression 24.7% (36 patients); 2) organ progression only 41.1% (60); 3) hematologic relapse only 34.2% (50). The median dFLC at the time of starting second-line therapy was 10.5 mg/dL (1.6 - 59.5 mg/dL), which was 44.9% (13.8-167.2%) of dFLC level at diagnosis. Increase in proteinuria by > 50% from nadir (that was also at least 1g/24 hours, i.e. renal progression) was present in 35.8%. Increase in NT proBNP by >30% from nadir and minimum of 300 pg/mL was present in 48.9% of patients. The respective 4 years overall survival rates from the time of ASCT were 87.8%, 63.9%, and 56.7% (p=0.0016) for patients who had hematologic relapse, organ progression only and both organ and hematologic progression. Comparisons of laboratory markers at diagnosis, nadir of post ASCT and initiation of second-line therapy are listed in the table. Conclusions: Our study investigated the patterns of relapse / progression following upfront ASCT. This provides some insights on practice patterns of when physicians re-initiate therapy. Table Table. Disclosures Gertz: NCI Frederick: Honoraria; Celgene: Honoraria; Med Learning Group: Honoraria, Speakers Bureau; Research to Practice: Honoraria, Speakers Bureau; Novartis: Research Funding; Prothena Therapeutics: Research Funding; GSK: Honoraria; Sandoz Inc: Honoraria; Ionis: Research Funding; Alnylam Pharmaceuticals: Research Funding; Annexon Biosciences: Research Funding. Kumar:Millennium: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; AbbVie: Research Funding; Glycomimetics: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Research Funding; Kesios: Consultancy. Kapoor:Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Dispenzieri:Prothena: Membership on an entity's Board of Directors or advisory committees; Alnylam: Research Funding; Celgene: Research Funding; Jannsen: Research Funding; pfizer: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Genes Influencing the Development and Severity of Chronic ITP Identified through Whole Exome Sequencing

Blood ◽

10.1182/blood.v126.23.73.73 ◽

2015 ◽

Vol 126 (23) ◽

pp. 73-73 ◽

Cited By ~ 3

Author(s):

Jenny M. Despotovic ◽

Linda M. Polfus ◽

Jonathan M. Flanagan ◽

Carolyn M. Bennett ◽

Michele P Lambert ◽

...

Keyword(s):

T Cell ◽

Board Of Directors ◽

Research Funding ◽

Second Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Chronic Itp ◽

Line Therapy ◽

Whole Exome ◽

Phenotype Data

Abstract Background: Chronic immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by antibody mediated platelet destruction and impaired production. Sustained autoimmunity in chronic ITP appears to be due to generalized immune dysregulation including altered T cell balance with a shift toward immune activation (increased Th1/Th2 ratio) as well as decreased number and impaired function of regulatory T cells (Treg). The cause of these abnormalities has not been fully elucidated and is likely multifactorial, but genetic factors may be involved in ITP pathogenesis. Improved understanding of genetic influences could lead to novel therapeutic approaches. Aim: To identify genetic variants that may be involved in chronic ITP susceptibility and severity. Methods: Whole exome sequencing (WES) was performed on 262 samples with robust phenotype data on children with chronic ITP from the North American Chronic ITP Registry (NACIR, n= 173) and the Platelet Disorders Center at the Weill-Cornell Medical Center (n=89). All but three patients were ≤19 years old at diagnosis; 83% had primary ITP, 10% had Evans syndrome, 7% had other autoimmune disorders. Sequencing data for ITP cases of European American (EA) ancestry were compared to EA controls with platelets >150 x 109/L sequenced in the Atherosclerosis Risk in Communities (ARIC) Study (N=5664) to identify candidate genes associated with ITP susceptibility. Analyses filtered variants on a minor allele frequency (MAF) <0.01 as well as functionality of nonsynonymous, stop gain, splicing, stop loss, and indel variants. Both Fisher-Exact tests of single variants and Firth logistic regression for gene-based tests, accounting for an unequal proportion of cases compared to controls, were used. A Bonferroni corrected threshold based on 16,532 genes was calculated at 3.0x10-6. In a separate analysis, phenotype data for ITP cases were reviewed and cases stratified by disease severity according to second line treatment needed (Yes =139, No=113) and compared to ARIC EA controls with platelet count >150 x 109/L (N=5664). Results: Several damaging variants identified in genes involved in cellular immunity had a significantly increased frequency in the EA ITP cohort (Table). The most significant associations were detected in the IFNA17 gene, which is involved in TGF-β secretion and could affect number and function of the Treg compartment. IFNA17 rs9298814 (9:21227622 A>C) was identified in 26% of cases in the EA ITP cohort compared to <0.01% of EA controls, and other low frequency but presumed deleterious variants were also identified in IFNA17. IFNA17 gene variants remained significant in the most severely affected patients, specifically those requiring second line therapy, providing further evidence for this gene's functional relevance in the pathogenesis and pathophysiology of ITP. Other genes with known impact on T cell number or function, including DGCR14, SMAD2 and CD83 also contained variants with increased frequency in the EA ITP cohort. IFNLR1 and REL genes were also significantly associated with need for second line ITP therapy. Analysis of this large cohort did not validate any of over 20 variants that have been previously published as candidates for ITP susceptibility or evolution to chronic ITP. Conclusion: Damaging variants in genes associated with cellular immunity have an increased frequency in children with chronic ITP compared to controls, providing further evidence for the role of T cell abnormalities in the pathophysiology of ITP. The IFNA17 and IFNLR1 genes maintained significance when the ITP cohort was stratified according to disease severity, and may be important candidate genes involved in immune regulation and sustained autoimmunity associated with chronic ITP. Table. Genes identified through WES analysis of children with chronic ITP. Gene Function Relevant to ITP Pathophysiology Minor Allele Count (MAC)Cases Controls p value EA Chronic ITP vs. EA ARIC (non-ITP) controls N=172 N=5664 IFNA17 Treg, TGF-β signaling 91 17 3.97x10-13 DGCR14 IL-17 induction 14 3 1.27x10-10 SMAD2 TGF-β signaling 1 0 5.62x10-22 CD83 Th17/Treg balance 2 3 1.67x10-6 EA Chronic ITP requiring Second Line Therapy vs. EA ARIC (non-ITP) controls N=139 N=5664 IFNLR1 Class II cytokine receptor 2 1 3.95x10-15 IFNA17 Treg, TGF-β signaling 75 17 3.40x10-7 REL T and B cell function, inflammation 2 0 1.39x10-14 Disclosures Off Label Use: Off-label use of CliniMACS purified CD34+ cells. Lambert:GSK: Consultancy; NovoNordisk: Honoraria; Hardin Kundla McKeon & Poletto: Consultancy. Recht:Baxalta: Research Funding; Kedrion: Consultancy. Bussel:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; protalex: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; rigel: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Optimal Therapy for Relapsed AL Amyloidosis Post Autologous Stem Cell Transplant

Blood ◽

10.1182/blood-2019-125453 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3171-3171

Author(s):

M Hasib Sidiqi ◽

Abdullah S. S. Al Saleh ◽

Iuliana Vaxman ◽

Angela Dispenzieri ◽

Francis K. Buadi ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Al Amyloidosis ◽

Cell Transplant ◽

Advisory Committees ◽

Free Survival ◽

Treatment Regimens ◽

2Nd Generation

Introduction: There is a paucity of randomized trials to guide therapy for relapsed AL amyloidosis with treatment regimens generally extrapolated from experience in multiple myeloma. Methods: We conducted a retrospective review of patients who relapsed after receiving autologous stem cell transplant at Mayo Clinic. Patients treated for first relapse between January 2004 and December 2018 were included. Results: Three hundred and twenty-one patients were seen for relapsed AL amyloidosis post ASCT during the study period. Baseline characteristics were typical for a cohort with AL amyloidosis and are listed in Table1. 39% received therapy prior to transplant, conditioning in the majority (75%) was melphalan 200mg/m2. The median progression free survival from transplant (PFS1) was 30.7 months. Of the 321 patients 294 received treatment for relapsed disease. We categorized treatment regimens according to commonly used combinations and drug classes to further analyze outcomes. 34 patients were excluded from this analysis as they either proceeded directly to second ASCT (n=10) or received an atypical regimen not commonly considered for AL amyloidosis (n=24). Five categories of therapy regimens were identified, thalidomide based (n=110), melphalan plus steroids (n=31), 2nd generation immunomodulatory (IMiD) drug +/- alkylator (n=76), proteasome inhibitor (PI) +/- alkylator (n=116), PI plus IMiD (n=16), or daratumumab based (n=9). Disease and treatment characteristics for patients treated with these regimens are listed in Table 2. Patients treated with thalidomide had the shortest PFS1 (17.7 months) but PFS1 was similar for those treated with melphalan plus steroids, PI+IMiD and 2nd generation IMiDs (25.5, 24.3 and 25.6 months respectively). Patients treated with a PI +/- alkylator and daratumumab based regimen had the longest PFS1 (36.7 and 41.9 months respectively). The median duration of therapy was longer in patients treated with a 2nd generation IMiD or daratumumab based regimen (10.2, 12, 6.1, 5.5, 6.2 and 5.9 months for Dara based, 2nd generation IMiD, PI+/- alkylator, PI+IMiD, melphalan plus steroids and thalidomide based respectively). Hematologic response rate was lowest in those treated with melphalan plus steroids or thalidomide based regimens (44% and 55% respectively) and highest for patients treated with a PI+/- alkylator, (Figure 1). Progression free survival from relapsed therapy (PFS2) was longest amongst patients treated with daratumumab based regimens, PI +/- alkylator and 2nd generation IMiDs (not reached, 29.9 and 26.7 months respectively), Figure 2A. Overall survival from time of relapsed therapy favored patients treated with daratumumab based regimens, 2nd generation IMiDs and PI +/- alkylator, Figure 2b). Conclusion: A second generation IMiD based regimen or PI +/- alkylator produce high response rates and prolonged progression free and overall survival for relapsed AL amyloidosis. Patients treated with daratumumab based regimens and those treated with a PI plus IMiD also appear to do well, although numbers were low in our study. Patients treated with melphalan plus steroids or thalidomide based combinations have inferior outcomes and these regimens should be avoided. Disclosures Dispenzieri: Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:Karyopharm: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Janssen: Consultancy; alexion: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kapoor:Glaxo Smith Kline: Research Funding; Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Janssen: Research Funding. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Appellis: Consultancy; Amgen: Consultancy; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; Annexon: Consultancy. OffLabel Disclosure: Daratumumab off label use for AL amyloidosis.

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Improved Progression-Free Survival (PFS) of Alemtuzumab (Campath®, MabCampath®) Plus Fludarabine (Fludara®) Versus Fludarabine Alone as Second-Line Treatment of Patients with B-Cell Chronic Lymphocytic Leukemia: Preliminary Results From a Phase III Randomized Trial.

Blood ◽

10.1182/blood.v114.22.537.537 ◽

2009 ◽

Vol 114 (22) ◽

pp. 537-537 ◽

Cited By ~ 2

Author(s):

Andreas Engert ◽

Liana Gercheva ◽

Tadeusz Robak ◽

Pilipenko Galina ◽

Jingyang Wu ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

Second Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Free Survival ◽

Line Therapy

Abstract Abstract 537 Introduction: Single-arm pilot and Phase II trial data suggested that the combination of fludarabine and alemtuzumab (FluCam) may improve outcome for patients (pts) with relapsed or refractory chronic lymphocytic leukemia (CLL). To validate these observations, a Phase III, multicenter, open-label, randomized study was conducted to compare the efficacy and safety of FluCam vs. fludarabine (Flu) alone as second-line therapy for pts with relapsed or refractory CLL. Methods: Patients with Rai Stages I-IV were randomized to FluCam or Flu using the minimization method to ensure a balance between treatment arms by study center, Rai stage, disease status, age, sex, prior Flu therapy, and maximum lymph node (LN) size. FluCam was administered in Phases A and B. Patients received escalating doses of intravenous (IV) alemtuzumab alone (Phase A). Once alemtuzumab 30 mg IV was tolerated, pts received FluCam as Flu 30 mg/m2 IV followed immediately by alemtuzumab 30 mg IV on days 1-3 of a 28 day cycle (Phase B). In the Flu arm, pts received 25 mg/m2IV on days 1-5 of a 28 day cycle. For both arms, all pts could receive up to six cycles depending on response and toxicity. All pts received prophylaxis with trimethoprim/sulfamethoxazole DS and famciclovir until CD4+ counts were ≥200 cells/μL. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response (OR), complete response (CR), overall and 3 year survival, and safety. The primary analysis was based on the independent response review panel's (IRRP) assessment of response and date of progression for each patient. Two interim analyses were prospectively planned and conducted by the data and safety monitoring board (DSMB) with the final analysis planned after a total of 190 events. The 2nd interim analysis included 139 PFS events and met the pre-specified criteria; the DSMB recommended early study termination. Results: 335 pts were randomized (FluCam n=168 and Flu n=167); Rai Stage III-IV: 37%; median age: 60 years; prior Flu therapy: 20% and maximum LN size ≥5 cm: 14%. The median treatment cycles received were 6 for both arms. 60% of FluCam and 64% of Flu pts received 6 cycles of treatment. The median IRRP determined PFS for FluCam was significantly prolonged compared to Flu (29.6 months vs. 20.7 months, respectively; p=0.005; HR 1.63 [95% CI: 1.16, 2.28]; Figure 1). Median PFS by Rai Stage was: Stage I-II - 27.4 months for FluCam (n = 105) vs. 21.3 months for Flu (n = 103), p=0.215; Stage III-IV - 26.1 months for FluCam (n = 61) vs. 12.1 months for Flu (n = 62), p=0.003. Per investigator response assessment, FluCam resulted in significantly higher OR and CR rates (OR: FluCam 84.8% vs. Flu 67.9%, p<0.001; and CR: FluCam 30.4% vs. Flu 16.4%, p=0.002). The IRRP assessment of response was not completed for all pts and is not availabel for the 2nd interim analysis. No differences in survival have been observed (FluCam 37 deaths and Flu 41 deaths) with a median follow up of 17 months. Adverse events (AEs) occurring in >10% of the pts included pyrexia, neutropenia, leukopenia, thrombocytopenia, anemia, chills, lymphopenia, rash, infusion related reactions, nausea and urticaria in the FluCam arm; and, neutropenia, thrombocytopenia, anemia and leukopenia in the Flu arm. Treatment-emergent grade 3/4 thrombocytopenia (18% vs. 22%), neutropenia (60% vs. 66%) and anemia (13% vs. 22%) were comparable in FluCam vs. Flu arms. Overall, 33% (n=54) of pts in the FluCam arm experienced a SAE vs. 26% (n=42) in the Flu arm. Reported SAEs for neutropenia were 4.9% in the FluCam arm and 1.8% in the Flu arm; however, febrile neutropenia was similarly reported in the two arms 3.7% vs 3.6% of pts, respectively. Infections including CMV occurred in 47% and 35% of the FluCam and Flu pts, respectively. Symptomatic CMV infection occurred only in the FluCam arm in 8% of pts, of which 1% were SAEs and 0% classified as grade 4 or higher. Deaths occurring on therapy or within 30 days after last dose were 2% on the FluCam arm vs. 5% on the Flu arm. Conclusions: The 2ndinterim analysis indicates that the combination of FluCam is superior to Flu as second-line therapy for pts with relapsed or refractory CLL, including those with advanced disease stage. With significantly longer PFS, higher OR and CR rates, an acceptable safety profile and a convenient administration regimen, FluCam may be an additional second-line treatment option for pts with relapsed or refractory CLL. Disclosures: Engert: Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Alemtuzumab (Campath, MabCampath) is indicated for the treatment of CLL. This trial examined the use of alemtuzumab in combination with fludarabine monophospate.. Gercheva:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Robak:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Galina:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wu:Genzyme Corporation: Employment. Sirard:Genzyme Corporation: Employment. Elter:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Second Line Therapy with Second Generation TKI After Intolerance to Imatinib Based Treatments Showed High Overall Survival in Contrast to Second Line Therapy After Resistance; Results of the Randomized CML Study IV

Blood ◽

10.1182/blood.v118.21.781.781 ◽

2011 ◽

Vol 118 (21) ◽

pp. 781-781

Author(s):

Susanne Saussele ◽

Michael Lauseker ◽

Ulrike Proetel ◽

Martin C. Müller ◽

Benjamin Hanfstein ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Second Generation ◽

Chronic Phase ◽

Imatinib Therapy ◽

Second Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Line Therapy

Abstract Abstract 781FN2 Introduction: Data on second line therapy with second generation tyrosine kinase inhibitors (TKI) in CML treatment were generated mainly from phase II/III industry initiated trials (Review Hehlmann Exp Op. 2011). 24-month overall survival (OS) varies between 88% and 94% after intolerance and/or resistance to imatinib for chronic phase (CP) and between 67% and 72% for accelerated phase (AP) or blast crisis (BC). Intention to treat analyses including outcome of patients after discontinuation of first line therapies have not been available as yet. We thought to evaluate overall and progression-free survival (OS and PFS) of imatinib intolerant vs. resistant patients under second line TKI with long-term follow-up within an investigator initiated trial. Methods: We analyzed data of the German CML study IV, a randomized 5-arm trial to optimize imatinib therapy on an intention to treat basis. According to protocol, follow-up of patients on and after second generation TKI after imatinib intolerance and/or resistance was continued for OS and PFS. Analysis of PFS was only relevant, if intolerance and resistance to imatinib therapy occurred while a patient was still in chronic phase (CP). Patients were censored at the time of allogeneic stem cell transplantation (allo-SCT). Results: From July 2002 to December 2010, 1,502 patients with Philadelphia chromosome and /or BCR-ABL positive CML in CP were randomized. 129 patients of the “imatinib after interferon arm” and 36 other patients had to be excluded (14 due to incorrect randomization or withdrawal of consent, 22 with missing baseline information). 1337 were randomized to primary imatinib treatment (imatinib 400 mg vs. imatinib 800 mg vs. imatinib in combination with either interferon alpha or araC). Of these, 234 (17%) discontinued imatinib therapy. 156 patients were treated with 2nd generation TKI, 61 were directly referred to allo-SCT, 17 patients received other regimens (including interferon alpha only or hydroxyurea). 120 of 156 patients started second generation TKI therapy (nilotinib, n=41, dasatinib, n=75, bosutinib, n=2, nilotinib and dasatinib, n=2) within 3 months after stopping imatinib, received treatment for at least one week and were evaluable for PFS and OS. 36 patients received second TKI later (median 10 months, range 3.5–61.4). Median age was 50 years (range 16–78), 42.5% were female. 48 patients were intolerant, 48 failed imatinib within CP and 24 after loss of CP (accelerated phase, n=10, blast crisis, n=14). Median time to second generation TKI was 17 months (range 1.4–97 months) and median follow-up after start of second-line TKI 31 months (range 0.2–71 months). Risk stratification according to the EUTOS Score was high in 20 patients (17%) and low in 94 patients (78%) and unknown in 6 patients (5%). OS for all 120 patients 3 years after start of second generation TKI was 73%, 96% for intolerant and 80% for resistant patients in CP and 19% for resistant patients in advanced disease (s. Fig. 1). According to EUTOS score, 3-year OS was 78% for low and 56% for high risk patients. Probability of PFS of the 96 patients in 1st CP after 3 years was 96% for intolerant and 76% for resistant patients. After 2nd generation TKI, 18 patients received an allo-SCT: all were in CP, 2 patients after imatinib intolerance, 16 patients after imatinib resistance. Conclusion: Survival on second generation TKI is high for imatinib intolerant patients in first CP but much lower for resistant patients in first CP or for patients with advanced disease phases. Alternative treatment strategies are warranted for these patient groups. Disclosures: Krause: Micromet: Research Funding. Kneba:Hoffmann La Roche: Honoraria. Hochhaus:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, 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; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. German CML Study Group:Deutsche Krebshilfe: Research Funding; Novartis: Research Funding; BMBF: Research Funding; EU: Research Funding; Roche: Research Funding; Essex: Research Funding.

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Real-World Outcomes for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide, Bortezomib, and Dexamethasone, or Bortezomib and Dexamethasone: An Enhanced Electronic Health Records Database Analysis

Blood ◽

10.1182/blood-2018-99-111121 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2243-2243

Author(s):

Ajai Chari ◽

Brian Ung ◽

Marc Tian ◽

Amit Agarwal ◽

Kejal Parikh

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Second Line ◽

Second Line Therapy ◽

Employment Equity ◽

Advisory Committees ◽

Line Therapy ◽

Equity Ownership

Abstract Background: For transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), the only category 1 regimens recommended by the National Comprehensive Cancer Network (NCCN) are lenalidomide and dexamethasone (Rd)-based, including triplet therapy with lenalidomide, bortezomib, and dexamethasone (RVd) (NCCN Myeloma v4.2018). Other doublet regimens, such as bortezomib and dexamethasone (Vd), are still a first-line option for patients with NDMM, especially for those who are elderly and/or frail. However, the latter population is either excluded or markedly underrepresented in clinical trials. Using an electronic health records (EHRs) database, we compared outcomes when either RVd or Vd were used in the treatment of transplant-ineligible patients with NDMM in a real-world practice setting, after adjusting for baseline demographic and clinical differences between the two cohorts. Methods: A retrospective observational study of patients with NDMM was conducted using EHRs from a nationally representative database (Flatiron Health). The Flatiron Network database is an enhanced oncology EHR database of patients treated at 265 clinics throughout the USA. Patients diagnosed with multiple myeloma, ICD-9 (203.0x) or ICD-10 (C90.xx), between January 2011 and May 2018 who were treated with RVd or Vd and did not undergo stem cell transplantation were included in the analysis. The primary comparison was time to next therapy (TTNT) in the overall population and in a subset of frail patients, as determined by a composite score based on age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, and Charlson Comorbidity Index (CCI). Data regarding overall and progression-free survival (PFS) were limited as patient data prior to adoption of the Flatiron Network database were incomplete. Treatment-free interval (TFI) for patients who initiated a second-line therapy was defined as time from start of first-line to start of second-line therapy minus the duration of therapy (DOT). The Kaplan-Meier and Cox proportional hazard methods were used to calculate TTNT after adjusting for differences in patient baseline demographic and clinical characteristics. Results: Of the 8,470 transplant-ineligible patients with NDMM in the database, 2,369 were treated with either RVd (n = 1,309) or Vd (n = 1,060) and met the criteria for inclusion in this analysis. Patients treated with Vd were more likely to be older (median age 75 vs 70 years; P < 0.0001), frail (76.3% vs 65.4%; P = 0.0002), have creatinine clearance < 30 mL/min (23.9% vs 10.7%, P < 0.0001), have a higher ECOG PS score (P = 0.0031), and have International Staging System stage III disease (45.1% vs 28.8%; P < 0.0001). There were no significant differences in baseline neutropenia, anemia, or thrombocytopenia, or in median CCI. The proportion of patients with high-risk cytogenetics was lower in the Vd group (19.7% vs 26.0%; P < 0.0001). The mean DOT was longer for RVd (11.4 ± standard deviation [SD] 13.3 months) than for Vd (7.7 ± SD 9.7 months). However, the median adjusted TTNT was significantly longer with RVd than Vd (40.9 vs 14.8 months; hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.33-0.55; P < 0.0001). The proportion of patients initiating a new treatment was lower in the RVd group (24.8% vs 40.6%; P < 0.0001). Among those who initiated a second-line therapy, the mean TFI for RVd compared with Vd was 42.6 versus 39.3 days, respectively (P = 0.2214). Among the 735 frail patients (416 RVd and 319 Vd), the median TTNT was significantly longer with RVd (32.6 vs 17.1 months; HR 0.40; 95% CI 0.29-0.54; P < 0.0001; Figure). Similar to the overall population, there were no significant differences in TFI (54.9 vs 29.6 days, P = 0.2598) and a significantly higher proportion of Vd patients initiated a new treatment (22.1% vs 36.4%; P < 0.001). Conclusions: In this real-world practice setting where PFS cannot be measured directly, triplet therapy with RVd significantly prolonged TTNT compared with Vd by 26.1 months in the overall patient population, and by 15.5 months in frail transplant-ineligible patients with NDMM. Disclosures Chari: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Array Biopharma: Research Funding; Bristol Myers Squibb: Consultancy. Ung:Celgene Corporation: Employment, Equity Ownership. Tian:Celgene Corporation: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Parikh:Celgene Corporation: Employment, Equity Ownership.

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Updated 6 Year Follow-Up Of The PRIMA Study Confirms The Benefit Of 2-Year Rituximab Maintenance In Follicular Lymphoma Patients Responding To Frontline Immunochemotherapy

Blood ◽

10.1182/blood.v122.21.509.509 ◽

2013 ◽

Vol 122 (21) ◽

pp. 509-509 ◽

Cited By ~ 56

Author(s):

Gilles Andre Salles ◽

John Francis Seymour ◽

Pierre Feugier ◽

Fritz Offner ◽

Armando Lopez-Guillermo ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Second Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Free Survival ◽

Rituximab Maintenance ◽

Line Therapy

Abstract The intergroup PRIMA Phase III study was designed to investigate the potential benefit of 2-years of rituximab maintenance in patients with follicular lymphoma (FL) responding to one of three non-randomised first line immunochemotherapy treatments. The results of the final analysis with 36 months follow-up (Salles et al., Lancet 2011) demonstrated a significant reduction of the risk of progression or death with a hazard ratio (HR) of 0.55 in favour of patients randomized to rituximab maintenance. We present here the updated results with 3 additional years of follow-up. From December 2004 until April 2007, 1217 patients were enrolled from 223 centres and complete data were available for 1193 patients who had the following pre-induction treatment characteristics: median age 56 years [range 22–87]; 52% male; 90% Ann Arbor stage III-IV; 33% B symptoms; 56% bone marrow involvement; 4% ECOG performance status >1; 34% elevated LDH; 32% β2-microglobulin >3mg/L; FLIPI score 0-1 (21%), FLIPI 2 (36%), FLIPI 3-5 (43%). Most patients (75%) received R-CHOP induction (22% R-CVP, 3% R-FCM). Patients responding to induction therapy were stratified based on their immunochemotherapy regimen and response [CR/CRu versus PR] and randomized to observation or rituximab maintenance, 1 infusion (375 mg/m2) every 8 weeks for 2 years. A total of 1018 randomised patients were analyzed according to the ITT principle (513 observation / 505 rituximab maintenance). All initial pre-treatment characteristics were well balanced between arms and the response status at time of randomization was CR=39%; CRu=32% and PR=28% (others 1%). With a median follow-up of 73 months from randomization, 6-year progression free survival estimate was 42.7% (95% CI 38 – 46.9%) in the observation arm (284 events, median=48 months) and 59.2% (95% CI 54.7 – 63.7%) in the rituximab maintenance arm (194 events, median not reached), respectively (stratified Log-Rank, P<. 0001; HR = 0.58 ; 95% CI 0.48 - 0.69). In pre-planned analyses of patients subgroups categorized by age, sex, FLIPI score category, induction chemotherapy and response to induction, the effect of rituximab maintenance was examined and found to be consistent among these different subgroups. In a Cox regression multivariate analysis, rituximab maintenance (HR=0.57; P<.0001) as well as older age (HR=0.79; P=.015), female sex (HR=0.72; P=.0003) and low or intermediate FLIPI groups (HR=0.67; P<.0001) were all significant variables associated with superior progression free survival. A significant reduction in the risk of starting a new anti-lymphoma treatment (HR=0.63, 95% CI 0.52 - 0.76) or starting a new chemotherapy (HR=0.70, 95% CI 0.57 - 0.86) were also observed for rituximab maintenance. The rate of histological transformation did not appear to differ between the 2 treatment arms: in the observation arm, transformation was documented in 24 patients (114 cases with morphological documentation out of 278 progressions) versus 16 patients in the rituximab maintenance arm (80 out of 186) respectively. Overall response rate to second-line therapy was reported by investigators to be 180/227 (79%) in patients from the observation arm (CR/CRu=61%; PR=19%) versus 109/144 (76%) in patients from the rituximab maintenance arm (CR/CRu =51%; PR=22%) (P=NS). At the time of the data cut-off, overall survival (OS) remains favourable in both study arms: 58 patients (11.3%) have died in the observation arm (6-years OS estimate 88.7%) compared to 59 patients (11.7%) in the rituximab maintenance arm (6-year OS estimate 87,4%). Main causes documented for death in the observation and rituximab maintenance arm respectively were lymphoma (28 ; 28), other malignancy (19 ; 5) and infections (4 ; 7). No new significant safety data were captured with this additional follow-up period. In conclusion, with 3 additional years of follow-up, these data demonstrate a sustained and persistent benefit of 2 years of rituximab maintenance therapy after immunochemotherapy, resulting in improved progression free survival. No additional or unexpected long term toxicities were observed and second line therapy efficacy results did not significantly differ between the 2 study arms. Overall survival appears very favourable for these randomized patients. Disclosures: Salles: Roche: Consultancy, Honoraria, Research Funding. Seymour:Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau, Travel support Other; Genetech: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Feugier:Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Offner:Lilly: Membership on an entity’s Board of Directors or advisory committees. Lopez-Guillermo:Roche: Membership on an entity’s Board of Directors or advisory committees. Belada:Roche: Consultancy. Catalano:Roche: Membership on an entity’s Board of Directors or advisory committees. Haioun:Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Simpson:Janssen Research & Development: Honoraria. Leppa:Roche: Consultancy, Honoraria, Research Funding, Travel support Other. Soubeyran:Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Hagenbeek:Takeda/Millennium: Consultancy. Casasnovas:ROCHE: Consultancy, Honoraria, Research Funding. Coiffier:Millennium Pharmaceuticals : Consultancy. Tilly:Roche: Honoraria; Celgene: Honoraria, 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; Pfizer: Honoraria; Janssen: Honoraria; Amgen: Research Funding.

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Delineation of the timing of second-line therapy post–autologous stem cell transplant in patients with AL amyloidosis

Blood ◽

10.1182/blood-2017-05-783415 ◽

2017 ◽

Vol 130 (13) ◽

pp. 1578-1584 ◽

Cited By ~ 9

Author(s):

Yi L. Hwa ◽

Rahma Warsame ◽

Morie A. Gertz ◽

Francis K. Buadi ◽

Martha Q. Lacy ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Al Amyloidosis ◽

Cell Transplant ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Key Points

Key Points Organ progression at second-line therapy predicated inferior survival. Patients relapsing from >VGPR had a longer time to develop organ progression.

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Impact of Therapy Choice on Fatigue in Adults with Immune Thrombocytopenia

Blood ◽

10.1182/blood-2020-139746 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 19-20

Author(s):

Jennifer Diraimo ◽

Caroline Kruse ◽

Michele P. Lambert ◽

Alexandra Kruse

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Treatment History ◽

First Line Therapy ◽

Line Therapy

Background:Immune thrombocytopenia purpura (ITP) is an autoimmune bleeding disorder that is heterogeneous in presentation, disease course, treatment response, and impact on quality of life. Treatments often cause unpleasant side effects, and prolonged use can lead to tolerability issues and toxicity. Both disease symptoms and treatments available impact the health-related quality of life (HRQoL) among patients living with this rare condition. Here, we compare self-reported fatigue and its impact among adult ITP patients and determine whether these fatigue levels differ depending on treatment status. Methods: For this study, we used three of the five surveys from the PDSA Natural History Study Registry including; treatment history and two adult QoL surveys. As of June 2020, 357 adult patients completed the survey assessing treatment history. A total of 310 adult patients completed the adult QoL (part one) survey, and 301 adults completed the adult QoL (part two) survey. Patients were stratified by 1) no treatment received 2) treated in the past 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Results: Among the 357 completed surveys on treatment history, 11% (n=40) reported they have never received treatment for their ITP, while 46% (n=166) have in the past, and 43% (n=158) currently receive therapy (within the last six months). Among those currently on treatment, 82% receive monotherapy; 47 (26%) use a first-line therapy (corticosteroid, IVIG, or Anti-D), and 78 (43%) are using a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported include TPO-RA's (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%), other second-line treatments (such as MMF, dapsone etc.), and "other" therapies including complementary treatments (14%). Overall, 93 (23%) reported having had a splenectomy at some point to manage their active ITP. When asked to reflect on general tiredness, 98% of patients (n=310) reported being tired overall, with 55% reporting feeling tired 'almost always/often' regardless of treatment group or type. Those who have never been treated reported they felt tired 94% of the time, and 55% reported feeling tired 'almost always/often'. Among those who are not currently on treatment (but have received therapy in past), 99% reported feeling tired overall, and 50% reported feeling tired 'almost always/often'. Respondents using a first line therapy reported feeling tired overall 100% of the time, and reported feeling tired 53% 'almost always/often'. Respondents using a second line therapy reported feeling tired 99% of the time, and indicated they were tired 59% 'almost always/often'. There were no significant differences between these treatment types and groups identified. When asked to reflect on fatigue levels over the last seven days, collectively, 86% reported fatigue, and 30% reported experiencing it 'very much/quite a bit'. Among those who had never been treated, 85% reported fatigue, and indicated they felt fatigue 27% of the time 'very much/quite a bit'. Respondents who were not receiving treatment reported feeling fatigue 84% of the time, of which 26% was experienced 'very much/quite a bit'. Among those receiving a first line therapy, 90% reported fatigue in the last seven days, and 34% reported they experienced this 'very much/quite a bit'. Those using a second line therapy reported feeling fatigue 91% of the time, and 29% reported this was 'very much/quite a bit'. There were no significant difference among these treatment types and groups. Conclusion: Reported fatigue and overall tiredness are high among those currently on treatment, not on treatment, and those who have never been treated for their ITP. We did not find that fatigue levels were related to treatment type or group, indicating that the underlying causes may not be platelet count, or disease severity, but rather a combination of factors associated with having an unpredictable chronic disease. The multi-faceted effects of ITP often take a significant toll on patients' quality of life. The registry continues to collect data with the intent of understanding the longitudinal impact of ITP and in future with more of a sample size we can learn if these trends continue. Disclosures Kruse: CSL Behring: Other: Grant paid to PDSA; UCB: Other: Grant and consultancy fee, all paid to PDSA; Rigel: Other: Grant paid to PDSA; Principia: Other: Grant paid to PDSA; Pfizer: Other: Grant and consultancy fee, all paid to PDSA; Argenx: Other: Grant paid to PDSA; Amgen: Other: Grant and honorarium, all paid to PDSA; Novartis: Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work. Lambert:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Octapharma: Consultancy, Research Funding; Bayer: Consultancy; Argenix: Consultancy; ClinGen: Honoraria; Platelet Disorder Support Association (PDSA): Consultancy; 22qSociety: Consultancy; ITP Australia: Consultancy; CdLS Foundation: Consultancy; RDMD ITP study: Consultancy; Sysmex: Research Funding; AstraZeneca: Research Funding.

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Treatment Patterns and Outcomes Following Initial Relapse in Patients with Relapsed Systemic Immunoglobulin Light Chain Amyloidosis

Blood ◽

10.1182/blood.v128.22.3338.3338 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3338-3338

Author(s):

Nidhi Tandon ◽

Surbhi Sidana ◽

Morie A. Gertz ◽

Angela Dispenzieri ◽

Martha Q. Lacy ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Al Amyloidosis ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy

Abstract Introduction Immunoglobulin light chain amyloidosis (AL Amyloidosis) is a plasma cell disorder characterized by deposition of misfolded insoluble protein fibrils (composed of monoclonal κ or λ light chains) in tissues causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT), when eligible, are standard treatment options but relapses remain inevitable for most patients. However, there is a paucity of literature describing relapsed or refractory patients. We performed a retrospective study to analyze the outcomes upon relapse and the impact of type of therapy and retreatment with the same therapy at relapse. Methods Clinical and laboratory data of 1327 consecutive patients with systemic AL amyloidosis seen at Mayo Clinic within 90 days of their diagnosis, between 2006 and 2015, was collected by chart review and analyzed retrospectively. Of these patients, 219 (16.5%) were lost to follow-up. Among the remaining 1108 patients, 366 patients experienced a documented hematological or organ relapse or progression requiring change of first line or start of second line therapy and form the current study population. Overall survival (OS) was calculated from start of second line treatment or progression mandating therapy until death from any cause or the date of last follow up. The OS was estimated using the Kaplan-Meier method and log rank test was used to estimate the difference in survival curves. Results The median age was 62.8 years (36.1 - 85.3); 63.1% were males; 64.7% / 59.3% / 11.4% had cardiac / renal / hepatic involvement and 24.2% / 32.1% / 23.3% / 20.3% had MS I/II/III/IV. The median estimated follow up for this cohort was 69.4 months (95% CI; 64.4, 76.8) from the start of first line therapy and 45.2 months (95% CI; 36.5, 50.6) from the start of second line therapy or progression requiring treatment. The median time to second line treatment or relapse /progression mandating therapy was 16.2 months (1-93) from the start of first line therapy. At relapse, 14 patients underwent ASCT, 165 were treated with proteasome inhibitor (PI) based therapy, 83 with immunomodulator (IMiD) based therapy, 33 with alkylator based therapy, 15 with a combination of PI and IMiD, 10 with steroids, 8 with other therapies and 38 did not receive treatment. Among the 366 patients, 124 (33.9%) required change or reinstitution of therapy during follow up at the time of analysis. The median time to third line treatment or relapse /progression mandating therapy was 31 months (95% CI; 24, 40.5) from the start of second line treatment. The median overall survival (OS) was 76.4 months (95% CI; 65.2, 83.6) from the start of first line therapy and 38.8 months (95% CI; 29.6, 52.6) from the start of second line therapy. The type of therapy at relapse (ASCT vs PI vs IMiD vs melphalan vs steroids and others) did not alter the time to next therapy (ASCT, 43.1m; PI, 31m; IMiD, 37m; melphalan, 20.8m; steroids and others, 20m; p=0.3) and OS (ASCT, 66.9m; PI, 51.1m; IMiD, 51.3m; melphalan, 37.2m; steroids and others, 80.7m; p=0.9) from the start of the second line treatment; as depicted in Figure 1. Retreatment with a different drug class (as the first line treatment) at relapse significantly reduced the time to next treatment (32.3m vs 22 m; p= 0.01) as compared to same therapy; but did not have any impact on survival (30.8m vs 51.1m; p = 0.5); as presented in Figure 2. Conclusion This study provides novel information about outcomes of patients with systemic AL amyloidosis who relapse or progress after first line therapy which could be useful in planning salvage therapies and designing clinical trials. Retreatment with a different therapy at relapse improves time to next therapy but does not impact OS. Hence, we conclude that the patients can fare well post relapse/ progression and can benefit from various treatment regimens including retreatment with the same agent. Disclosures Dispenzieri: Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; Jannsen: Research Funding; pfizer: Research Funding; Alnylam: Research Funding; Celgene: Research Funding. Kapoor:Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Kumar:BMS: Consultancy; Kesios: Consultancy; Glycomimetics: Consultancy; Onyx: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; AbbVie: Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding.

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Anxiety in Adult Patients Living with ITP Stratified across Different Treatment Types and Groups

Blood ◽

10.1182/blood-2020-139681 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-18

Author(s):

Jennifer Diraimo ◽

Caroline Kruse ◽

Michele P. Lambert ◽

Alexandra Kruse

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Treatment History ◽

Line Therapy

Background:Immune thrombocytopenia purpura (ITP) is an autoimmune bleeding disorder that is heterogeneous in presentation, disease course, treatment response, and impact on quality of life. Treatments often cause unpleasant side effects, and prolonged use can lead to tolerability issues and toxicity. Disease symptoms and treatments available impact the health-related quality of life (HRQoL) among patients living with ITP. Here, we compare anxiety and its impact among adult ITP patients and determine whether anxiety levels differ dependent on treatment. Methods: For this study, we used three of the five surveys from the PDSA Natural History Study Registry including; treatment history and two adult QoL surveys. As of June 2020, 357 adult patients completed the survey assessing treatment history. A total of 310 adult patients completed the adult QoL (part one) survey, and 301 adults completed the adult QoL (part two) survey. Patients were stratified by 1) no treatment received 2) treated in the past 3) on therapy within the last six months; patients currently on therapy were further stratified by first and second-line therapy. Results: Among the 357 completed surveys on treatment history, 11% (n=40) have never received treatment for ITP, 46% (n=166) have in past, and 43% (n=158) currently receive therapy (within the last six months). Among those currently on treatment, 82% receive monotherapy; 26% use a first-line therapy (corticosteroid, IVIG, or Anti-D), and 43% are using a second-line therapy (TPO-RA, rituximab, and other second-line options). Therapies reported include TPO-RA's (41%), corticosteroids (24%), IVIG (7%), rituximab (3%), SYK inhibitor (1%), antibiotics (4%), anti-D (1%) and other second-line treatments (such as MMF), and "other" treatments including complementary therapies (14%). Overall, 23% had a splenectomy at some point to manage their active ITP. When asked to reflect on the last seven days, patients completing the QoL survey (n=310), 66% felt anxious; 17% reported this was experienced 'almost always/often'. Among those who have never been treated, feeling anxious was reported 67% of the time; 18% reported feeling this way 'almost always/often'. A similar trend was observed in patients not currently on treatment. Among those receiving a first line therapy, anxiousness was reported 74% overall; 19% 'almost always/often'. Among those receiving a second line therapy, 72% reported feeling anxious; 9% reported feeling this way 'almost always/often'. Differences in high levels of anxiousness reported among the different treatment groups was not significant (X2= 3.4, p=.48). Difficulties focusing were reported (51%, 9% reporting this occurred 'almost always/often'). Among those who have never been treated, difficulties were reported (48%, 12%, 'almost always/often'). Those not currently receiving treatment had difficulties focusing due to anxiety (50%, 4% reporting this 'almost always/often'). Those on first line treatment indicated focus was impacted by anxiety overall (60%, 36% 'almost always/often') and those receiving second-line therapy reported (58%, 8% 'almost always/often'). Differences in high levels of anxiety affecting concentration reported among the treatment groups was significant (X2= 20.87, p=.00033), revealing a higher anxiety profile among those using corticosteroids. When difficulty with focus due to anxiety was compared between those receiving corticosteroids and those receiving a TPO-RA specifically, anxiety was significantly higher in the steroid group (X2=9.15, P=.0024); this trend was not found to be statistically significant among other second line therapies. Conclusion: The physical symptoms of ITP often guide treatment selection for patients however, providers should also focus on mitigating stress and other indicators of mental health in order to provide the best outcome and quality of life in disease course. Differences in interpretation behind the terms feeling 'anxious' vs ' anxiety affecting focus' may explain our conflicting results. Higher anxiety levels (in contrast to higher anxiousness) appeared related to treatment type in those currently receiving therapy; corticosteroid users were more impacted by their anxiety than those receiving TPO-RAs; steroids are known to interfere with mood and concentration, and this is confirmed by patients in this survey. Disclosures Kruse: CSL Behring: Other: Grant paid to PDSA; UCB: Other: Grant and consultancy fee, all paid to PDSA; Rigel: Other: Grant paid to PDSA; Principia: Other: Grant paid to PDSA; Pfizer: Other: Grant and consultancy fee, all paid to PDSA; Argenx: Other: Grant paid to PDSA; Amgen: Other: Grant and honorarium, all paid to PDSA; Novartis: Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work. Lambert:AstraZeneca: Research Funding; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shionogi: Consultancy; Sysmex: Research Funding; RDMD ITP study: Consultancy; ITP Australia: Consultancy; CdLS Foundation: Consultancy; 22qSociety: Consultancy; Platelet Disorder Support Association (PDSA): Consultancy; ClinGen: Honoraria; Bayer: Consultancy; Argenix: Consultancy; Octapharma: Consultancy, Research Funding; Educational Concepts in Medicine: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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