A phase II study of chemoradiotherapy in patients with stage II, III esophageal squamous cell carcinoma (ESCC): (JCOG 9906)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15137-15137 ◽  
Author(s):  
K. Muro ◽  
A. Ohtsu ◽  
S. Ishikura ◽  
N. Boku ◽  
H. Takiuchi ◽  
...  
Keyword(s):  
Radiation Pneumonitis ◽  
Clinical Stage ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Stage Ii ◽  
Study Objective ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3

15137 Background: The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy (CRT) with cisplatin and 5- fluorouracil (5FU) in patients with stage II, III ESCC. Methods: Patients with clinical stage II or III (T1N1 or T2–3N0–1 and M0) thoracic ESCC, age of 70 or younger, preserved organ functions were eligible. Treatment consisted of two courses of cisplatin 40 mg/m2 (day 1, 8) and 5FU 400 mg/m2/day (days 1–5, 8–12), q5w combined with concurrent radiotherapy of 60 Gy in 30 fractions over 8 weeks with 2-week break. For responders, two courses of chemotherapy of cisplatin 80 mg/m2 (day 1) and 5FU 800 mg/m2/day (days 1–5) q4w were added. The primary endpoint was overall survival and the secondary endpoints were response, toxicity, and progression-free survival. Results: From April 2000 to March 2002, 76 patients were accrued from 12 institutions. Characteristics of all patients were as follows: median age of 61 (range 39–70), male/female; 68/8, PS 0/1; 59/17, stage IIA/IIB/III; 26/12/38. There were two ineligible cases with inadequate liver function and T4 disease. Grade 4 neutropenia, leukopenia, and anemia occurred in 1.3%, 1.3% and 2.6%. Grade 3/4 esophagitis, stomatitis and infection occurred in 17%, 8% and 17%. Grade 3/4 late toxicities occurred in the following incidences; esophagus (dysphagia, mucositis, stenosis, and fistula) in 13%, pericardial effusion in 17%, pleural effusion in 8%, and radiation pneumonitis in 4%. There were 4 treatment related deaths due to late toxicities such as esophageal fistula, radiation pneumonitis, and the other cardiopulmonary diseases. Of eligible 74 patients, there were 50 complete responses (CRs) with a CR rate of 68% (95% Confidence Interval (CI): 56–78%). Median survival time was 31 months and the 2, 3-year survival rates were 55% (95% CI: 43–67%), 47% (95% CI: 36–59%), respectively. Conclusion: CRT for stage II, III ESCC is effective with acceptable acute toxicities, however, careful follow up is necessary for late toxicities. No significant financial relationships to disclose.

scholarly journals Stereotactic Body Radiotherapy for Metastatic and Recurrent Soft Tissue Sarcoma

2020 ◽  
Author(s):  
Xiaoyao Feng ◽  
Jing Li ◽  
Aomei Li ◽  
Han Zhou ◽  
Xixu Zhu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Hematogenous Metastasis ◽  
Invasive Growth ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Transformation

Abstract BackgroundSoft tissue sarcoma（STS） is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biologic pattern and clinical transformation with localized invasive growth and susceptibility to hematogenous metastasis. Metastatic and recurrent soft tissue sarcoma may be treated by local therapeutic options, including surgery and radiation therapy. This study evaluated the safety and efficacy of SBRT for metastatic and recurrent soft tissue sarcoma.MethodsWe performed a retrospective analysis of 37 STS patients with 58 lesions treated with SBRT from 2009-2019 at our institution. We analyze the local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates of the patients.ResultThe median follow-up was 20 months（range 2 to 120 months）. One and two year LC rates were 75.3% and 55.2% [95% confidence interval (CI) 20–25 months]. Median OS was 24 months and the survival rates were 66.6%, 45% and 26.6% at 1, 2 and 3-year after SBRT. Median PFS were 11months (95% CI 8–18 months). No acute or chronic grade ≥ 3 toxicity was observed.ConclusionsIn patients with metastatic and recurrent STS, LC, OS and PFS were higher than expected. SBRT should be a proper treatment option for STS.

Treatment-free survival after discontinuation of immuno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: Retrospective study of Japanese metastatic renal cell carcinoma patients (after I-O study).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 677-677
Author(s):  
Yoshihiko Tomita ◽  
Go Kimura ◽  
Satoshi Fukasawa ◽  
Yutaka Sugiyama ◽  
Kazuyuki Numakura ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3

677 Background: Guidelines for treatment of metastatic renal cell carcinoma (mRCC) recommend nivolumab monotherapy (NIVO) for treated mRCC, and nivolumab + ipilimumab combination therapy (NIVO+IPI) for untreated IMDC intermediate and poor risk mRCC patients. Though molecular targeted therapies (TTs) such as VEGFR-TKIs and mTORi are recommended as subsequent therapy after NIVO or NIVO+IPI, their impact is still unclear. Methods: Japanese mRCC patients treated with TT after NIVO (CheckMate 025) or NIVO+IPI (CheckMate 214) were retrospectively analyzed. Primary endpoints were investigator assessed ORR of the first TT after NIVO, and after NIVO+IPI. Secondary endpoints included treatment-free survival (TFS) after discontinuation of NIVO and NIVO+IPI, and progression-free survival (PFS) and safety of the first subsequent TT after NIVO and NIVO+IPI. Results: Twenty-six patients of CheckMate 025 and 19 patients of CheckMate 214 from 20 centers in Japan were analyzed. Median TFS after ICI discontinuation was 1.0m and 2.5m for CheckMate 025 and CheckMate 214 patients, respectively. Median follow-up period from the start of TT after ICI discontinuation to date of analysis or death was 22.1m for CheckMate 025, and 20.3m for CheckMate 214 patients. As the first subsequent TT after NIVO or NIVO+IPI, axitinib was the most treated therapy for both CheckMate 025 (53.8%) and CheckMate 214 (47.4%) patients. ORR of TT after NIVO and NIVO+IPI was 26.9% and 31.6%, and median PFS was 8.9m and 16.3m, respectively. During the treatment of first TT after NIVO and NIVO+IPI, 98% percent experienced treated-related adverse events, 51% experienced grade 3-4, but no treatment related death. Conclusions: TTs have favorable antitumor activity for mRCC after NIVO and NIVO+IPI, possibly by changing the mode of action. Safety signals of TTs after ICI were similar to the previous reports. These results indicate sequential TTs after ICI may contribute for durable survival benefit.

scholarly journals Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment

Leukemia ◽  
2020 ◽  
Vol 34 (12) ◽  
pp. 3286-3297 ◽  
Author(s):  
David S. Siegel ◽  
Gary J. Schiller ◽  
Christy Samaras ◽  
Michael Sebag ◽  
Jesus Berdeja ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Refractory Multiple Myeloma ◽  
Secondary Endpoints ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Treatment Emergent Adverse Event

AbstractPatients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1–21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Per protocol, all patients (N = 112) had received lenalidomide in their most recent prior regimen (75.0% lenalidomide refractory). ORR was 77.7% (76.2% in lenalidomide-refractory patients); median follow-up was 17.2 months. Median PFS was not reached (1-year PFS rate 75.1%). The most common hematologic grade 3/4 treatment-emergent adverse event was neutropenia (62.5%). Grade 3/4 infections were reported in 31.3% of patients, including 13.4% with grade 3/4 pneumonia. These results demonstrate the safety and efficacy of pomalidomide-based therapy as early as second line in patients with RRMM, even immediately after lenalidomide failure, indicating that switching from the immunomodulatory agent class is not necessary.

A phase 2 study of s-1 plus leucovorin in patients with untreated advanced cholangiocarcinoma (CCA).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 467-467
Author(s):  
Suebpong Tanasanvimon ◽  
Teerapat Ungtrakul ◽  
Nattaya Poovorawan ◽  
Napa Parinyanitikul ◽  
Chanida Vinayanuwattikun ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3

467 Background: Patients with CCA usually present with advanced disease leading to the grave prognosis. Currently, cisplatin and gemcitabine is the standard treatment in advanced CCA. However, the CCA treatment outcomes are still poor and the options of treatment are quite limited. This study aimed to explore the efficacy and safety of S-1 plus leucovorin in patients with untreated advanced CCA. Methods: This single-arm two-center phase 2 study evaluated the efficacy and safety of S-1 40, 50 and 60 mg according to body surface area and leucovorin 15 mg , both given orally twice daily for one week, repeated every two weeks. Treatment was continued until complete 12 cycles, disease progression or unacceptable toxicity. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST version 1.1. The secondary endpoints were progression free survival (PFS), overall survival (OS) and toxicity. Results: Of total 32 patients and a median follow up time of 9.5 months, the ORR was 25% (95%CI 9.1-40.9) and the DCR was 62.5% (95% CI 44.8-80.2). In 25 response evaluable patients, the ORR was 32% (95% CI 12.4-51.7). The PFS was 8.0 (95%CI 5.59-10.4) months. The OS was 11.0 (95%CI 9.47-12.53). The most common grade 3 or 4 toxicities were anemia, mucositis and diarrhea. There was one patient discontinuing treatment due to treatment related toxicity. Conclusions: S-1 plus leucovorin was active and tolerable in patients with advanced CCA. Clinical trial information: TCTR20160313001.

scholarly journals Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial

2009 ◽  
Vol 27 (21) ◽  
pp. 3472-3479 ◽  
Author(s):  
Jane F. Apperley ◽  
Jorge E. Cortes ◽  
Dong-Wook Kim ◽  
Lydia Roy ◽  
Gail J. Roboz ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Myelogenous Leukemia ◽  
Imatinib Treatment ◽  
Free Survival ◽  
Imatinib Resistant ◽  
Grade 3 ◽  
Experienced Treatment

PurposePatients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population.Patients and MethodsPatients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily.ResultsAt a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%).ConclusionDasatinib is effective in patients with CML-AP after imatinib treatment failure.

Phase II study of eribulin and pembrolizumab in patients (pts) with metastatic soft tissue sarcomas (STS): Report of LMS cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11559-11559
Author(s):  
Michael Nathenson ◽  
Edwin Choy ◽  
Neena D Carr ◽  
Hayley D Hibbard ◽  
Emanuele Mazzola ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prior Therapy ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Unacceptable Toxicity

11559 Background: Responses to single agent PD-1/PD-L1 inhibitors in STS remain limited with occasional responses in undifferentiated pleomorphic sarcomas (UPS), liposarcomas (LPS), and other sarcomas, and rare responses in leiomyosarcoma (LMS). Since cytotoxics and/or targeted therapies such as CDK4/6 inhibitors may alter the tumor microenvironment (TME) and potentiate the effect of immunotherapy, combination approaches may be needed to potentiate STS immunotherapy. The mechanism by which eribulin controls LPS may involve TME modification, and therefore it is attractive to test in combination with pembrolizumab in STS subtypes. This report summarizes the results from the LMS cohort from this ongoing trial. Methods: Pts treated with at least one prior therapy received eribulin 1.4mg/m2 (day 1, 8) and pembrolizumab 200mg (day 1), every 21 days. Pts continued therapy until progressive disease, death, or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) at 12 weeks, with 60% PFS at 12 weeks required to deem the combination promising. Tumor assessments (RECIST 1.1) were performed at screening and every 6 weeks thereafter. Secondary endpoints included overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Results: Nineteen pts with LMS were enrolled from May 2019 to Sept 2019. The median age was 62 (range 48-80). Eleven (58%) patients had uterine LMS. The median # of prior therapies was 4 (range 1-7). The median follow-up was 19.7 weeks. The PFS at 12 weeks was 42.1% (90% CI: 27.0%-65.5%), with median PFS of 11.1 weeks. Median OS was not reached during the follow-up period. There was 1 partial response, and 5 confirmed stable disease for ORR of 5.3% and CBR of 26.3%, after 12 weeks. The rate of grade 3 or higher toxicity was 68% overall, most commonly neutropenia, anemia, weight loss, diarrhea, elevations of lipase, and alkaline phosphatase. These side effects were reversible. The most common adverse events were fatigue, neutropenia, anorexia, AST increase, and nausea. Conclusions: Eribulin and pembrolizumab in LMS did not meet the predefined endpoint for efficacy. The LPS and “other STS subtype” cohorts of this trial are actively enrolling. Clinical trial information: NCT03899805 .

Evolution of Surgical Approaches in the Treatment of Petroclival Meningiomas: A Retrospective Review

2007 ◽  
Vol 61 (suppl_5) ◽  
pp. ONS202-ONS211 ◽  
Author(s):  
Nicholas C. Bambakidis ◽  
U. Kumar Kakarla ◽  
Louis J. Kim ◽  
Peter Nakaji ◽  
Randall W. Porter ◽  
...  
Keyword(s):  
Survival Rates ◽  
Progression Free Survival ◽  
Surgical Approaches ◽  
Single Institution ◽  
Short Term ◽  
Total Resection ◽  
Free Survival ◽  
Petroclival Meningioma ◽  
Petroclival Meningiomas

Abstract Objective: We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time. Methods: Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression. Conclusion: Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.

scholarly journals FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Jane E. Rogers ◽  
Michael Lam ◽  
Daniel M. Halperin ◽  
Cecile G. Dagohoy ◽  
James C. Yao ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Prior Therapy ◽  
Well Differentiated ◽  
Grade 3 ◽  
Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

scholarly journals Time to Progression Post-Induction Predicts Outcomes of Ixazomib Based Therapy for Relapsed/Refractory Myeloma: Real World Data from a Multi-Site Israeli Registry Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1972-1972
Author(s):  
Yael C Cohen ◽  
Hila Magen ◽  
Noa Lavi ◽  
Moshe E. Gatt ◽  
Evgeni Chubar ◽  
...  
Keyword(s):  
Research Funding ◽  
Overall Response Rate ◽  
Target Organ Damage ◽  
Progression Free Survival ◽  
Organ Damage ◽  
Real World Data ◽  
Free Survival ◽  
Grade 3 ◽  
Indolent Disease

Abstract Introduction Ixazomib is an orally available proteasome inhibitor, shown to be safe and efficacious in combination with lenalidomide and dexamethasone (IRd regimen) in patients with relapsed and refractory multiple myeloma (RRMM) with 1-3 prior lines, demonstrating a progression free survival (PFS) benefit which was similar across cytogenetic risk groups (Tourmaline-MM1 phase 3 trial). A European real world data analysis of an IRd named patient program (NPP) outcomes in Greece (n=35), UK (n=46) and Check republic (n=57) showed similar favorable outcomes (Terpos et al, Blood 2017 130:3087). We aimed to analyze outcomes of ixazomib combinations among a multi-site cohort in the Israeli Myeloma registry. Overall response rate (ORR) was classified according to IMWG criteria. Primary endpoint was PFS, secondary endpoints included ORR, overall survival (OS), safety and tolerability. Patients A total of 78 patients across 7 sites, who received at least one cycle of ixazomib combination between June 2013 and June 2018 for treatment of RRMM were retrospectively included. Median age was 68 (range: 38-90). Male/Female ratio was 42/36. ISS (rISS) I/II/II was 30%/42%/27% (25%/54%/15%). Patient received between 1 and 7 prior lines of therapy, 66% received ixazomib in 2nd line, 18% in 3rd line. Overall, 89% of patients had been exposed to PIs (bortezomib 86%) prior to IRd, 41% to IMiDs (thalidomide 28% lenalidomide 22% and pomalidomide 6%), and 35% had undergone autologous transplantation (ASCT). Induction treatment was mostly bortezomib based (85%), most frequently VCD (62%). FISH cytogenetics were available for 60 patients, 29 (48%) had high or intermediate risk aberrations (t(4:14) 12 pts, amp 1q21 12 pts, del17p 9 pts). Disease aggressiveness was classified by treating physician as indolent (rapid control to protect from target organ damage not required) vs aggressive (imminent target organ damage) in 63% vs 27%, respectively. 60 (77%) of the 78 patients received ixazomib via a named patient program, the rest via national or private healthcare provider. Results Median time of follow up from first ixazomib dose was 22 months (range: 1-39 months), and 54 months from diagnosis of myeloma. Treatment is ongoing in 44 (56%) patients with a median duration of 19 months (range: 1-29). Among patients who discontinued treatment, the median duration was 9 months (1-31). Ixazomib was combined with lenalidomide, pomalidomide, and daratumumab in 69%, 9% and 4%, respectively. Overall response rate was 88% - CR 10%, VGPR 36%, PR 42%. Progression free survival was 78% and 54% at 12 and 24 months, respectively (fig1a). A worse PFS was found with physician assessment of aggressive vs indolent disease (14.5 vs 25.9 months, p=0.001), and with post induction progression free period (PFS1) ≤ 24 months vs. >24 months (23.9 vs 31.5 months, p=0.038) (fig 1b); age >=65 trended towards a worse PFS (p=0.058). Poor cytogenetic risk, prior exposure to bortezomib, prior auto transplant, and number of prior lines of therapy did not affect PFS or ORR. OS from first ixazomib administration was 90% and 81% at 12 and 24 months, respectively; median OS was not reached (fig1a). Any (grade 3-4) toxicity considered by investigator as related to ixazomib was reported in 70% (18% grade 3-4), including neutropenia 14% (6%), anemia 19% (6%), thrombocytopenia 17% (5%), nausea and vomiting 17% (1%), DVT/PE 4% (1%), neutropenic infection 0 (4%), peripheral neuropathy 14% (3%), diarrhea 14% (3%), rash 10% (4%), pneumonia 5% (3%). There were no ixazomib related deaths. Dose reduction or discontinuation due to toxicity occurred in 28% and 12%, respectively. Conclusion Our data shows ixazomib-based combinations are efficacious and safe regimens for patients with RRMM, achieving ORR of 88%, at 2nd as well as later lines of therapy, regardless to cytogenetic risk. Over a median follow up of almost 2-years, 54% remained progression free at 24 months. An ixazomib based regimen may be particularly attractive for patients who remain progression free for more than 24 months after a bortezomib induction and for patients with a more indolent disease phenotype. Disclosures Cohen: Neopharm Israel: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Medisson Israel: Consultancy, Honoraria, Research Funding. Tadmor:NOVARTIS: Consultancy; PFIEZER: Consultancy; ABBVIE: Consultancy; JNJ: Consultancy; ROCHE: Research Funding.

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