scholarly journals Rapid and Deep Hematologic Responses Are Associated with Improved Major Organ Deterioration Progression-Free Survival in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Ashutosh D. Wechalekar ◽  
Giovanni Palladini ◽  
Giampaolo Merlini ◽  
Raymond L. Comenzo ◽  
Arnaud Jaccard ◽  
...  
Keyword(s):  
Research Funding ◽  
Progression Free Survival ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Free Survival ◽  
Major Organ ◽  
End Stage

Background: As immunoglobulin light chains present in AL amyloidosis are considered to be toxic to involved organs, especially the heart, rapid and deep hematologic remission with reduction of these light chains with frontline therapy may be crucial to improving long-term clinical outcomes. ANDROMEDA (NCT03201965) is the first phase 3 study in this patient population to evaluate major organ deterioration progression-free survival (MOD-PFS), a composite endpoint of time to end-stage cardiac disease (requiring cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); end-stage renal disease (requiring hemodialysis or renal transplant); hematologic progression per consensus guidelines1; and death. Here, we report the impact of early and deep hematologic responses on MOD-PFS. Methods: ANDROMEDA is a randomized, open-label, active-controlled phase 3 study of patients with newly diagnosed AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (VCd) ± daratumumab subcutaneous (DARA SC; DARA 1800 mg coformulated with recombinant human hyaluronidase PH20 in 15 mL). Key eligibility criteria were newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage I-IIIA, eGFR ≥20 mL/min, and absence of symptomatic multiple myeloma. Disease evaluations occurred every 4 weeks during Cycles 1-6. Hematologic responses were adjudicated by an Independent Review Committee. Landmark analyses for response were performed at 1 and 3 months (± 7 days). Analyses of hematologic responses and MOD-PFS were performed on the intent-to-treat analysis set. Patients without a baseline or post-baseline assessment were censored at randomization for the MOD-PFS analysis. Hazard ratios and corresponding 95% confidence intervals were estimated based on Cox proportional hazard model. Results: A total of 388 patients were randomized to DARA-VCd (n=195) or VCd alone (n=193). Baseline characteristics were well balanced between groups. The proportions of patients with heart and kidney involvement were 71% and 59%, respectively. Median follow-up was 11.4 months (range, 0.03-21.3+). For the 1- and 3-month landmark analysis, hematologic response was available for 356 and 289 patients, respectively. Hematologic response rates by treatment group at 1 and 3 months are shown in the Table. MOD-PFS was longer in patients with complete response (CR)/very good partial response (VGPR) at 1 and 3 months vs patients with lower levels of response (Figure). CR/VGPR at 1 and 3 months was associated with reduced risk of death or major organ deterioration in a multivariate analysis adjusting for baseline difference between involved and uninvolved free light chains and cardiac stage, (HR: 0.399, P=0.0006 and HR: 0.262, P=0.0003, respectively). At 1 and 3 months, cardiac and renal response rates were higher in those who achieved early and deep hematologic responses (CR and VGPR). Conclusions: CR/VGPR at 1 and 3 months was associated with a reduced risk of major organ deterioration and death in patients with newly diagnosed AL amyloidosis. These data confirm that initial therapy that achieves rapid and deep hematological responses is essential to improving long-term outcomes in AL amyloidosis. Reference 1. Comenzo RL, et al. Leukemia. 2012;26(11):2317-25 Disclosures Wechalekar: Janssen: Honoraria, Other: Advisory; Caelum: Other: Advisory; Celgene: Honoraria; Takeda: Honoraria, Other: Travel. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other. Comenzo:Caleum: Consultancy; Unum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Jaccard:Celgene: Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Celgene., Research Funding; Janssen: Consultancy, Honoraria, Other: A.J. has served in a consulting or advisory role for Janssen and has received honoraria from, received research funding from, and had travel, accommodations, or other expenses paid for or reimbursed by Janssen., Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Pei:Janssen: Current Employment, Current equity holder in publicly-traded company. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Kastritis:Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

scholarly journals Subcutaneous Daratumumab (DARA SC) + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Asian Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: Subgroup Analysis from the Phase 3 Andromeda Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Kenshi Suzuki ◽  
Ashutosh D. Wechalekar ◽  
Kihyun Kim ◽  
Chihiro Shimazaki ◽  
Jin Seok Kim ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Research Funding ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Duration Of Treatment ◽  
Phase 3 ◽  
Asian Patients ◽  
Kidney Involvement ◽  
Major Organ

Introduction: Systemic AL amyloidosis is a rare disorder of clonal CD38+ plasma cells characterized by deposition of insoluble amyloid fibrils leading to tissue damage and organ dysfunction. Currently, there are no health authority-approved treatments for AL amyloidosis, and standard of care (SoC) includes therapies developed for multiple myeloma (MM). DARA is a human CD38-targeting antibody for MM. Combining DARA with VCd improved outcomes for AL amyloidosis versus VCd alone in the phase 3 ANDROMEDA study. Here, we report a subgroup analysis of Asian patients (China, Japan, and Korea) from ANDROMEDA. Methods: Eligible patients had newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, cardiac stage (Mayo 2004) I-IIIA, eGFR ≥20 mL/min, and no symptomatic MM. Patients were randomized 1:1 to receive DARA SC plus VCd (D-VCd) or VCd. All patients received bortezomib (1.3 mg/m2 SC QW), cyclophosphamide (300 mg/m2 PO or IV QW), and dexamethasone (40 mg PO or IV QW) for six 28-day cycles with or without DARA SC (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20]; ENHANZE® drug delivery technology, Halozyme, Inc.) by injection QW in Cycles 1-2, Q2W in Cycles 3-6; after Cycle 6, patients continued DARA monotherapy as maintenance for up to 24 cycles (28-day cycles). Disease status was evaluated Q4W in Cycles 1-6 and Q8W after Cycle 7 until hematologic progression or major organ deterioration. The primary endpoint was overall hematologic complete response (CR) rate; key secondary endpoints included major organ deterioration progression-free survival (MOD-PFS), survival, and safety. MOD-PFS was defined as the time from randomization to any of the following events (whichever occurred first): death, clinical manifestation of cardiac or renal failure, or hematologic progression. Results: Among 388 randomized patients (D-VCd, n=195; VCd, n=193), 60 were Asian (D-VCd, n=29; VCd, n=31). Baseline characteristics were well balanced between arms and consistent with the intent-to-treat population. The median age was 66 years, 70% and 58% had heart and kidney involvement, respectively, and 60% had ≥2 organs involved. Cardiac stage I, II and IIIA/B were 28%, 28%, and 43%, respectively. The median duration of treatment was 9.2 mo for D-VCd and 5.3 mo for VCd. Median follow-up was 9.4 mo. The overall hematologic CR rate was 59% for D-VCd and 10% for VCd (odds ratio, 13.2; 95% CI, 3.3-53.7; P<0.0001). D-VCd vs VCd achieved higher rates of very good partial response or better (≥VGPR; 93% vs 61%). MOD-PFS favored D-VCd-treated patients (HR 0.21; 95% CI, 0.06-0.75, P=0.0079). A total of 12 deaths occurred (D-VCd, n=3; VCd, n=9). The most common (≥10%) grade 3/4 TEAEs were lymphopenia (D-VCd 35%/VCd 32%), neutropenia (10%/3%), diarrhea (10%/7%), pneumonia (7%/10%), cardiac failure (7%/10%), hypokalemia (7%/10%), anemia (3%/10%), thrombocytopenia (3%/10%), hypoalbuminemia (3%/10%), and syncope (3%/10%). TEAEs leading to treatment discontinuation occurred in 1 patient in each treatment arm. Conclusion: The addition of DARA SC to VCd was superior to VCd alone in Asian patients, resulting in deeper hematologic responses and improved clinical outcomes, including MOD-PFS, with a safety profile consistent with the overall study population. These data support the use of D-VCd in Asian patients with newly diagnosed AL amyloidosis. Disclosures Suzuki: Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Takeda, Amgen, Janssen and Celgene: Consultancy; Bristol-Myers Squibb, Celgene and Amgen: Research Funding. Wechalekar:Janssen, Takeda, Caelum, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:BMS, Takeda, Amgen, Celgene, Janssen: Consultancy, Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Zhou:Peking University First Hospital: Current Employment. Iida:Celgene: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Chugai: Research Funding; Kyowa Kirin: Research Funding; AbbVie: Research Funding; Merck Sharpe Dohme: Research Funding; Janssen: Honoraria, Research Funding. Tran:Janssen: Current Employment, Current equity holder in publicly-traded company. Qin:Janssen: Current Employment. Vasey:Janssen Research & Development: Current Employment, Current equity holder in publicly-traded company. Tromp:Janssen: Current Employment, Current equity holder in publicly-traded company. Weiss:Janssen: Current Employment, Current equity holder in publicly-traded company. Vermeulen:Janssen: Current Employment, Current equity holder in publicly-traded company. Comenzo:Amgen: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Caleum: Consultancy; Karyopharm: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel/accommodations/expenses; Janssen: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding; Pfizer: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel/accommodations/expenses. OffLabel Disclosure: To evaluate the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with AL amyloidosis.

scholarly journals Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes

2015 ◽  
Vol 122 (4) ◽  
pp. 825-832 ◽  
Author(s):  
Robert J. Weil ◽  
Gaurav G. Mavinkurve ◽  
Samuel T. Chao ◽  
Michael A. Vogelbaum ◽  
John H. Suh ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Intraoperative Radiotherapy ◽  
Progression Free Survival ◽  
Patient Treatment ◽  
Karnofsky Performance Scale ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Solitary Brain Metastasis ◽  
Free Survival

OBJECT The authors assessed the feasibility of intraoperative radiotherapy (IORT) using a portable radiation source to treat newly diagnosed, surgically resected, solitary brain metastasis (BrM). METHODS In a nonrandomized prospective study, 23 patients with histologically confirmed BrM were treated with an Intrabeam device that delivered 14 Gy to a 2-mm depth to the resection cavity during surgery. RESULTS In a 5-year minimum follow-up period, progression-free survival from the time of surgery with simultaneous IORT averaged (± SD) 22 ± 33 months (range 1–96 months), with survival from the time of BrM treatment with surgery+IORT of 30 ± 32 months (range 1–96 months) and overall survival from the time of first cancer diagnosis of 71 ± 64 months (range 4–197 months). For the Graded Prognostic Assessment (GPA), patients with a score of 1.5–2.0 (n = 12) had an average posttreatment survival of 21 ± 26 months (range 1–96 months), those with a score of 2.5–3.0 (n = 7) had an average posttreatment survival of 52 ± 40 months (range 5–94 months), and those with a score of 3.5–4.0 (n = 4) had an average posttreatment survival of 17 ± 12 months (range 4–28 months). A BrM at the treatment site recurred in 7 patients 9 ± 6 months posttreatment, and 5 patients had new but distant BrM 17 ± 3 months after surgery+IORT. Six patients later received whole-brain radiation therapy, 7 patients received radiosurgery, and 2 patients received both treatments. The median Karnofsky Performance Scale scores before and 1 and 3 months after surgery were 80, 90, and 90, respectively; at the time of this writing, 3 patients remain alive with a CNS progression-free survival of > 90 months without additional BrM treatment. CONCLUSIONS The results of this study demonstrate the feasibility of resection combined with IORT at a dose of 14 Gy to a 2-mm peripheral margin to treat a solitary BrM. Local control, distant control, and long-term survival were comparable to those of other commonly used modalities. Surgery combined with IORT seems to be a potential adjunct to patient treatment for CNS involvement by systemic cancer.

Long-Term Efficacy and Safety (27 months) of the Biosimilar CT-P10 in Patients with Low Tumor Burden Follicular Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Larry W Kwak ◽  
Juan Manuel Sancho ◽  
Seok-Goo Cho ◽  
Hideyuki Nakazawa ◽  
Junji Suzumiya ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
Time To Progression ◽  
Advisory Committees ◽  
Free Survival ◽  
Travel Costs ◽  
Single Transition ◽  
Second Year

We assessed long-term safety and efficacy of CT-P10 and rituximab in patients with newly diagnosed low-tumour-burden follicular lymphoma (LTBFL), and following a single transition from rituximab to CT-P10. This double-blind, parallel-group, active-controlled phase 3 trial randomized patients with CD20+ LTBFL to receive CT-P10 or US-sourced rituximab (375 mg/m2 intravenous). Induction therapy (weekly for 4 cycles) was followed by a 2-year maintenance period for patients achieving disease control (CR, CRu, PR and SD). During the maintenance, CT-P10 or rituximab were administered every 8 weeks (6 cycles) in the first year and additional CT-P10 was administered every 8 weeks (6 cycles) in the second year. Secondary endpoints (reported here) were overall response rate during the study period, progression-free survival, time-to-progression, and overall survival. Safety and immunogenicity were also evaluated over the study period. Between Nov 9, 2015 and Jan 4, 2018, 258 patients were randomised (130 CT-P10; 128 rituximab). Over the study period, 115 (88%; CT-P10) and 111 (87%; rituximab) patients achieved overall response. At a median follow-up of 29·2 months (IQR: 26·1-33·7), median progression-free survival, time-to-progression, and overall survival were not estimable. The KM estimates (95% CI) for OS at 36 months were 98% (93-99) and 97% (89-99) in the CT-P10 and rituximab groups, respectively. Corresponding values for PFS were 80% (70-87) and 68% (54-79), while results for TTP were 82% (72-88) and 68% (54-79) in the CT-P10 and rituximab groups, respectively. (Figure A. OS; Figure B. PFS and Figure C. TTP) Over the study period, 114 (88%) and 104 (81%) patients in the CT-P10 and rituximab groups, respectively, experienced at least one treatment-emergent adverse event (TEAE) and 14 (11%) patients in each group experienced TE-serious adverse events (TESAEs). There were no unexpected safety findings observed during the second year of the maintenance period after single transition from rituximab to CT-P10. Figure 1 Disclosures Kwak: Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Xeme Biopharma/Theratest: Other: equity; CJ Healthcare: Consultancy; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. Sancho:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gelgene: 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; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Menne:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Other: Travel costs, Speakers Bureau; Pfizer: Honoraria, Other: Travel costs, Speakers Bureau; Celgene: Honoraria, Other: Travel grants; Roche: Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Research Funding; Takeda: Honoraria, Speakers Bureau. Jurczak:Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Acerta: Research Funding; Bayer: Research Funding; Janssen: Research Funding; MeiPharma: Research Funding; Pharmacyclics: Research Funding; Roche: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Trneny:Gilead: Consultancy, Honoraria, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Celgene: Consultancy; Incyte: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses. Ogura:Cellgene: Honoraria; Chugai: Honoraria; Denovo Biopharma: Membership on an entity's Board of Directors or advisory committees; MejiSeika Pharma: Membership on an entity's Board of Directors or advisory committees; Mundi Pharma: Membership on an entity's Board of Directors or advisory committees; SymBio: Membership on an entity's Board of Directors or advisory committees; TevaTakeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Membership on an entity's Board of Directors or advisory committees. Kim:Pfizer: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; F. Hoffmann-La Roche: Research Funding; Kyowa Kirn: Research Funding; Celltrion: Research Funding; JJ: Research Funding. Lee:Celltrion, Inc.: Current Employment. Kim:Celltrion, Inc.: Current Employment. Ahn:Celltrion, Inc.: Current Employment. Buske:Roche, Janssen, Bayer, MSD: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, AbbVie, Pfizer, Celltrion: Honoraria, Speakers Bureau. OffLabel Disclosure: Rituximab monotherapy to LTBFL patients

scholarly journals An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Stem Cell Transplantation for Frontline, Stage III or IV Classical Hodgkin Lymphoma Based on the 5-Year Update of the ECHELON-1 Trial: A United States Perspective

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2440-2440
Author(s):  
Tycel Phillips ◽  
Kristen Migliaccio-Walle ◽  
Kristina S. Yu ◽  
Brian Bloudek ◽  
Nicholas Liu ◽  
...  
Keyword(s):  
Simulation Model ◽  
Research Funding ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Publicly Traded ◽  
Free Survival ◽  
Annual Prevalence ◽  
Number Of Patients ◽  
Relapsed Disease

Abstract Objectives Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is the most common frontline (1L) regimen for patients with stage III or IV classical Hodgkin lymphoma (cHL), but about 30% of patients with stage III or IV cHL have refractory or relapsed disease after ABVD treatment. Based on the 5-year update of the ECHELON-1 trial, patients on 1L brentuximab vedotin, doxorubicin, vinblastine and dacarbazine (A+AVD) continued to demonstrate a robust and durable progression-free survival (PFS) improvement vs ABVD with a 32% reduction in the risk of progression or death (HR=0.681, nominal P=0.002). Our objective was to estimate the future number of patients with cHL who are alive and progression-free over 10-years with 1L A+AVD, based on the 5-year follow-up results from ECHELON-1. Methods An oncology simulation model, from the United States perspective, was developed with a 1-month cycle length that estimates population-level outcomes based on annual prevalence of cHL, considering disease incidence, treatment patterns, PFS, and overall survival of commonly used treatment regimens for stage III or IV cHL. Incidence of cHL was derived from the 2019 Surveillance, Epidemiology, and End Results (SEER) Program, assuming 95% of HL is classical of which 41% is stage III or IV. To populate the base case model, treatment patterns following 1L use of ABVD (64.5%) and positron emission tomography (PET)-adapted therapy (35.5%) were varied over time and compared to A+AVD (24%). For every model cycle, patients who experienced disease progression on 1L therapy discontinued therapy and transitioned to second-line (salvage) therapy. The transition from second-line therapy to transplant is also included in the model based on patient eligibility. Model inputs were informed by 1) real-world treatment utilization; 2) treatment-specific clinical trial data, including ECHELON-1 with 5-year PFS rates of 75.3% for ABVD (95% CI: 70.0, 85.0) and 82.2% for A+AVD (95% CI: 71.7, 78.5); and 3) expert clinicians' opinions. Annual prevalence of patients living progression-free with cHL in the 1L setting with each prescribing scenario was estimated for 10 years (year 2031) with and without the availability of A+AVD. Results The annual number of newly diagnosed patients with stage III or IV cHL at 10 years in 2031 was estimated at 3,586. The number of patients alive and progression-free in the 1L setting was 19,494 without A+AVD and 19,660 with A+AVD (Δ+166, 0.85% increase) in 2031. Overall, for every 100 patients prescribed A+AVD, it was predicted that an additional 6.5 patients per year achieved at least 5 years PFS and 4.2 to 4.7 fewer patients per year required a stem cell transplant (SCT), based on the 70% to 80% of eligible patient proceeding to SCT, respectively. Conclusions The durable PFS improvement of A+AVD vs ABVD in the 5-year follow-up data from ECHELON-1 resulted in increasing the number of patients with stage III or IV cHL who remain progression free for greater than 10 years and reducing future SCTs, based on this oncology simulation model for cHL. The significant improvement in PFS observed in the 5-year ECHELON-1 trial may translate to fewer patients with cHL developing primary refractory or relapsed disease and reduce the need for additional therapies including SCT. Disclosures Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy. Migliaccio-Walle: Seagen, Inc: Consultancy. Yu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Bloudek: Seagen, Inc: Consultancy. Liu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Burke: Beigene: Consultancy, Speakers Bureau; Verastem: Consultancy; Kymera: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive Biotechnologies: Consultancy; MorphoSys: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy; Kura: Consultancy; Epizyme: Consultancy; X4 Pharmaceuticals: Consultancy; SeaGen: Consultancy, Speakers Bureau; AbbVie: Consultancy.

scholarly journals Optimal Therapy for Relapsed AL Amyloidosis Post Autologous Stem Cell Transplant

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3171-3171
Author(s):  
M Hasib Sidiqi ◽  
Abdullah S. S. Al Saleh ◽  
Iuliana Vaxman ◽  
Angela Dispenzieri ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Survival ◽  
Treatment Regimens ◽  
2Nd Generation

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

Allogeneic Stem Cell Transplantation (SCT) for Multiple Myeloma (MM) - What Has Changed? : A CIBMTR Analysis From 1989 – 2005.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 54-54 ◽  
Author(s):  
Shaji Kumar ◽  
Smriti Shrestha ◽  
Mei-Jie Zhang ◽  
Angela Dispenzieri ◽  
Gustavo A. Milone ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
The Past ◽  
Over Time

Abstract Abstract 54 Despite its curative potential, the role of allogeneic stem cell transplant (allo-SCT) in MM has been limited by high treatment related mortality (TRM). Autologous stem cell transplant (auto-SCT) thus remains the standard of care for eligible patients (pts) with MM. Recently interest in allo-SCT has been increasing due to the incurable nature of MM, better risk stratification models, improved supportive care and finally the increasing experience with less toxic reduced intensity conditioning. We analyzed the trends in practice of allo-SCT for MM over the past two decades. A total of 1211 pts undergoing allo-SCT for MM between 1989 and 2005, reported to the CIBMTR were analyzed in three cohorts based on year of allo-SCT: 1989–1994 (n=346), 1995–2000 (n=285), and 2001–2005 (n=580). Probabilities of progression-free survival (PFS) and overall survival (OS) and cumulative incidence estimates of TRM and relapse were calculated. Patient characteristics are summarized in table 1. Patients transplanted in the later cohort (2001–2005) were of higher age with 53% above age 50 years (vs. 12% in 1989–1994). There was decreasing use of myeloablative regimens and bone marrow grafts over time (82% vs. 62% vs. 9% for myeloablative regimens and 99%, 62% and 13% for marrow grafts respectively). Increasing number of pts in the later cohort received an auto-SCT prior to allo-SCT (Table 1). The proportion of unrelated allo-SCTs increased over time (5% vs. 21% vs. 33%). Graft versus host (GVH) prophylaxis changed over time with increasing use of cyclosporine with agents other than methotrexate and increasing use of ATG in the recent years. Median survival increased over the three time periods from 1989 – 2005: 11.1 months (mos.) vs. 12.2 mos vs. 20.3 mos. The 100 day mortality decreased steadily over successive time periods; 35% (95% CI; 29–31), 29% (24–35) and 19% (16–23) respectively. Similarly, the TRM at 5 years remained steady between the first two periods, but decreased in the last period (40 & 48% vs. 29%). The incidence of chronic GVHD increased in the later cohort but the incidence of acute GVHD was similar over the years. While PFS was the lowest for the most recent group (15% at 5 years), the overall survival at 5 years was similar among the groups (30, 32, and 29 mos). Long term PFS at 10 years was 18% in the 1989–1994 cohort and 17% in 1995–2000. Long term OS at 10 years was 23% in 1989 – 1994 and 1995–2000 cohorts. Results are summarized in table 1. A clear trend towards reduced intensity conditioning, unrelated donor SCT, use of PBSC grafts and selection of older patients was noted. There was increasing use of tandem auto-allo SCT with an increasing proportion of patients with a prior auto-SCT. While the TRM has decreased significantly in the last cohort, this did not translate into an improvement in survival primarily because of increased risk of relapse in the latter cohort. Long term (>10yr) progression free survival which may approach a cure has remained unchanged over the past two decades at <20%. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

Disease-Management of Low- and Intermediate-1 Risk Myelodysplastic Syndromes: Report on 800 Newly Diagnosed MDS Patients From the European LeukemiaNet MDS Registry

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2917-2917 ◽  
Author(s):  
Louise de Swart ◽  
Alex Smith ◽  
Pierre Fenaux ◽  
Argyris Symeonidis ◽  
Eva Hellström-Lindberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Management ◽  
Serum Ferritin ◽  
Research Funding ◽  
Iron Chelation ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
The Mean

Abstract Abstract 2917 Background: The European LeukemiaNet MDS (EUMDS) registry is designed to collect information about the demographics and disease-management of newly diagnosed low-risk and intermediate-1 risk MDS patients. From April 2008 until July 2010, 828 patients have been registered in eleven participating countries through a web-based reporting system. Objectives: This report describes the disease-management of the first 800 registered patients, including transfusion-related issues like secondary iron overload and its treatment. Results: 159 of 800 patients (20%) started MDS specific treatment within three months before registration; this percentage increased to 50% at 18 months of follow-up. Most patients received erythroid-stimulating agents (ESA), like erythropoietin (Table 1). In patients with a clinical indication for ESA, the percentage of transfusion-independency was similar to the transfusion-independent group without indication for ESA at 18 months of follow-up (Table 1). Overall, 27% of the patients received blood transfusions at registration. This percentage remained stable during follow-up, probably due to the therapeutic effect of ESA (Table 1). The number of units transfused, per 6 months, in these patients increased from 5 to 13 units at 18 months of follow-up, with a mean pre-transfusion Hb level of 7.6 g/dL. The serum ferritin levels of the transfusion-dependent patients at registration were available in 159 patients. The serum ferritin level at registration was ≥2000 μg/L in 4% of the patients who received a mean number of 10 units (SD 7). This increased to 28% of the patients who received a mean number of 20 units (SD 11) at 18 months of follow-up. The percentage of patients on iron chelation therapy increased from 1% to 9% during follow-up (Table 1). In these patients the mean serum ferritin levels remained stable: 1913 μg/L (SD 1183) at registration and 1626 μg/L (SD 1232) at 18 months of follow-up. In contrast, transfusion-dependent patients not treated with iron chelation or ESA had increasing ferritin levels, with a mean ferritin of 630 μg/L (SD 597) at registration and 1586 μg/L (SD 1017) at 18 months of follow-up. 37 patients (5%) progressed to high-risk MDS or acute myeloblastic leukemia at a median of 155 days from registration. 62 patients (8%) have died within a median of 269 days from registration, 32 deaths were MDS related. The overall survival was 93% at 18 months of follow-up, with a progression-free survival of 90%. Differences in overall survival between transfusion-independent and transfusion-dependent patients were significant: 97% versus 85%, respectively (p<0.0001; Table 2). In the multivariate analysis transfusion-dependency, ferritin levels and IPSS score predicted survival (Table 2). The IPSS score had a significant prognostic impact on overall survival and progression-free survival in contrast to the WHO classification (Data not shown). Conclusions: Despite a high transfusion load the mean serum ferritin levels remained stable during treatment with iron chelation. Transfusion-dependent patients had a worse overall survival and progression-free survival with higher ferritin levels and higher IPSS score as compared to transfusion-independent patients. This report demonstrates the importance of detailed disease-management in low- and intermediate-1 risk MDS patients. Disclosures: Fenaux: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding. Bowen:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AMGEN: Honoraria; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.

Significance of ELN Provisional Response Definitions In Predicting Long-Term Outcomes of Patients with CP-CML Treated with Dasatinib After Imatinib Failure.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3439-3439
Author(s):  
Jorge E. Cortes ◽  
Neil P. Shah ◽  
Charles A. Schiffer ◽  
Philipp D. LeCoutre ◽  
Giuseppe Saglio ◽  
...  
Keyword(s):  
Research Funding ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Optimal Response ◽  
Response Table ◽  
Starting Dose

Abstract Abstract 3439 Introduction: The European LeukemiaNet (ELN) recommendations for the management of chronic phase chronic myeloid leukemia (CP-CML) have provisionally defined criteria for suboptimal and failure to second-generation tyrosine kinase inhibitors (TKIs) (Baccarani et al., J Clin Oncol. 27 (35):6041-51, 2009). We tested the significance of these definitions in 3 studies of dasatinib after imatinib failure. Methods: Data from 1150 treated patients (pts) included in the 3 studies [CA180-013 (n=387); dasatinib only arm of CA180-017 (n=101); CA180-034 (n=662)] were analyzed. For the purpose of this analysis, we modified the 2009 ELN recommendations to add an optimal response category as shown in Table 1. Background: The median age of the pts included in this analysis was 56 yrs (range, 18–85) and the median duration of CML in these pts was 58 months (range, 0.9–250.8). Thirty-eight percent of the pts had received imatinib at a dose > 600mg/day and 45% had been on imatinib therapy >3 yrs. Twenty-four percent of pts included in this analysis had demonstrated imatinib-intolerance. Thirty-five percent of pts had mutations before the start of dasatinib therapy (5% had T315l). Results: Rates of optimal response at 3, 6 and 12 months were 51%, 44% and 36%. Rates of suboptimal response at 3, 6 and 12 months were 7%, 16% and 27%. Rates of failure response at 3, 6 and 12 months were 29%, 34% and 37%. Rates of warning response at 3 and 6 months were 12% and 6%. The starting dose of dasatinib did not influence these response rates. The group defined as suboptimal at 12 months (of whom 52% had already achieved CCyR) had a higher probability of achieving CCyR within 2 yr (83%) compared to the groups defined as suboptimal at 6 months (69%) or 3 months (51%). This suboptimal group at 12 months also had a higher 2 yr progression-free survival (PFS) (92%) compared to the suboptimal groups at 6 months (82%) and 3 months (80%). The probability of achieving an MMR within 2 yr was slightly higher in pts defined as optimal at 6 months (80%) vs. those at 3 months (71%). However, the probability of achieving an MMR within 2 yr showed minimal change for the suboptimal (31-35%) or the failure (5%) response groups defined at 3, 6 and 12 months. The pts with a warnings response had a profile that was intermediate between suboptimal and failure response. Table 2 summarizes 2 yr outcomes based on response. Conclusions: These results suggest that the 2009 ELN provisional response definitions may be helpful in predicting long term outcomes in pts receiving second-line dasatinib therapy. In this cohort of pts, optimal responders identified themselves rapidly as did pts with failure. However, the outcome of pts defined as suboptimal at 12 months appeared more favorable than that of pts defined as suboptimal at 3 and 6 months. This, in addition to the higher proportion of pts classified as suboptimal at 12 months, compared to those classified as suboptimal at 3 and 6 months, may suggest that the ELN defined cut-off between optimal vs. suboptimal at 12 months (i.e. MMR) may need to be modified in order to make the prognosis for suboptimal response more consistent across different time points. Pts classified in the warnings category at 3 and 6 months had an outcome intermediate between those with suboptimal and failure response. Disclosures: Cortes: Bristol-Myers Squibb: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Shah:Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Ariad: Consultancy. LeCoutre:Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria. Kantarjian:Novartis Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding. Jabbour:GlaxoSmithKline: Research Funding. Bahceci:Bristol-Myers Squibb: Employment. Chen:Bristol-Myers Squibb: Employment. Lambert:Bristol-Myers Squibb: Employment. Guilhot:Bristol-Myers Squibb: Consultancy; Novartis: Consultancy.

scholarly journals Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy - Final Analysis from the Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1663-1663
Author(s):  
Rose Turner ◽  
Hang Quach ◽  
Noemi Horvath ◽  
Ian H Kerridge ◽  
Flora Yuen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Free Survival ◽  
Depth Of Response

Abstract BACKGROUND Survival rates in multiple myeloma (MM) have significantly improved in recent decades with the advent of high-dose chemotherapy conditioned autologous stem cell transplantation (ASCT) and the availability of novel agents for induction therapy (Kumar SK et al. Blood 2008). Failure to respond to front-line bortezomib-based induction therapy remains a significant clinical challenge in transplant eligible (TE) newly diagnosed multiple myeloma (NDMM), and is associated with poor outcomes with shortened progression free survival (PFS) and overall survival (OS) (Lee SE et al. Ann Hematol. 2014). In combination with immunomodulatory agents (IMiDs), carfilzomib, a second generation proteosome inhibitor, has been shown to be highly effective in the context of MM induction with high rates of negativity for minimal residual disease (MRD) and few dose limiting toxicities (Langren O et al. Leukemia 2019). The ALLG MM17 trial is a multicentre single arm study of carfilzomib-thalidomide-dexamethasone (KTd) in TE NDMM patients refractory or with suboptimal response to bortezomib-based induction therapy, designed to evaluate the efficacy of early response adaption with a switch to an intensive salvage strategy. METHOD Eligible patients included those with TE NDMM, aged 18 years and older, demonstrating sub-optimal response to bortezomib-based induction therapy (failure to achieve a minimal response after 2 cycles, partial response [PR] after 4 cycles, or disease progression within 60 days of completing induction). Salvage therapy consisted of 100mg daily oral thalidomide, with 20 mg of oral dexamethasone and 20mg/56mg of IV carfilzomib on days 1, 2, 8, 9, 15, and 16, with of each 28-day cycle. Following 4 cycles, patients in stringent complete response (sCR) proceeded to melphalan conditioned ASCT whereas those in less than sCR received a further 2 cycles of KTd prior to ASCT. Consolidation therapy consisted of a further 2 cycles of KTd, followed by maintenance 100mg daily thalidomide and 40mg weekly dexamethasone (Td) continuing until progressive disease, unacceptable toxicity, or 12 months of therapy. Primary objectives were to determine the overall response rate (ORR) and safety profile of treatment with KTd salvage therapy, with secondary objectives to determine the maximal depth of response, progression free survival (PFS), and overall survival (OS) achieved with sequential treatment with KTd salvage, ASCT, post-ASCT consolidation, and maintenance Td therapy. Efficacy assessments were performed via serum protein electrophoresis, serum free light chain and bone marrow evaluation. Next generation flow (NGF) cytometry MRD evaluation of bone marrow aspirate was undertaken pre-ASCT, at day 100 post-ASCT, after 2 cycles of consolidation KTd, and following completion of Td using standardized 8-colour EuroFlow platform. RESULTS 50 patients were recruited across 6 Australian sites between September 2016 and April 2018. Overall response rate to KTd salvage was 78% (Credible Interval 95%: 64.4-87.1%), with dual proof of concept criteria met (observed ORR ≥ 50% and posterior probability that the true ORR exceeds 30% is ≥ 0.90). Response rates included 12% sCR, 6% CR, 38% VGPR, and 22% PR. Sixteen patients discontinued treatment (32%) including 10 cases (20%) of progressive disease, and 2 patient deaths without progression. NGF MRD negativity was found to be 32%, 36% and 55% at the pre-ASCT, post-ASCT and post-consolidation time-points. At the cut-off date, estimated median follow-up for disease status was 38.6 months and median PFS and OS had not been reached. At 36 months PFS and OS were 63.9% (95%CI: 49.0 - 75.5%) and 79.9% (95%CI: 65.8 - 88.6%) respectively (Figure 1). KTd was found to be well tolerated with 44% of patients experiencing a grade 3 of higher adverse event (AE). Most common AEs included upper respiratory infection (48%), peripheral neuropathy (36%), musculoskeletal pain (32%), dyspnoea (28%), fatigue or lethargy (28%), and constipation (28%). Significant cardiac toxicity was not observed at this higher dose level of carfilzomib. CONCLUSION Results demonstrate that response-adaptive utilisation of KTd salvage, ASCT, and consolidation therapy induces high response rates, improving depth of response with high levels of sequential MRD negativity, and durable responses with an acceptable toxicity profile in TE NDMM patients failing bortezomib-based induction therapy. Figure 1 Figure 1. Disclosures Quach: Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, 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; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kalff: Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Roche: Honoraria; CSL: Honoraria; Sandoz: Honoraria. Bergin: Amgen: Other: Travel to workshop; Celgene: Consultancy. Reynolds: Novartis AG: Current equity holder in publicly-traded company; Alcon: Current equity holder in publicly-traded company; Abbvie: Research Funding. Spencer: Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria.

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.

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