Real-World Outcomes for Standard-of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Abstract Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p<0.001), being male (p=0.001), older age (p<0.001), shorter duration of prior lines (p<0.001), shorter time to progression in prior line (p=0.025), and higher LDH levels (p<0.002) were prognostic for worse outcomes for both OS (Figure 1) and PFS. Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of <10 months. A wide variety of treatment regimens used in clinical practice confirm the absence of a clear standard-of-care in this patient population. The literature also confirms that these poor outcomes observed in Belgium, for this subset of MM patients, are similar in other countries. These real-world data highlight the high unmet medical need in this patient population and critical need for new and effective treatment options. MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

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An Ongoing, Observational Cohort Study in Multiple Myeloma (PREAMBLE): Preliminary Efficacy Analyses in Patients with 1 Line of Prior Therapy

Blood ◽

10.1182/blood.v128.22.2403.2403 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2403-2403

Author(s):

Brian Durie ◽

David J Kuter ◽

Catherine Davis ◽

Teresa Zyczynski ◽

Hartmut Goldschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Treatment Outcomes ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Hematologic Malignancy ◽

Research Assessment ◽

Advisory Committees ◽

Prior Therapy

Abstract Introduction: Multiple myeloma (MM) is an incurable hematologic malignancy associated with high disease burden and relapse rates. In recent years, several treatment options for MM have become available that have improved patient outcomes. However, robust data on real-world treatment outcomes associated with these MM treatments are sparse. PREAMBLE (Prospective REsearch Assessment in Multiple myeloma: an oBservationaL Evaluation; NCT01838512) is an ongoing multinational observational study that aims to increase understanding of real-world clinical effectiveness of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and combination therapy for relapsed/refractory MM (RRMM). Here, we present preliminary efficacy analyses on data from patients with 1 line of prior MM therapy both with and without prior transplantation experience. Methods: Eligible patients had a confirmed diagnosis of RRMM with 1 prior treatment and started treatment with an IMiD, PI, or IMiD+PI 90 days prior/30 days following study enrollment. Patient data were collected at each healthcare provider visit for a follow-up period of 3 years. Vital status was recorded every 6 months for all patients. Response rates (defined as minimal response or better) were assessed using cumulative incidence function, with progression as competing risk. Time in response, progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Results: Of 855 treated patients, 367 (43%) had 1 prior line of therapy (median age 70 years, 56% male). In this group, 71 (19%) had refractory disease, with even distribution among International Staging System stages I, II, and III. Index therapy was IMiD (n=193, 53%), PI (n=148, 40%), or IMiD+PI (n=26, 7%). At data cut-off (April 2016), median (Q1-Q3) follow-up was 16.7 (9-27) months, and 225 (61%) patients were still on study; the most common reasons for discontinuation were death or entering into a randomized clinical trial. Discontinuation was attributed to death for 92 (25%) patients; 69 (75%) of these deaths were due to disease progression. Approximately one-third of patients (128/367; 35%) had prior transplantation experience: 5% of patients had 2 prior transplantations, 99% of transplantations were autologous, and 83% were received after frontline (first) therapy. In patients without transplantation experience (n=238), the response rate (95% CI) was 46% (39-53) at 6 months, 58% (50-65) at 12 months, and 60% (53-67) at 18 months, versus 43% (34-53), 60% (50-70), and 60% (50-70), respectively, in those with prior transplantation. Median time in response was 14.6 months in patients without prior transplantation versus 20.3 months in those with prior transplantation. In patients with and without prior transplantation, time in response was longer in patients who had received an IMiD as index therapy (Table). Median PFS was 11.5 months in patients without transplantation and 14.1 months in those with transplantation; PFS rates (with/without prior transplantation) was: 6 months, 71%/67%; 12 months, 56%/49%; 18 months, 41%/32%. OS rate at 12 months was 81% in patients without prior transplantation and 82% in those with prior transplantation. In patients (≥6 months on study) who responded within 6 months, OS rate (IMiD/PI cohorts) was: 6 months, 100%/100%; 12 months, 93%/91%; 18 months, 85%/78%. In patients (≥6 months on study) who progressed within 6 months, OS rate (IMiD/PI cohorts) was: 6 months, 100%/100%; 12 months, 84%/69%; 18 months, 56%/64%. Conclusions: In patients with MM and 1 line of prior therapy either with or without prior transplantation experience, approximately 45% achieved a response, with approximately 40% of these patients maintaining their response at 18 months. Regardless of index therapy type or prior transplantation experience, loss of response was observed over time, highlighting the continuing unmet medical need in RRMM. Collectively, these data exemplify the importance of novel therapies that have potential to provide durable responses and improve treatment outcomes for patients with RRMM. Further analyses exploring any impact of prior transplantation and type of frontline therapy on treatment outcomes with subsequent lines of therapy are ongoing, and will be included in the final presentation. Study support: Bristol-Myers Squibb (BMS). Medical writing assistance was provided by K Rees, of Caudex, funded by BMS. Disclosures Durie: Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Kuter:Amgen: Consultancy; Eisai: Consultancy; Genzyme: Consultancy; GlaxoSmithKline: Consultancy; ONO: Consultancy; Pfizer: Consultancy; Shionogi: Consultancy; Shire: Consultancy; 3SBios: Consultancy; Bristol-Myers Squibb: Research Funding; Protalix: Research Funding; Rigel: Research Funding. Davis:Bristol-Myers Squibb: Employment. Zyczynski:Bristol-Myers Squibb: Employment. Goldschmidt:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Honoraria, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Vij:Amgen: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Consultancy; Takeda: Honoraria, Research Funding; Novartis: Honoraria; Karyopharm: Honoraria. Popov:Bristol-Myers Squibb: Consultancy. Cella:Abbvie, Inc.: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bayer Pharmaceuticals, Inc.: Consultancy, Research Funding; Alexion, Inc., Astellas, Biogen Idec, Celgene, Clovis Oncology, Inc., Daiichi Sankyo, Eli Lilly, Evidera, Inc., Exelixis, Fiborgen, Genetech, Helsinn Therapeutics, Inc., Immunogen, Ipsen Pharma, Janssen, Lexicon Pharmaceuticals, Inc., Merck, Novartis, Onc: Consultancy, Research Funding; Facit.org: Other: President; Bristol-Meyers Squibb: Consultancy, Research Funding. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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One Line Does Not Make a Picture: Real-World Cost-Effectiveness Of Multiple Myeloma Treatments Using a Full Disease Model

Blood ◽

10.1182/blood.v122.21.2930.2930 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2930-2930

Author(s):

Hedwig M Blommestein ◽

Silvia GR Verelst ◽

Saskia de Groot ◽

Peter C. Huijgens ◽

Pieter Sonneveld ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Cost Effectiveness ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Disease Model ◽

Real World Data ◽

Advisory Committees ◽

Treatment Pathways

Abstract Background As with many types of cancer, treatment of multiple myeloma (MM) is characterised by sequential treatment lines consisting of innovative expensive drugs such as thalidomide, bortezomib and lenalidomide. While the cost-effectiveness of single treatments has been studied, a full disease model evaluating treatments sequentially is currently lacking. Therefore, we aimed to take a look at the big picture and calculate real-world costs and effects for commonly used treatment pathways for MM. Methods We developed a patient-level simulation (PLS) model for elderly (>65) MM patients diagnosed since 2004. Real-world data (N=621) including patient and disease characteristics, treatment information and outcomes as well as resource use was obtained from the Population based HAematological Registry for Observational Studies, PHAROS. Based on this information, a patient population was simulated. Parametric survival models including patient characteristics such as age, performance status, comorbidities, laboratory values and treatment were used to predict overall survival of commonly used treatment pathways. Five treatment categories were distinguished; Melphalan/Prednison, Thalidomide based regimens, Bortezomib based regimens, Lenalidomide based regimens and Other regimens not including a novel agent. Monthly costs, per treatment per line, were calculated based on real-world data. The sensitivity of parameters was explored through sensitivity analyses. Results Mean age of our simulated population was 76 [SD: 6.25, Range 66-93] and 19 commonly used treatment pathways were observed. Average total costs from diagnosis till death ranged from $54,200 [SD: $10,990] (Melphalan/Prednison-Thalidomide-Other) to $172,346 [SD: $27,887] (Lenalidomide-Bortezomib-Other) while overall survival ranged from 29 [SD: 1.02] to 50 [SD 1.75] months for Melphalan/Prednison-Bortezomib-Lenalidomide and Lenalidomide-Bortezomib-Other, respectively. Total costs were especially induced by drug costs and inpatient hospital days. Substantial variation among the treatment pathways was observed with drug costs ranging from 7% ($3,980) of the total costs for Melphalan/Prednison-Thalidomide-Other compared to 53% ($88,058) of the total costs for Lenalidomide-Bortezomib-Thalidomide. In addition, inpatient day costs ranged from 68% ($37,113) of total costs for Melphalan/Prednison-Thalidomide-Bortezomib to 25% ($41,347) of the total costs for Lenalidomide-Bortezomib-Thalidomide. Costs per quality-adjusted-life-year (QALY) were between $29,060 [SD: $5,623] (Melphalan/Prednison-Thalidomide-Other) and $56,179 [SD: $9,190] (Lenalidomide-Bortezomib-Other). In addition to the 19 treatment pathways, we calculated the total costs and overall survival of treatment as observed in daily clinical practice, $79,203 [SD: $12,001] and 32 [SD: 1.33] months, respectively. Compared to real-world prescription, survival could be improved at a cost of $48,543 per QALY and $31,902 per life-year gained (Lenalidomide-Thalidomide-Bortezomib). Conclusion Real-world costs and effects of 19 treatment pathways for MM patients were calculated and revealed that real-world treatment could be improved at a cost of $48,543 per QALY and $31,902 per life-year gained. Our PLS model proved to be a reliable and robust approach to study entire treatment pathways for MM. Disclosures: Sonneveld: Jansssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

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Clinical Outcomes of Patients with Newly Diagnosed Multiple Myeloma Receiving Triplet Therapy in the Connect MM® Disease Registry

Blood ◽

10.1182/blood.v126.23.4229.4229 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4229-4229

Author(s):

Jatin J. Shah ◽

Rafat Abonour ◽

Mohit Narang ◽

Jayesh Mehta ◽

Howard R. Terebelo ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Newly Diagnosed ◽

Employment Equity ◽

Advisory Committees ◽

Risk Of Death ◽

Equity Ownership ◽

Triplet Regimen

Abstract Introduction: Triplet therapies are used for treatment (Tx) of both transplant-eligible and -ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Actual patterns and outcomes of Tx are not fully understood. Connect MM® is the first and largest multicenter, US-based, prospective observational cohort study designed to characterize Tx patterns and outcomes for pts with NDMM. This analysis describes demographic and disease characteristics of pts who received triplet Tx as an induction regimen and for whom transplant was or was not intended. The analysis explores the relationship of these factors with overall survival (OS) and other efficacy endpoints. Patients and Methods: Pts aged ≥ 18 y with NDMM within 60 days of diagnosis were eligible for enrollment regardless of disease severity, medical history, or comorbidities. Data including transplant intent (yes/no) was collected at baseline; follow-up data was collected quarterly thereafter. Based on the initial intent, 2 groups were identified: patients with intent to transplant who received transplant (TT) and pts with no intent to transplant who did not receive a transplant (NT). Triplet Tx was defined as the combination of ≥ 3 concurrent therapeutic agents in the first course of Tx (within 56 days of study entry). KM analysis adjusted for age was conducted for OS. Because decisions on use of transplant and triplet therapy are influenced by multiple factors, a multivariable Cox regression analysis was performed to evaluate the contribution of the triplet therapy (yes/no) to OS and was adjusted for other variables, including age, comorbidities, and ISS staging. Results: Between September 2009 and December 2011, 1493 pts were enrolled. This analysis was on 1436 pts: 650 pts with transplant intent and 786 pts without transplant intent. The data cutoff date was November 30, 2014, and the median follow-up for overall survival (OS) was 33.8 mos. Of pts with transplant intent, 451 (69%) received transplant (TT) and 199 (31%) did not. Of pts without transplant intent, 62 (8%) received transplant and 724 (92%) did not (NT). The abstract focuses on TT and NT groups only. NT pts tended to be older and have more advanced ISS staging and higher β2-microglobulin levels than TT pts (Table). The most common triplet regimen given during the first course treatment (within 56 days) was lenalidomide, bortezomib, and dexamethasone (RVd). RVd was administered to 34% of the NT pts (76/225) and 59% of the TT pts (152/257). The most common non-triplet regimen was bortezomib and dexamethasone (Vd), which was given to 31% of NT pts (156/499) and 38% of TT pts (73/194). Within the NT group, pts given triplet Tx had a lower risk of death than those who did not receive triplet Tx (P = .0013). The multivariable analysis found triplet Tx to be associated with a 36% reduced risk of death (hazard ratio [HR] = 0.64 [95% CI, 0.50-0.82]; P = .001). ISS disease stage (HR = 1.43 [95% CI, 1.21-1.69]; P < .001) and history of diabetes (HR = 1.38 [95% CI, 1.08-1.78]; P = .012) were negative prognostic factors for OS. Within the TT group, pts who received triplet Tx did not attain an OS benefit (P = .8993), and no baseline characteristics were significantly associated with OS. These results may be limited by other factors not considered that may have influenced physicians' choice of treatment, including the use of maintenance therapy and a short follow-up period of 33.8 months. Conclusions: Triplet Tx as a first regimen is associated with longer OS in pts without transplant intent who did not receive a transplant. RVd and Vd were the most common first Tx regimens, respectively. Continued follow-up of these pts and enrollment of an additional cohort will provide additional data with mature follow-up. Table 1. Table 1. Disclosures Shah: Bristol-Myers Squibb: Research Funding; Array: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: 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; Millenium: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Research Funding, Speakers Bureau. Narang:Celgene: Speakers Bureau. Mehta:Celgene Corporation: Speakers Bureau. Terebelo:Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacylics: 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. Gasparetto:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Honoraria, Other: Export Board Committee, Speakers Bureau. Toomey:Celgene: Consultancy. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Srinivasan:Celgene Corporation: Employment, Equity Ownership. Larkins:Celgene Corporation: Employment, Equity Ownership. Nagarwala:Celgene Corporation: Employment, Equity Ownership. Rifkin:Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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

Blood ◽

10.1182/blood.v128.22.5885.5885 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5885-5885

Author(s):

Taiga Nishihori ◽

Claudio Anasetti ◽

Rachid Baz ◽

Jose L Ochoa-Bayona ◽

Kenneth H. Shain ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Hematopoietic Cell Transplantation ◽

Advisory Committees ◽

Allogeneic Hct ◽

Genetics Research ◽

Gvhd Prophylaxis ◽

Unrelated Donors

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

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Real-World Outcomes for Pediatric and Young Adult Patients with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL) Treated with Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Blood ◽

10.1182/blood-2021-146393 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 428-428

Author(s):

Samuel John ◽

Michael A. Pulsipher ◽

Amy Moskop ◽

Zhen-Huan Hu ◽

Christine L. Phillips ◽

...

Keyword(s):

Clinical Trial ◽

T Cell ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Ad Hoc ◽

Age Groups ◽

Advisory Committees ◽

Advisory Boards

Abstract Background: Tisagenlecleucel is an autologous CD19-directed T-cell immunotherapy indicated in the USA for treatment of patients up to 25 years (y) of age with B-cell ALL that is refractory or in second or later relapse. Overall response rate was 82% with 24 months' (mo) follow-up in the registrational ELIANA trial [Grupp et al. Blood 2018]; pooled data from ELIANA and ENSIGN revealed similar outcomes upon stratification by age (<18y and ≥18y) [Rives et al. HemaSphere 2018]. Early real-world data for tisagenlecleucel from the CIBMTR registry reported similar efficacy to ELIANA with no new safety signals [Pasquini et al. Blood Adv 2020]. Outcomes are reported here for patients who received tisagenlecleucel in the real-world setting, stratified by age (<18y and ≥18y). Methods: This noninterventional prospective study used data from the CIBMTR registry and included patients aged ≤25y with R/R ALL. Eligible patients received commercial tisagenlecleucel after August 30, 2017, in the USA or Canada. Age-specific analyses were conducted in patients aged <18y and ≥18y at the time of infusion. Efficacy was assessed in patients with ≥12mo follow-up at each reporting center and included best overall response (BOR) of complete remission (CR), duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). Safety was evaluated in all patients who completed the first (100-day) assessment. Adverse events (AEs) of interest - including cytokine release syndrome (CRS) and neurotoxicity - were monitored throughout the reporting period. CRS and neurotoxicity were graded using the ASTCT criteria. Results: As of October 30, 2020, data from 451 patients were collected, all of whom received tisagenlecleucel. The median time from receipt of leukapheresis product at the manufacturing site to shipment was 27 days (interquartile range: 25-34). Patients aged ≥18y appeared to have greater disease burden at baseline than those aged <18y, indicated by lower rates of morphologic CR and minimal residual disease (MRD) negativity prior to infusion. Older patients were also more heavily pre-treated before infusion. All other patient characteristics at baseline were comparable between the two groups (Table 1). In the efficacy set (median follow-up 21.5mo; range 11.9-37.2; N=322), BOR of CR was 87.3% (95% CI 83.1-90.7); MRD status was available for 150 patients, of whom 98.7% were MRD negative. Median DOR was 23.9mo (95% CI 12.3-not estimable [NE]), median EFS was 14.0mo (9.8-24.8) and median RFS was 23.9mo (13.0-NE); 12mo EFS and RFS were 54.3% and 62.3%, respectively. For OS, the median was not reached. Efficacy outcomes were generally similar across age groups (Table 1). In the safety set (median follow-up 20.0mo; range 2.6-37.2; N=400), most AEs of interest occurred within 100 days of infusion. Any-grade CRS was observed in 58.0% of patients; Grade ≥3 in 17.8%. Treatment for CRS included tocilizumab (n=113; 28.3% of all patients) and corticosteroids (n=31; 7.8%). Neurotoxicity was observed in 27.3% of patients; Grade ≥3 in 10.0%. Treatment for neurotoxicity included tocilizumab (n=17; 4.3% of all patients) and corticosteroids (n=28; 7.0%). During the reporting period, 82 (20.5%) patients died; the most common cause of death was recurrence/persistence/progression of primary disease. CRS and chimeric antigen receptor (CAR)-T cell-related encephalopathy syndrome were the primary cause of death in 2 patients and 1 patient, respectively. Overall, safety data were similar across age groups, although more patients aged ≥18y experienced any-grade CRS or neurotoxicity and were subsequently treated (Table 1). Conclusions: Updated registry data for pediatric and young adult patients with R/R ALL treated with tisagenlecleucel revealed that patients aged ≥18y had a greater disease burden and were more heavily pre-treated at baseline than patients aged <18y. The overall efficacy and safety profiles of commercial tisagenlecleucel reflected those observed in the clinical trial setting [Grupp et al. Blood 2018; Rives et al. HemaSphere 2018] and were broadly consistent across age groups. Some important differences between the <18y and ≥18y groups were identified, which may point to challenges in timely identification and/or referral of older patients for CAR-T cell therapy. Figure 1 Figure 1. Disclosures Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Hu: Kite/Gilead: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Phillips: Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Margossian: Cue Biopharma, Inc.: Current Employment; Novartis: Other: Ad hoc Advisory Boards. Nikiforow: Kite/Gilead: Other: Ad hoc advisory boards; Novartis: Other: Ad hoc advisory boards; Iovance: Other: Ad hoc advisory boards; GlaxoSmithKline (GSK): Other: Ad hoc advisory boards. Martin: Novartis: Other: Local PI for clinical trial; Bluebird Bio: Other: Local PI for clinical trial. Rouce: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Pfizer: Consultancy. Tiwari: Novartis Healthcare private limited: Current Employment. Redondo: Novartis: Current Employment. Willert: Novartis: Current Employment. Agarwal: Novartis Pharmaceutical Corporation: Current Employment, Current holder of individual stocks in a privately-held company. Pasquini: Kite Pharma: Research Funding; GlaxoSmithKline: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Grupp: Novartis, Roche, GSK, Humanigen, CBMG, Eureka, and Janssen/JnJ: Consultancy; Novartis, Kite, Vertex, and Servier: Research Funding; Novartis, Adaptimmune, TCR2, Cellectis, Juno, Vertex, Allogene and Cabaletta: Other: Study steering committees or scientific advisory boards; Jazz Pharmaceuticals: Consultancy, Other: Steering committee, Research Funding.

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Tracking Daratumumab Clearance Using Mass Spectrometric Approaches: Implications on M Protein Monitoring and Reusing Daratumumab

Blood ◽

10.1182/blood-2021-153209 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2707-2707

Author(s):

Nadine Abdallah ◽

David L Murray ◽

Angela Dispenzieri ◽

Prashant Kapoor ◽

Morie A. Gertz ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Plasma Cell ◽

Research Funding ◽

Univariate Analysis ◽

M Protein ◽

Urine Protein ◽

Advisory Committees ◽

Plasma Cell Disorders

Abstract Background: MASS-FIX is a screening method for serum and urine monoclonal proteins in multiple myeloma and related plasma cell disorders, which uses immunoglobulin enrichment coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). In addition to superior sensitivity over conventional gel-based techniques, MASS-FIX can distinguish therapeutic monoclonal antibodies (MoAb) from patient's M protein. As the utilization of therapeutic MoAbs increases, it is essential to understand the persistence pattern of these therapeutic antibodies in the serum. We designed this study to evaluate the duration of daratumumab detection by MASS-FIX in the serum of treated patients. Methods: We used a prospectively maintained database at Mayo clinic to identify patients with multiple myeloma and related plasma cell disorders who were treated with a daratumumab-containing regimen anytime during their disease course and had serial MASS-FIX data available after discontinuation of daratumumab. A univariate analysis was performed to assess for factors that may impact the clearance of daratumumab. Results: We included 125 patients with plasma cell disorders who received daratumumab as first or subsequent line of treatment between March 15 th, 2016, and March 4 th, 2020. The median age was 60.2 years and 57% were male. The most common diagnoses were multiple myeloma (70%) and light chain amyloidosis (18%). Daratumumab-based treatments were initiated after a median of 28.8 (IQR: 6.4-76.3) months from initial diagnosis. The most common regimen used was daratumumab, bortezomib and dexamethasone (23%); 26% underwent transplant after daratumumab-based induction. The median duration of treatment with a daratumumab-based regimen was 208 (IQR: 99-479) days. The median follow-up from the time of daratumumab discontinuation was 457 (95% CI: 346-NR) days. By last follow up, daratumumab was not detected by MASS-FIX in 93 (74%) patients but remained detectable in 32 (26%) patients. The median time from daratumumab discontinuation to disappearance of daratumumab by MASS-FIX was 160 (IQR: 107-233) days. On univariate analysis, the presence of ≥0.5 grams of urine protein was associated with earlier disappearance of daratumumab on MASS-FIX [risk ratio (RR): 2.0, P=0.02). The median time from daratumumab discontinuation to disappearance of daratumumab on MASS-FIX was 116 (95%CI: 76-160) days in patients with urine protein ≥0.5 grams and 203 (95%CI: 162-216) days in patients with urine protein <0.5 grams (P=0.02). There was no association between the time to disappearance of daratumumab by MASS-FIX and old age ≥70 (RR: 0.9, P=0.81], male gender (RR: 0.9, P=0.60), eGFR <60 (RR: 1.0, P=0.98), daratumumab schedule (every 1/2 weeks vs >2weeks) (RR: 1.0, P=0.97), treatment duration (<200 days vs ≥200 days) ( RR: 1.0, P=0.95), or transplantation status (RR: 1.0, P=0.98). Conclusion: The therapeutic monoclonal antibody daratumumab remains detectable in the serum of treated patients by MASS-FIX for several months after discontinuation and the duration varies between individual patients. This data has implications for diagnostic and monitoring testing and may provide guidance for reuse of daratumumab in clinical trials and practice. Proteinuria is associated with earlier disappearance of daratumumab by MASS-FIX and may have implications in patients with amyloidosis and monoclonal immunoglobulin deposition disease (MIDD). Further studies are needed to identify additional factors associated with the timing of disappearance. Disclosures Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Kapoor: Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Gertz: Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Dingli: Alexion: Consultancy; Novartis: Research Funding; Apellis: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; GSK: Consultancy. Kumar: Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Roche-Genentech: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Oncopeptides: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Carsgen: Research Funding; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

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Development of an Inclusive Risk Prognostic Index for Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood-2021-149213 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3789-3789

Author(s):

Ben A Derman ◽

Andrew J. Belli ◽

Ching-Kun Wang ◽

Eric Hansen ◽

Spencer S Langerman ◽

...

Keyword(s):

Older Adults ◽

Multiple Myeloma ◽

Board Of Directors ◽

Real World ◽

Prognostic Index ◽

Newly Diagnosed ◽

Advisory Committees ◽

C Statistic ◽

Equity Ownership

Abstract Background: Multiple myeloma (MM) risk stratification schemata such as the International Staging System (ISS) and Revised-ISS (R-ISS) were derived from clinical trial subjects made up predominately of younger White individuals with adequate renal function. It is unknown whether these prognostic indices are applicable to all patients with newly diagnosed (ND) MM, especially among Black individuals, older adults, and those with renal dysfunction. The R-ISS expanded on the ISS by including and serum lactate dehydrogenase (LDH) and high-risk cytogenetic abnormalities (HRCA) identified by fluorescence in-situ hybridization (FISH), but HRCA may not translate into poor prognosis for older adults and for Black individuals. We sought to create an inclusive risk prognostic index for NDMM using real-world data derived from electronic health records. Methods: De-identified NDMM patient-level data in the real-world setting was provided by COTA, Inc. 3000 patients were identified who met the inclusion criteria of NDMM between 2005 and 2020. Baseline diagnostic parameters available within 60 days before or after diagnosis were included. Progression free survival (PFS) was defined as the time from diagnosis to disease progression or death of any cause. Overall survival (OS) was defined as the time from diagnosis to death of any cause. Proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals for all-cause mortality. Age-adjusted univariate analyses identified variables significantly associated with OS, and continuous variables were dichotomized based on accepted cutoffs. Multivariate Cox models to identify the variables with the strongest association with OS were performed adjusting for age, sex, Black race, receipt of proteasome inhibitor and immunomodulatory imide during induction, autologous stem cell transplant within 1 year of diagnosis, ECOG performance status, and creatinine. An additive risk score was created with one point given to each significant variable. The risk score was then validated for PFS using the Multiple Myeloma Research Foundation's (MMRF) CoMMpass database (version IA15). Results: 3000 NDMM pts from the COTA, Inc. real-world database were initially evaluated, and a total of 689 NDMM pts had sufficient level of data to be included. The median follow-up time was 49.9 months (interquartile range (IQR) 29.1-76.2 months). Median age was 64 (IQR 32-86), including 44% age 65+. Of the 607 with reported race, 474 (78%) were White, 86 (14%) Black, 17 (3%) Asian, and 30 (5%) other. Of the 676 pts with reported serum creatinine (mg/dL), the median was 1 mg/dL (IQR 0.8-1.3) with 85 (13%) measuring >2 mg/dL. Examined peripheral blood variables were: calcium (corrected for albumin), albumin<3.5 mg/dL, beta2-microgloublin (B2M) >3.5 mcg/mL, LDH >250 U/L, hemoglobin <10 g/dL, M-spike >3 g/dL, and IgA isotype. Variables with significance using multivariate analysis at p<0.1 were: LDH>250 U/L, B2M >3.5 mcg/mL, hemoglobin <10 g/dL, and IgA isotype. These variables were simultaneously present in 558 patients. Patients were stratified into 3 groups: standard (std score = 0, n=186), intermediate (int score = 1-2, n=295), and high (score 3-4, n=77) risk. For this inclusive risk prognostic index (IRPI), the c-statistic was 0.61 for OS (HR 2.0, 95% CI 1.5-2.6, p<0.001) which compared favorably to the c-statistic for ISS (c=0.64, HR 1.8, 95% CI 1.5-2.2, p<0.001) and for R-ISS (c=0.63, HR 2.0, 95% CI 1.6-2.6). For the IRPI, median OS was 218 (std) vs 121.5 (int) vs 79.5 months (high). In comparison, median OS by ISS was 198.9 (stage I) vs 121.6 (stage II) vs 80.6 months (stage III), and by R-ISS: 198.9 (I) vs 121.6 (II) vs 79.5 months (III). Validation of the inclusive risk prognostic index (IRPI) using the MMRF CoMMpass database in 938 patients with all four criteria showed median PFS was 44 (std) vs 33 (int) vs 20.5 months (high). In comparison, median PFS by ISS was 45.9 (I) vs 31.5 (II) vs 20.5 (III) months. Median PFS by R-ISS was 50.1 (I) vs 32.7 (II) vs 19.1 (III) months. Conclusions: Employing real-world datasets that incorporate a more diverse patient population led to the generation of an inclusive risk prognostic index incorporating beta2-microgloublin, LDH, hemoglobin, and IgA isotype. This IRPI does not require bone marrow sampling, performs similarly to ISS and R-ISS in predicting PFS, and with datasets with longer follow-up may prove to predict OS. Figure 1 Figure 1. Disclosures Derman: Sanofi: Membership on an entity's Board of Directors or advisory committees. Belli: COTA, Inc.: Current Employment, Other: Equity ownership. Wang: COTA, Inc.: Current Employment, Other: Equity ownership. Hansen: COTA, Inc.: Current Employment. Jakubowiak: Amgen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Gracell: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

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Real World Outcomes of Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation and Receive Commercially-Available Salvage Therapy

Blood ◽

10.1182/blood-2019-128815 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2893-2893

Author(s):

Emily C. Ayers ◽

David J Margolis ◽

Phyllis A. Gimotty ◽

Daniel J. Landsburg

Keyword(s):

Board Of Directors ◽

Research Funding ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Current Therapy ◽

High Dose ◽

Cell Of Origin ◽

Advisory Committees ◽

Ecog Ps

Introduction: Salvage immunochemotherapy (IC) followed by high-dose chemotherapy with autologous stem cell transplantation (autoSCT) is standard-of-care second-line therapy (2L) for patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) deemed fit for autoSCT as per the CORAL study (J Clin Oncol. 2010 Sep 20;28(27):4184-90). Optimal therapeutic management of patients with R/R DLBCL who are autoSCT-ineligible is unknown. Here we describe the real-world outcomes of patients with R/R DLBCL who receive palliative intent 2L therapy in community and academic settings and do not receive autoSCT. Methods: This analysis includes de-identified patients from the nationwide Flatiron Health electronic health record-derived database with a histologic diagnosis of DLBCL and R/R disease after frontline IC who do not undergo autoSCT and receive treatment with either bendamustine-based therapy, gemcitabine-based therapy, lenalidomide, or ibrutinib. Patients receiving rituximab/ifosfamide/carboplatin/etoposide (R-ICE) and high-dose cytarabine-containing second-line therapies were excluded. Event free survival (EFS) was defined as the interval between the start of current therapy and start of subsequent therapy if needed, last follow-up on current therapy, or death on therapy. Overall survival (OS) was defined as the time between start of current therapy and death or last follow-up while alive. Results: A total of 250 patients were eligible for inclusion in 2L. Eight patients received autoSCT after gemcitabine therapy and were excluded from this analysis. Clinicopathologic characteristics at time of diagnosis include 56% male, 87% age >60, 55% ECOG performance status >1, 87% stage III-IV disease, 78% IPI >2, 56% germinal center (GCB) of those with cell of origin testing performed, 9% cMYC rearrangement positive when tested, and 29% transformed from indolent disease. A total of 106, 78, 36, and 22 patients received bendamustine, gemcitabine, lenalidomide, and ibrutinib, respectively. For all patients, median EFS was 5.1 months and median OS was 14.3 months in 2L. Median EFS was 7.6, 2.4, 9.1, and 4.2 months, and median OS was 16.0, 9.4, 16.3, and 11 months for bendamustine, gemcitabine, lenalidomide, and ibrutinib in 2L, respectively. Patients receiving bendamustine and lenalidomide demonstrated significantly improved EFS compared to those receiving gemcitabine (p=0.001 and 0.01, respectively), see Figure 1. We observed no difference in EFS (p=0.40) or OS (p=0.89) between lenalidomide and bendamustine in 2L. Univariate analysis demonstrated receipt of gemcitabine, ECOG PS>1, and IPI >2 to have statistically significant increased hazard for treatment failure and ECOG PS>1 to have an increased hazard for death in 2L relative to the reference group. Multivariate analysis demonstrated receipt of gemcitabine (HR 1.57, p=0.03 95% CI: 1.04 - 2.37) and ECOG PS>1 (HR 1.61, p=0.02 95% CI: 1.09-2.38) were associated with an increased hazard for treatment failure in 2L. Median EFS for patients on lenalidomide was 6.7 and 8 months (p=0.26), and median OS was 13.9 and 12.2 months (p =0.48) for patients with nonGCB and GCB cell of origin, respectively. Conclusions: For patients with R/R DLBCL treated with palliative therapy in the 2L, bendamustine- and lenalidomide-based therapies resulted in significantly longer EFS compared to gemcitabine therapy. Although we cannot exclude the possibility that some patients received gemcitabine in 2L with the original intent to proceed with autoSCT, this does not contest our results as this therapy remains inferior to bendamustine and lenalidomide even if given to a potentially more fit patient population. Analysis shows no difference in outcomes by cell of origin if receiving lenalidomide in 2L. These findings may serve as benchmarks for outcomes following receipt of these therapies in the non-investigational setting and suggest both bendamustine and lenalidomide may be considered reasonable standard-of-care therapies for patients unfit for autoSCT in the 2L setting. Figure 1 Disclosures Landsburg: Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Triphase: Research Funding; Takeda: Research Funding; Takeda: Research Funding. OffLabel Disclosure: Outcomes with lenalidomide and ibrutinib in patients with relapsed/refractory DLBCL will be discussed.

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EARLY Results of TOTAL Therapy 7 (TT7): High Response Rates of NEWLY Diagnosed High Risk Myeloma to Daratumumab

Blood ◽

10.1182/blood-2019-131887 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4569-4569 ◽

Cited By ~ 1

Author(s):

Frits van Rhee ◽

Sharmilan Thanendrarajan ◽

Carolina D. Schinke ◽

Jeffery R. Sawyer ◽

Adam Rosenthal ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Response Rates ◽

Newly Diagnosed ◽

Advisory Committees ◽

Early Results ◽

Research Grant

Background. The TT approach has significantly improved the outcome of multiple myeloma (MM) by combining new drugs with a regimen that comprises induction, tandem autologous stem cell transplantation (ASCT), consolidation and maintenance. However, a group of 15% of patients with high risk multiple myeloma (HRMM) have derived little benefit despite similar response rates to induction chemotherapy and ASCT when compared to low risk MM. The poor outcome of HRMM is explained by early relapse post ASCT resulting in a short progression free survival (PFS) with only 15-20% of patients surviving long-term. Daratumumab (Dara) is a human IgG1k anti-CD38 monoclonal antibody that has shown favorable results in early single-arm studies and more recently in phase III studies for relapsed/refractory and newly diagnosed MM. In TT7, we introduced Dara during all phases of therapy, including immune consolidation early post ASCT, to improve responses rate and PFS in HRMM. Methods. Patients had newly diagnosed HRMM as defined by high risk cytogenetic abnormalities, presence of extramedullary disease, >3 focal lesions on CT-PET, elevated LDH due to MM, or ISS II/III with cytogenetic abnormality. Dara (16mg/kgx1) was added to induction with KTD-PACE (carfilzomib, thalidomide, dexamethasone; and four-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, etoposide). Conditioning for tandem autologous stem cell transplantation (ASCT) was with fractionated melphalan (50mg/m2x4) (fMEL) based on prior observations that patients with adverse cytogenetics fare better with fMEL rather than single high dose MEL200mg/m2.In the inter tandem ASCT period immunological consolidation with Dara (16mg/kg) alone for 2 doses was followed by Dara (16mg/kg) on day 1 combined with K (36mg/m2) and D (20mg) weekly for 2 cycles. DaraKD was administered to avoid treatment free periods allowing for myeloma regrowth. The 2nd ASCT was followed by further immunological consolidation with Dara (16mg/k) for 2 doses, and maintenance therapy for 3 yrs with 3-months block of alternating Dara-KD (dara 16mg/kg day 1; K 36mg/m2 and dex 20mg weekly) and Dara-lenalidomide (R)D (dara 16mg/kg day 1; R 15mg day 1-21 q28 and D 20mg weekly). Results. TT7 enrolled 43 patients thus far. The median follow-up was 11 months (range: 1-22). The median age was 61 yrs (range 44-73). Sixteen patients were ≥65 yrs (37.2%). A mean of 29.4x106 CD34+ cells/kg (range: 4.6-86.4) were collected. 36 patients completed ASCT #1 (83.7%) and 18 (41.9%) ASCT #2, whilst 14 patients have proceeded to the maintenance phase. R-ISS II/III or metaphase cytogenetic abnormalities were present in 85.1 and 58.1% of patients, respectively. Elevated LDH or >3FL on CT-PET were noted in 30 and 41.8%. The 1-yr cumulative incidence estimates for reaching VGPR and PR were 87 and 83%, respectively. A CR or sCR was achieved in 68 and 46%. The 1-yr estimates of PFS and OS were 91.6 and 87.2%. 40 subjects are alive, whilst 5 progressed on study therapy and 3 subsequently died. 38 patients are progression free at the time of reporting. Dara was well-tolerated and no subjects discontinued therapy due to dara-related side effects. The CR and sCR rates compared favorably to the predecessor HRMM TT5 protocol where CR and sCR rates were 59 and 27%. Conclusion. The early results of TT7 point to increased response rates of HRMM to a dara-based TT regimen with especially higher rates of CR and sCR. Longer follow-up is required to determine if these early results translate into superior PFS and OS. Figure Disclosures van Rhee: Karyopharm Therapeutics: Consultancy; Kite Pharma: Consultancy; Adicet Bio: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy; Castleman Disease Collaborative Network: Consultancy; EUSA: Consultancy. Walker:Celgene: Research Funding. Morgan:Amgen, Roche, Abbvie, Takeda, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: research grant, Research Funding. Davies:Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor; Janssen, Celgene: Other: Research Grant, Research Funding.

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Maintenance and Consolidation Regimens after a Second Autologous Transplant for Multiple Myeloma: A Decade of Experiences

Blood ◽

10.1182/blood-2019-130619 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5700-5700

Author(s):

Ghulam Rehman Mohyuddin ◽

Maire Okoniewski ◽

Osama Diab ◽

Siddhartha Ganguly ◽

Al-Ola Abdallah ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Median Time ◽

Research Funding ◽

Standard Of Care ◽

Advisory Board ◽

Advisory Committees ◽

Fda Approval ◽

Novel Drugs ◽

Significant Difference

Introduction: Autologous stem cell transplant (ASCT) followed by maintenance is the standard of care for eligible patients with multiple myeloma (MM). For patients that relapse, a second ASCT remains a viable option. However, the maintenance regimen to use for such patients remains an unanswered question, particularly in those with prior lenalidomide exposure. We retrospectively analyzed patients receiving two autologous transplants for a diagnosis of MM at our institution from 2008 to 2018 to determine maintenance strategies and outcomes upon completion of a second transplant. Methods: A total of 189 patients received two or more autologous transplants for MM at our institution from 2008 to 2018. Patients with planned tandem transplants, or those that proceeded directly to another transplant without interval progression were excluded. The remaining 135 patients were analyzed. Results: Patient characteristics are shown in Table 1. After first ASCT, 94 out of 135 patients (69.6 %) started maintenance therapy. The most commonly used maintenance regimen was lenalidomide in 63 patients, followed by bortezomib in 12 patients and thalidomide in 10 patients. Median time to initiation of maintenance from the date of transplant was 3.9 months. Overall median progression free survival (PFS) from transplant was 24.7 months with no significant difference between groups that received lenalidomide (median PFS: 21.2 months) or bortezomib (median PFS: 19.2 months, p:0.12). 10 (15.8%) patients discontinued lenalidomide due to toxicity, and 1 patient (8.3%) discontinued bortezomib due to toxicity. The median time from the onset of disease progression post first ASCT to time of second ASCT was 5.8 months. Strategies used post second ASCT includedconsolidation with triplet regimens followed by de-escalation (n=11) versus monotherapy (n=100). Table 2 highlights differing maintenance regimens used after the second ASCT. Median time from second ASCT to initiation of maintenance was 4.0 months. Median PFS post ASCT was 20.7 months. There was no statistically significant difference in PFS between the different regimens used (p=0.26), although there was a numerically higher discontinuation rate due to toxicity with older agents such as lenalidomide and bortezomib compared with newer agents such as daratumumab and pomalidomide. There was no statistically significant difference in the cytogenetic risk profile (p=0.21) or stage at diagnosis (p=0.36) between the groups that received different types of maintenance agents. However, patients receiving daratumumab as maintenance were more likely to have received more lines of therapy (median 5 for Daratumumab vs 3 for Lenalidomide, p=0.0001), and more likely to have previous exposure to daratumumab prior to second ASCT (92% vs 0% for other agents p=0.0001). Patients receiving daratumumab, carfilzomib or triple therapy were more likely to have been refractory to both a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) (p=0.0001). Despite stratifying for use of newer novel drugs (FDA approval after 2010- pomalidomide, daratumumab, carfilzomib) vs older novel drugs (FDA approval before 2010- lenalidomide, bortezomib, thalidomide), there was no difference in PFS ( 21.2 months vs 20.4 months, p= 0.92), between these groups when used as part of a maintenance strategy. Conclusions: Our data show a variety of maintenance and consolidation regimens are used for patients with MM after their second ASCT. In this single-center, retrospective analysis, there was no clear superiority of a consolidative strategy using triplet over monotherapy, and no superiority of newer agents compared to older agents. This suggests that toxicity, prior therapies and their tolerance may be the more important patient-related factors for consideration when selecting an agent/agents. Randomized, prospective data will be important to ascertain the standard of care in this situation. Disclosures Ganguly: Daiichi Sankyo: Research Funding; Seattle Genetics: Speakers Bureau; Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board. McGuirk:Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bellicum Pharmaceuticals: Research Funding; Astellas: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation.

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