Ibrutinib for Relapsed Mantle Cell Lymphoma after Standard First Line Therapy and ASCT Is Efficacious but Does Not Overcome the Impact of POD24 - a Retrospective Study from the LWP-EBMT

Introduction Standard first line treatment for mantle cell lymphoma (MCL) in fit patients is induction with cytarabine containing chemo-immunotherapy and a consolidative autologous stem cell transplant (ASCT). Responses are excellent but there is a continuous pattern of relapse. Progression within 24 months (POD24) of standard first line therapy including ASCT has been shown to predict poorer outcomes, which may be ameliorated by alloSCT. Ibrutinib, a Bruton's Tyrosine Kinase inhibitor, is an effective therapy for relapsed MCL. However, there is a paucity of published data of ibrutinib's efficacy in patients treated at relapse after standard first line treatment with ASCT and very little regarding the impact of POD24 on outcomes after ibrutinib and outcomes of subsequent alloSCT. Methods This was a retrospective analysis of the EBMT registry. The inclusion criteria were: patients with MCL ≥18 years old, 1st line therapy containing cytarabine and rituximab, ASCT in first CR/PR between 2009 and 2016 and received ibrutinib for 1st relapse after ASCT. POD24 was defined as progressive disease in less than 24 months after ASCT. Results 66 patients met the inclusion criteria (Table 1) relapsing at a median of 25 months (range 15-33) post ASCT. Thirty-two patients progressed in less than 24 months after ASCT. Ibrutinib was started at a median of 30 days after relapse (range 10-54). Overall response rate (ORR) was 74% [32 (48%) achieving CR and 18 (27%) PR]. The median duration of response was 10.1 months (available for 28 patients). There were no significant differences in the duration of response to ibrutinib for patients with POD24 (median: 10.4 months, IQR 4.0-15.4) compared to POD after 24 months or more (POD≥24) [(median 9.8 months, IQR 6.5-20.7) p=0.9]. Relapse after/during ibrutinib occurred in 21 patients (33%) at a median of 12 months (range 1-34). 13 of those patients were on ibrutinib at the time of relapse and the remaining 8 after ibrutinib had been stopped for a SCT or because of toxicity. Ibrutinib therapy continues at last follow-up in 23 (35%) patients. Ibrutinib was stopped for the following reasons: 16 patients subsequent SCT, 13 relapse, 5 toxicity (cytopenia, infection, tachycardia, hepatitis and poor tolerance, 1 case each), 9 other/unknown reasons. Second SCT was undertaken in 23 patients (22 alloSCT, 1 ASCT), 16 of whom were in CR/PR after only ibrutinib at the time of relapse. For alloSCT recipients, the donor was MUD in 11, MSD in 5 and mismatch related in 6. The majority (n=19) had reduced intensity conditioning. 50% of the patients developed acute GvHD and 50% chronic GvHD (3 extensive). With a median follow up of 17 months post alloSCT, 18 (63%) are in remission. There were no significant differences in PFS (p=0.173) or OS (p=0.336) post alloSCT for patients with POD24 and POD≥24. At last follow up (median follow-up of 22 months after starting ibrutinib), 35 (71%) patients were in CR and 4 (8%) in PR. 17 patients have died; the most common reason was MCL (14 patients), 2 deaths were secondary to alloSCT toxicity and in 1 case the cause of death was unknown. 2-year OS after starting ibrutinib was 72% (69% for alloSCT patients) and 2-year PFS 62%. PFS after starting ibrutinib was significantly better for patients with POD≥24 compared to those with POD24 (72% vs. 53% at 2 years post ASCT, p=0.017) and this translated to an OS benefit (80% vs. 68% at 2 years post ASCT, p=0.019) (figures 1 and 2). Conclusion Ibrutinib therapy did not overcome the poor outcome for patients with POD24 after first line therapy and although there was a high ORR to ibrutinib the median duration of response is only 10.1 months. AlloSCT should therefore be undertaken if possible, in our retrospective cohort of patients it appeared to overcome the poor prognosis of POD24 patients. Disclosures Hunter: Jazz pharamceuticals: Honoraria, Other: speaker fees, Meeting attendance support; Novartis: Honoraria, Other: speaker fees; celegene: Other: Meeting attendance support. Peggs:Autolus: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Speakers Bureau. Foà:Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees. Pillai:Celgene: Honoraria. Mufti:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cellectis: Membership on an entity's Board of Directors or advisory committees, 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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Impact of Rituximab in the Clinical Outcomes of Hairy Cell Leukemia: A Retrospective Single-Institution Analysis

Blood ◽

10.1182/blood-2019-129028 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1542-1542

Author(s):

Kristen Gonter-Aubin ◽

Daniel Alan Kerr ◽

Ashley Rose ◽

Thanh Lana Nguyen ◽

Julio C. Chavez ◽

...

Keyword(s):

Board Of Directors ◽

Response Rate ◽

Hairy Cell ◽

Single Institution ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy

Background: Hairy cell leukemia (HCL) is an indolent mature B-cell disorder that comprises ~2% of all leukemias. Purine nucleoside analogues (PNA) such as cladribine and pentostatin remain the standard initial treatment with high response rate, however frequent late relapses occur. The addition of rituximab (R) has shown efficacy as a single agent and in combination in the first- and second-line settings . Recent data suggests that the addition of R to PNA increased the minimal residual disease (MRD) negative (neg) and duration of response (DOR) when compared to PNA alone. In this study, we examined the impact of rituximab (R) in the long term outcomes of HCL from a single institution experience. Methods: An IRB-approved retrospective analysis was performed including patients with HCL or HCL-variant who were seen at Moffitt Cancer Center between 1/2000 and 2/ 2019. Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints included overall response rate (ORR). Complete Remission (CR) was determined based off of accepted criteria of Hgb > 11gr/dL, platelets > 100,000/µL and ANC > 1500/µL. Statistical comparisons and survival analyses were performed using SPSSTM Statistics and GraphPad PrismTM. Results: We identified 124 cases with available treatment data and follow up (82 HCL, 15 CD25-negative HCLv). The median follow-up was 72 months. The median age was 57 years (27 - 89+). The 5 and 10 year OS was 97% and 91%, respectively, with 2 deaths reported secondary to HCL or complications from HCL. The median PFS for all patients receiving first-line therapy was 92 months. Clinical risk factors present at diagnosis that were independently associated with worse PFS after first-line therapy were weight loss (HR 2.27, p = 0.057), recurrent infections (HR 2.50, p=0.009) and splenomegaly (HR 1.87, p=0.047),, hemoglobin less than 11 gr/dL (HR 3.12, p=0.016), and negative CD25 (HR 2.14, p=0.055). In multivariate analyses, negative CD25, recurrent infections and Hgb < 11 gr/dL were associated with worse PFS after first line therapy (p = 0.002). Most patients received PNA alone or PNA+R (96 and 18, respectively) as first line with a higher CR rate in the PNA+R group (100% vs 71%) and a higher median PFS for [not reached (NR) and 82 months, respectively, p = 0.165] with 2 relapses in the PNA+R group (both at 30 months). In the 2nd line setting, PNA+R (n = 11) was also associated with a higher CR rate than PNA alone (n = 22, 82% vs 64%) with only 1 relapse in the PNA+R group at 97 months. The median PFS for 2nd line PNA+R vs 2-CdA was 97 and 43 months, respectively (p = 0.253). Conclusions: In this study, we report a large, retrospective, single-institution dataset of HCL and HCLv patients with long-term follow-up. The addition of R may improve the PFS in patients with HCL in the first and 2nd -line settings however a longer follow up is needed. A recently described prospective randomized trial in the use of concomitant rituximab plus PNA has reported a higher MRD free CR in comparison with PNA alone but not PFS yet. Disclosures Chavez: Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Pinilla Ibarz:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy; TG Therapeutics: Consultancy; Bayer: Speakers Bureau; Sanofi: Speakers Bureau.

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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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Waldenström Macroglobulinemia in Young Patients Treated in the Modern Era: A Multi-Institutional Italian Study

Blood ◽

10.1182/blood-2019-125835 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1539-1539

Author(s):

Marzia Varettoni ◽

Angela Ferrari ◽

Alessandra Tedeschi ◽

Virginia Valeria Ferretti ◽

Rita Rizzi ◽

...

Keyword(s):

Board Of Directors ◽

The Elderly ◽

First Line ◽

Advisory Committees ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

Risk Patients ◽

Travel Grant

Background. Waldenström Macroglobulinemia (WM) is a rare indolent lymphoma typical of the elderly population, with a median age at diagnosis of 65-70 years and median overall survival of approximately 10 years. Age is the most important prognostic factor in WM, and unrelated mortality significantly impacts survival in elderly patients. The past two decades have witnessed important treatment advances in WM, with the introduction of anti-CD20 monoclonal antibodies in the early 2000s and of ibrutinib in more recent years. Less than 10% of WM patients are diagnosed at young age, and few studies have addressed their characteristics and outcome in the era of immunotherapy and targeted therapies. Here we report the presenting features, treatment and outcome of WM patients younger than 55 years diagnosed in 12 Hematologic Centers across Italy between 2000 and 2018. Patients and Methods. Diagnostic criteria were those established during the second International Workshop on WM (Owen et al, 2003) and were retrospectively applied to patients diagnosed before 2003. The overall survival (OS) observed in the study cohort was compared with the expected survival of the general Italian population matched by sex, age and calendar year. The expected survival estimates were derived from Italian life tables (Istituto Nazionale di Statistica, ISTAT). Results. The median age of patients included in the study was 50 years (interquartile range, IQR: 46-52). Their clinical characteristics at diagnosis are reported in Table 1. With a median follow-up of 5.6 years (IQR 3.1-9.1), 76 of 129 patients (59%) have been treated, at diagnosis (n=31, 41%) or after initial observation (n=45, 59%). The median treatment-free survival was 39 months. According to ISS-WM prognostic score, 58% were classified as low risk, 30% as intermediate risk and 12% as high risk. Frontline therapy included Rituximab in 71/76 patients (93%). Rituximab was associated with chemotherapy in 62 patients (82%), whereas 9 patients (12%) received a chemo-free induction. Five patients (7%) received chemotherapy only as first-line therapy (Table 2). The overall response rate (ORR) to induction therapy was 85%, including 39% CR+VGPR. Two patients received Rituximab maintenance for 2 years. The median progression-free survival (PFS) after first-line therapy was 76 months. Four of 76 patients (5%) received an autologous stem cell transplantation at relapse/progression. Overall, 14/76 patients (18%) received ibrutinib as first (n=2) or as subsequent line of therapy (n=12). During follow-up, 4/76 patients (5%) developed a solid cancer (bladder n=2, breast n=1, prostate n=1) and 2 a second hematologic cancer (chronic myelomonocytic leukemia n=1, secondary MDS n=1). Using a competing-risk model, accounting for death from any cause as the competing event, the cumulative incidence of second cancers was 2% at 5 years and 5.8% at 10 years. Three patients have died, 2 due to WM and 1 due to acute myeloid leukemia. The 5-and 10-year OS from diagnosis were 99% and 96% respectively. In a time-dependent survival analysis, considering therapy as a time-dependent covariate, the OS of treated and untreated WM patients was not significantly different (P = 0.162) (Figure 1). Among treated patients, the OS was significantly shorter in high-risk patients as compared with low- and intermediate-risk patients (5-year OS 85.7% versus 100%, P=0.018) (Figure 2). The OS of young WM patients was not significantly reduced as compared with age-, sex- and calendar year- matched general population (P > 0.05) (Figure 3). Conclusions. The presenting features of young WM patients resemble those typically described in the elderly WM population. Among treated patients, more than half are low-risk according to ISS-WM, confirming age as the most important prognostic factor. More than 90% of patients received Rituximab as part of the upfront treatment, mainly in combination with chemotherapy. Ibrutinib seems to be preferred over autologous stem cell transplantation in the relapsed/refractory setting. The outcome of young WM patients treated in Italy in the contemporary era was excellent in terms of both PFS and OS, with a life expectancy not significantly reduced as compared with the general population. Figure 1 Disclosures Varettoni: Gilead: Other: travel expenses; Janssen: Consultancy; Roche: Consultancy; ABBVIE: Other: travel expenses. Tedeschi:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen spa: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SUNESIS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy. Benevolo:Novartis Pharmaceuticals: Consultancy. Del Fabro:Janssen: Consultancy. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Arcaini:Gilead Sciences: Research Funding; Celgene: Speakers Bureau; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy.

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

Blood ◽

10.1182/blood-2019-124192 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5263-5263

Author(s):

Karin Hohloch ◽

Christine Windemuth-Kieselbach ◽

Pier Luigi Zinzani ◽

Roberto E. Cacchione ◽

Wojciech Jurczak ◽

...

Keyword(s):

Follicular Lymphoma ◽

Mantle Cell Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Cell Lymphoma ◽

Primary Therapy ◽

First Line ◽

Advisory Committees ◽

Mantle Cell

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

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Poor Outcomes Among Patients Failing Dose-Adjusted EPOCH in Aggressive Lymphoma: A Collaborative, Retrospective Study

Blood ◽

10.1182/blood.v126.23.1518.1518 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1518-1518 ◽

Cited By ~ 1

Author(s):

Jackie Vandermeer ◽

Allison M Winter ◽

Ajay K. Gopal ◽

Ryan D. Cassaday ◽

Brian T. Hill ◽

...

Keyword(s):

B Cell ◽

Board Of Directors ◽

Salvage Therapy ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

First Line ◽

Advisory Committees ◽

First Line Therapy

Abstract Introduction Among patients with aggressive B-NHL who fail RCHOP, about half respond to standard salvage regimens and may proceed to curative-intent, transplant-based therapy. However, whether pts failing more intensive regimens such as dose-adjusted, infusional EPOCH benefit from standard salvage regimens is unclear. We hypothesized that such patients comprise a higher-risk cohort, facing inferior response rates and outcomes using standard salvage regimens. We undertook a collaborative study to assess response rates and survival among pts failing EPOCH for aggressive B-NHL, to inform patient management and design of clinical trials in this setting. Methods Pharmacy records and institutional databases were queried, identifying pts receiving EPOCH over the last 10 years at the University of Washington/SCCA and the Cleveland Clinic Foundation, for combined analysis. Under IRB approval, patient characteristics, histology, outcome with EPOCH, time to EPOCH failure, response to salvage, and overall survival were analyzed. Diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, B-cell-lymphoma unclassifiable, HIV-associated B cell lymphoma, and transformed B cell non-Hodgkin lymphoma were included. Pts receiving <2 cycles EPOCH, or who had inadequate follow-up (<3 months), were excluded. Failure of EPOCH was defined as failure to respond or progression during therapy, need for initiation of salvage therapy, or death during therapy of any cause. Adverse events or treatment change due to toxicity were not included in the definition of failure. JMP 11 was used to generate kaplan-meier survival estimates. Results 124 pts with aggressive B-NHL receiving EPOCH were identified. 54 had not relapsed, and among 70 remaining da-EPOCH failures, 37 met the above inclusion criteria. Median age was 55. 27% were female, and 23 received EPOCH as first-line therapy. All but 3 received rituximab with EPOCH. Histologies were primarily DLBCL in 22/37 (60%) and BCL-U in 12/37 (32%) carrying a MYC translocation; most of these harbored additional translocations in BCL2 and/or BCL6 (10/12). However, data regarding MYC rearrangement was not available for all pts. 2 had HIV-associated B-NHL and 3 had PMBCL. With 18 months follow up, the median time to EPOCH failure was 5 months. Only 3 EPOCH failures occurred late (>12 months). Median OS from the date of EPOCH failure was 10 months (Figure 1). Those receiving EPOCH as first-line therapy (23) had a median OS of 14 months from EPOCH failure, as opposed to 4 months for those receiving EPOCH as salvage therapy (log-rank p=.01). Salvage chemotherapy regimens after EPOCH were diverse, and generally ineffective; 6/28 (21%) regimens produced a response (Table 1). Among patients failing EPOCH within a year, platinum-containing salvage (RICE/RDHAP) was effective in only 2/13 patients (15%). 9 patients did not receive any salvage, most of whom died or proceeded to palliative measures and/or hospice care. Conclusions A relatively low overall response rate (21%) was observed in this retrospective analysis of patients failing EPOCH. Analogous to early RCHOP failure in the CORAL study, those failing EPOCH within a year may face inferior outcomes with platinum-based salvage therapy. While combined from two institutions, our data represent a modest sample size and require confirmation. If verified, examination of mechanisms of resistance to EPOCH, and selecting EPOCH failures for clinical trials of novel targeted therapies and transplant-based approaches, may prove critical. Table 1. Salvage Therapy for REPOCH failures Regimen: response/total number treated Notes Response to any salvage: 6/28 (21%) Some patients received more than 1 chemo salvage; responses were tabulated per regimen. RICE: 4/12 2/3 alive post transplant(1 auto 1 allo; 1 declined transplant and survived; 1 died) RDHAP: 1/6 Gemcitabine-based: 0/5 HyperCVAD (Part A and/or B): 1/5 Survivor had CNS only relapse, received regimen B and transplant 9- received no systemic treatmen; most died or proceeded to palliative measures and/or hospice Figure 1. Figure 1. Disclosures Gopal: Gilead: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Emergent/Abbott: Research Funding; Sanofi-Aventis: Honoraria; Seattle Genetics: Consultancy, Honoraria; BioMarin: Research Funding; Piramal: Research Funding; Janssen: Consultancy; Millenium: Honoraria, Research Funding; BMS: Research Funding; Merck: Research Funding. Hill:Seattle Genetics: 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; Pfizer: Consultancy, 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. Till:Roche/Genentech: Research Funding; Pfizer: Research Funding.

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

Blood ◽

10.1182/blood-2021-146722 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2552-2552

Author(s):

Franck E. Nicolini ◽

Vincent Alcazer ◽

Stephanie Dulucq ◽

Sandrine Hayette ◽

Jean-Michel Cayuela ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Chronic Phase ◽

Median Dose ◽

First Line ◽

Advisory Committees ◽

French Group ◽

Treatment Free Remission ◽

The Impact

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

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Autoimmune Cytopenias Following Alemtuzumab-Induced Renal Transplant: Clinical Features and Treatment Outcomes

Blood ◽

10.1182/blood-2018-99-115258 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2434-2434

Author(s):

Elisa Lucchini ◽

Asad Luqmani ◽

Maria Atta ◽

Simona Deplano ◽

Mark Layton ◽

...

Keyword(s):

Renal Transplant ◽

Relapse Rate ◽

Rapid Onset ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Duration Of Response ◽

Autoimmune Cytopenias

Abstract Background: The anti-CD52 monoclonal antibody alemtuzumab (Alem) induces a rapid-onset, profound and long-lasting depletion of lymphocytes: B cells recover within 12 months, while T cell recovery is still incomplete after 30 months. Alem is used as induction therapy for solid organ transplantations, including renal. Autoimmune complications following Alem include thyroid disorders (20-30%), immune thrombocytopenia (ITP) (2-3%), and autoimmune hemolytic anemia (AIHA) and autoimmune nephropathies (< 1%). Methods: we retrospectively analyzed 41 patients (pts) attending the Haematology Clinic at Hammersmith Hospital (HH), who developed autoimmune cytopenias (ITP or AIHA) after an Alem-induced renal transplant. The autoimmune cytopenia was defined as a rapid onset of isolated thrombocytopenia and/or anemia without other explanation. For ITP, complete response (CR) and response (R) were defined according to IWG standard criteria (Rodeghiero,Blood,2009). For AIHA, CR was defined as a stable Hb level >120 g/L, no transfusion requirement and no signs of hemolysis; partial response (PR) as a rise in Hb levels >20 g/L, without transfusion requirement. The study aim is to report clinical features and treatment outcomes of these 41 pts. Results: Between 1/11/05 and 14/12/16, 1431 pts received an Alem-induced renal transplant at HH. 34 (2.3%) developed ITP and 7 (0.48%) AIHA; 28 (68%) pts were males. Median age at renal transplant was 48 (range 20-69) years. The cytopenia developed a median of 35 months (range 6-161) after Alem administration. Median lowest platelet count was 5.5x109/L (range 0-41) and median nadir of hemoglobin (Hb) was 58 g/L (range 35-65). ITP pts: 2 pts achieved spontaneous CR. Of the remaining 32, 91% received steroids, IVIG or both as first line therapy, with an overall response rate (ORR) of 62%. 10 pts (31%) maintained the response without any further treatment. 22 pts required second line therapy, 11 required ≥ 3 lines of treatment. Treatments included: thrombopoietin receptor agonists (TPO-RA), rituximab (RTX), MMF and/or a combination. TPO-RA were used 15 times, with an ORR of 80%, a relapse rate of 33% and a median duration of response (DOR) of 22 months (range 3-48); 10/12 pts (83%) who responded to TPO-RA, discontinued treatment after a median of 64 days (range 7 - 528): 6 maintained the response after discontinuation. RTX was used 10 times, with an ORR of 90%, a relapse rate of 22% and a median DOR of 27 months (range 3 - 83). A combination of RTX and TPO-RA was used 7 times, with an ORR of 71%, a relapse rate of 40% and a median duration of response (DOR) of 5 months (range 2-44); the 5 responders discontinued treatment after a median of 49 days (range 14-462): 3/5 maintained their response. After a median follow-up of 38 months (range 3-96), all ITP pts maintained a response (91% CR and 9% R); 4 were still on treatment (2 TPO-RA and 2 MMF). AIHA pts: 6 of 7 (86%) pts with AIHA received first line steroids +/- IVIG with an ORR of 67%. 4 pts needed second line therapy: all received RTX with an ORR of 50%. 2 pts needed ≥ 3 lines of therapy. After a median follow-up of 68 months (range 27-102) all AIHA pts maintained a response (57% CR and 43% PR), without any ongoing treatment. Adverse events: 33 pts (80%) experienced 1 or more adverse events (AEs): 25 cardiovascular (including 14 thrombosis), 21 infections (16 grade ≥3), 5 steroid-induced diabetes, 3 graft failures, 10 malignancies (6 solid tumors and 4 PTLD). 6 of the ITP pts also developed AIHA (Evans syndrome). 3 ITP pts died. Conclusions: ITP and AIHA represent important complications of Alem-induced renal transplant. Response rates after first-line therapy for ITP were comparable to primary ITP (30%). However, long-term response rate, sustained response to RTX and the proportion of pts able to continue in remission after discontinuing TPO-RA are higher than seen with primary ITP. Recovery from cytopenias may occur in conjunction with T cell reconstitution post Alem (this is under investigation). The large majority of AEs were related to multifactorial heavy immunosuppression and increased thrombotic risk distinguishing this group of pts. Hence for ITP and AIHA, steroids should be limited, as they are curative in only a few pts and burdened by many side effects. Both RTX and a short course of TPO-RA appear valid options, but the choice should be driven by the individual balance between thrombotic and infectious risks versus persistence of cytopenias. Disclosures Cooper: Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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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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