scholarly journals Newly Diagnosed Myeloma in 2020

2020 ◽  
pp. e144-e158 ◽  
Author(s):  
Philippe Moreau ◽  
Cyrille Touzeau ◽  
Ravi Vij ◽  
Scott R. Goldsmith ◽  
Ashley E. Rosko
Keyword(s):  
Older Adults ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
New Agents ◽  
Specific Patient ◽  
Clinical Endpoints ◽  
Frontline Treatment ◽  
Treatment Tolerance

Over the last few years, there has been great progress in the treatment of multiple myeloma (MM), with many new agents and combinations having been approved and being now routinely incorporated into treatment strategies for newly diagnosed patients. As a result, patients are experiencing benefits in terms of survival and better tolerance. However, the multitude of treatment options also presents a challenge to select the best options tailored to the specific patient situation. Frontline autologous stem cell transplantation (ASCT) is the standard of care for fit patients younger than age 71 who are newly diagnosed with MM, and triplet combinations are the backbone of induction therapy before ASCT. Post-transplant consolidation and prolonged lower-intensity maintenance are two strategies that have been used to deepen responses and delay progression. For older patients not eligible for ASCT, lenalidomide (len) is increasingly being used as part of frontline therapy, and current approaches are now targeting combinations of anti-CD38 antibodies. Strategies for selecting therapeutic regimens for older adults newly diagnosed with MM can be augmented with use of predictive tools to better capture physiologic age and estimate treatment tolerance. Here we review a decade of trials identifying clinical endpoints and toxicities relevant for the frontline treatment of younger patients and older adults.

New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options

2022 ◽  
Author(s):  
Anne S. Tsao ◽  
Harvey I. Pass ◽  
Andreas Rimner ◽  
Aaron S. Mansfield
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Checkpoint Inhibitors ◽  
Treatment Plan ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Pleural Mesothelioma ◽  
Frontline Treatment ◽  
Rare Malignancy

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.

scholarly journals Clinical Characteristics and Outcomes of AML Patients Treated with Frontline CPX 351 or HMA/Venetoclax: A Single Institution's Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1252-1252
Author(s):  
Aleksander L. Chojecki ◽  
Justin Arnall ◽  
Danielle Boselli ◽  
Kristyn Y. DiSogra ◽  
Allison Karabinos ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
Treatment Options ◽  
Standard Of Care ◽  
Response Rates ◽  
Similar Response ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Frontline Treatment ◽  
To Receive

Abstract Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P<0.001); many pts in both treatment groups had unfavorable ELN risk scores at diagnosis (CPX 43%, HMA/Ven 41%; P>0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P<0.001). No differences were detected in achievement of MRD negativity by flow cytometry (P=0.51) or molecular profile (P=0.52). Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy.

scholarly journals Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: A population-based study

2021 ◽  
Author(s):  
Akira Sato ◽  
Keisuke Matsubayashi ◽  
Toshitaka Morishima ◽  
Kayo Nakata ◽  
Koji Kawakami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Research ◽  
Cancer Patients ◽  
Uterine Cancer ◽  
Treatment Options ◽  
Temporal Trends ◽  
Treatment Strategies ◽  
Population Based ◽  
Trend Test ◽  
Newly Diagnosed

Abstract Background: Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan. Methods: Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test. Results: Among 275,720 newly diagnosed cancer patients, 21,784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer. Conclusions: The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options.

scholarly journals Towards Personalization in the Curative Treatment of Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Astrid E. Slagter ◽  
Marieke A. Vollebergh ◽  
Edwin P. M. Jansen ◽  
Johanna W. van Sandick ◽  
Annemieke Cats ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Molecular Characteristics ◽  
Perioperative Chemotherapy ◽  
Current Standard ◽  
Common Cancer ◽  
Resectable Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide and has a high mortality rate. In the last decades, treatment strategy has shifted from an exclusive surgical approach to a multidisciplinary strategy. Treatment options for patients with resectable gastric cancer as recommended by different worldwide guidelines, include perioperative chemotherapy, pre- or postoperative chemoradiotherapy and postoperative chemotherapy. Although gastric cancer is a heterogeneous disease with respect to patient-, tumor-, and molecular characteristics, the current standard of care is still according to a one-size-fits-all approach. In this review, we discuss the background of the different treatment strategies in resectable gastric cancer including the current standard, the specific role of radiotherapy, and describe the current areas of research and potential strategies for personalization of therapy.

scholarly journals Undertreatment of Older Patients with Newly-Diagnosed Multiple Myeloma: Real World Evidence from a Canadian Registry Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 268-268 ◽  
Author(s):  
Hira S Mian ◽  
C. Tom Kouroukis ◽  
Gregory R Pond ◽  
Hsien Seow ◽  
Jonathan Sussman
Keyword(s):  
Older Adults ◽  
Multiple Myeloma ◽  
Real World ◽  
Older Patients ◽  
Treatment Options ◽  
Newly Diagnosed ◽  
Drug Usage ◽  
Novel Drugs ◽  
One Year ◽  
Novel Drug

Introduction Multiple myeloma (MM) is a malignant plasma cell disease and is considered a disease of older patients as the median age at diagnosis is 70 years. In recent years, the overall survival of patients with MM has improved due to the increasing number of treatment options and better supportive care. However, older patients (age &gt;65) have not benefitted equally from the same gains. There is a paucity of information regarding clinical outcomes in this age cohort given that older patients are often under-represented in clinical trials and prospective studies. Real-world data may allows us to examine the trends in practice patterns over time and help us understand disparities in treatment options and overall patient outcomes in older patients with MM at a population level. Methods We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly-diagnosed multiple myeloma, identified using the ICD-O-3 code 9732/3 (Multiple Myeloma) between the years 2007-2017, were included to form the cohort. Autologous transplant within one year of diagnosis was captured in the database using a combination of physician billing codes and hospital procedure/discharge codes. Novel drugs usage for transplant ineligible patients was defined as the receipt of thalidomide, lenalidomide and bortezomib in any combination within one year of diagnosis. No treatment was defined as patients that did not receive a transplant, novel drugs or non-novel drugs (melphalan and cyclophosphamide) within one year following diagnosis. Results A total of 11,875 patients with newly-diagnosed myeloma were identified between the years 2007-2017. The proportion of newly-diagnosed MM patients who were older (age &gt;65 years) increased from 60% of those diagnosed in 2007 to 68% of those diagnosed in 2017. The rates of autologous transplantation in older patients with MM increased from 4 to 10%. Overall those who underwent transplant had improved outcomes with decreasing one-year mortality from nearly 24% in 2007 down to 3% in 2017. Novel drugs were increasingly being used in older patients that were transplant ineligible with up to 42% receiving it within one year of diagnosis in 2017. In transplant ineligible older adults using novel drugs, one- year mortality ranged from 15% to 24%. The rates of older adults with newly-diagnosed MM not treated within one year of diagnosis was on average 49% although that number marginally declined from 54% in 2007 to 47% in 2017. Among those that did not receive treatment, 48% of individuals on average (range 40-57%) were not alive at one-year following diagnosis. Conclusion Our results demonstrate that although gains are being made in older adults with newly-diagnosed MM with increasing rates of transplantation and novel-drug usage over the last decade, there remains a sizeable cohort of older patients that do not receive any treatment within one year of diagnosis. While a limitation of our study may be the inclusion of some smouldering cases of myeloma, the mortality for older patients not treated continues to remain high with approximately half the patients not alive at one year following diagnosis. This study represents one of the largest cohort studies done to date over a decade demonstrating the ongoing low rates of no treatment and high rates of one-year mortality for older patients with MM. Further identification of factors associated with no treatment, transplantation and novel drug usage in older patients with MM are currently being explored. Table. Disclosures Mian: Amgen: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pond:Roche Canada: Employment, Other: Stock; Takeda (DSMC membership): Other: Honorarium.

scholarly journals Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: a population-based study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Akira Sato ◽  
Keisuke Matsubayashi ◽  
Toshitaka Morishima ◽  
Kayo Nakata ◽  
Koji Kawakami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Research ◽  
Cancer Patients ◽  
Uterine Cancer ◽  
Treatment Options ◽  
Temporal Trends ◽  
Treatment Strategies ◽  
Population Based ◽  
Trend Test ◽  
Newly Diagnosed

Abstract Background Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan. Methods Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test. Results Among 275,720 newly diagnosed cancer patients, 21,784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer. Conclusions The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options.

Carfilzomib PLUS Melphalan and Prednisone (CMP) Is A Promising Combination Therapy For The Treatment Of Elderly Patients With NEWLY Diagnosed Multiple Myeloma: Results Of A PHASE I/II Trial In 68 CASES

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1933-1933 ◽  
Author(s):  
Philippe Moreau ◽  
Brigitte Kolb ◽  
Cyrille Hulin ◽  
Denis Caillot ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Phase I ◽  
Standard Of Care ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Newly Diagnosed ◽  
Safety And Efficacy ◽  
Frontline Treatment ◽  
Grade 3

Abstract Melphalan-Prednisone + bortezomib (MPV) is one of the standard of care for the frontline treatment of patients with symptomatic multiple myeloma non eligible for high-dose therapy. In the pivotal VISTA trial for approval of MPV, the main toxicity was grade 3-4 peripheral neuropathy (PN) described in 14% of the cases. Carfilzomib (CFZ), the second-in-class proteasome inhibitor has shown promising activity and a favorable toxicity profile with low PN rates. Therefore, the option of combining CFZ with MP (CMP) is an attractive one. Therefore we designed a phase I/II study to determine the maximum tolerated dose (MTD) of CMP and to assess safety and efficacy. In the phase I portion of the trial, CFZ was started at 20mg/m2, then escalated to 27, 36, and 45mg/m2, administered IV over 30 minutes in 42-day cycles on D1/2/8/9/22/23/29/30 for 9 cycles. Melphalan 9mg/m2 and prednisone 60mg/m2 were given PO D1–4 of every 42-day cycle. MTD was based on dose-limiting toxicity (DLT) in cycle 1 defined as any grade 4 (G4) hematologic adverse event (AE), any hematologic AE preventing aministration of ≥ 2 CFZ doses except G4 thrombocytopenia without bleeding or G4 neutropenia ≤ 7days, ≥ G3 febrile neutropenia, or any ≥G3 nonhematologic AE. As of July 6, 2013, 24 pts have been enrolled in phase I: 6 for each dose level. There were 2 DLTs at 45mg/m2 (fever plus hypotension) resulting in a MTD of 36mg/m2. In Phase II, 44 additional patients received CMP at 36mg/m2 CFZ for N=68 total PhI/II patients (50 patients overall treated at the dose pf 36mg/m2). The median age of the series was 72 years, with 36% of the patients presenting with ISS3. Overall response rate was 89.5% including 56% ≥ very good partial response. With a median follow-up of 12 months, the projected 2y OS was 87%, and the median event-free survival was 22 months. CMP was well tolerated and only 1 patient developed grade 3 PN. These promising results compare favorably to those of MPV, MP+Thalidomide, MP+lenalidomide (R), and R+dex in similar pts. CFZ 36mg/m2 + MP is tolerable and effective in elderly patients with symptomatic newly diagnosed MM. Treatment is ongoing, 20% of the patients are receiving their last cycles of CMP. Final safety and efficacy data will be presented during the meeting. Disclosures: Moreau: CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Off Label Use: FRONTLINE TREATMENT WITH CARFIZOMIB. Hulin:CELGENE: Honoraria; JANSSEN: Honoraria. Leleu:CELGENE: Honoraria; JANSSEN: Honoraria. Roussel:CELGENE: Honoraria; JANSSEN: Honoraria. Attal:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Facon:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

Individualizing Treatment Decisions for Older Adults with Hematologic Malignancies

2013 ◽  
pp. 208-219
Author(s):  
Heidi D. Klepin ◽  
David Rizzieri ◽  
Antonio Palumbo ◽  
Valeria Magarotto ◽  
Barbara Eichhorst
Keyword(s):  
Older Adults ◽  
Treatment Options ◽  
Allogeneic Bone Marrow Transplantation ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Allogeneic Bone ◽  
Functional Impairments ◽  
Therapeutic Decisions

Hematologic malignancies are a common cause of morbidity and mortality among older adults, who represent the majority of patients diagnosed with these diseases. Treatment options and disease outcomes have improved in recent years because of the development of novel treatment strategies and the design of elderly-specific clinical trials. Despite this, extrapolation of clinical trial data to patients routinely seen in practice is challenging because of the presence of multimorbidity and functional impairments. Individualized treatment decision making requires not only an understanding of underlying tumor biology but also careful estimation of an older patient's anticipated ability to withstand the stresses of therapy. This article will discuss approaches to standardizing patient assessment strategies and tailoring therapeutic decisions for older adults with hematologic malignancies with a focus on acute myeloid leukemia (AML), allogeneic bone marrow transplantation, multiple myeloma (MM), and chronic lymphocytic leukemia (CLL).

scholarly journals Endoscopic Double Stenting for the Management of Combined Malignant Biliary and Duodenal Obstruction

2021 ◽  
Vol 10 (15) ◽  
pp. 3372
Author(s):  
Tsuyoshi Takeda ◽  
Takashi Sasaki ◽  
Takeshi Okamoto ◽  
Naoki Sasahira
Keyword(s):  
Duodenal Obstruction ◽  
Performance Status ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Technical Difficulty ◽  
Periampullary Cancer ◽  
High Morbidity ◽  
Current Standard ◽  
Surgical Bypass

Periampullary cancers are often diagnosed at advanced stages and can cause both biliary and duodenal obstruction. As these two obstructions reduce patients’ performance status and quality of life, appropriate management of the disease is important. Combined malignant biliary and duodenal obstruction is classified according to the location and timing of the duodenal obstruction, which also affect treatment options. Traditionally, surgical bypass (gastrojejunostomy and hepaticojejunostomy) has been performed for the treatment of unresectable periampullary cancer. However, it has recently been substituted by less invasive endoscopic procedures due to its high morbidity and mortality. Thus, endoscopic double stenting (transpapillary stenting and enteral stenting) has become the current standard of care. Limitations of transpapillary stenting include its technical difficulty and the risk of duodenal-biliary reflux. Recently, endoscopic ultrasound-guided procedures have emerged as a novel platform and have been increasingly utilized in the management of biliary and duodenal obstruction. As the prognosis of periampullary cancer has improved due to recent advances in chemotherapy, treatment strategies for biliary and duodenal obstruction are becoming more important. In this article, we review the treatment strategies for combined malignant biliary and duodenal obstruction based on the latest evidence.

Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8000-8000 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Ajai Chari ◽  
Sagar Lonial ◽  
Brendan M. Weiss ◽  
Raymond L. Comenzo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Safety Profile ◽  
Standard Of Care ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Open Label ◽  
Frontline Treatment ◽  
Grade 3

8000 Background: DARA in combination with established standard of care regimens prolongs PFS, deepens responses, and demonstrates a favorable safety profile in relapsed or refractory multiple myeloma (MM). The tolerability and efficacy of DARA-KRd in newly diagnosed MM pts was examined. Methods: Newly diagnosed pts regardless of transplantation eligibility were enrolled. Pts received DARA 16 mg/kg QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter. All pts received the 1st dose of DARA split over 2 days. Carfilzomib (K) was administered on Days 1, 8 and 15 of each 28-day cycle (20 mg/m2 on C1D1, 36 or 70 mg/m2 subsequently based on tolerability of first dose) for ≤13 cycles or elective discontinuation for ASCT. Lenalidomide 25 mg was given on Days 1-21 and dexamethasone 20-40 mg per week. The primary endpoint was tolerability. Results: Twenty-two pts (median [range] age, 60 [34-74] y) were enrolled and received a median of 8 (1-10) treatment cycles. Nineteen pts escalated K dose to 70 mg/m2 by C1D15. Median (range) duration of follow-up was 7.4 (4.0-9.3) months. Six (27%) pts discontinued treatment (1 AE [pulmonary embolism]; 1 PD; 4 other [ASCT]). Serious AEs occurred in 46% of pts, and 14% were possibly related to DARA; 18 (82%) experienced a grade 3/4 TEAE. The most common grade 3/4 TEAEs (>10%) were lymphopenia (50%) and neutropenia (23%); 1 (5%) cardiac grade 3 TEAE was observed (congestive heart failure) which resolved; pt quickly resumed study treatment with reduced K dose. No grade 5 TEAE was reported. All DARA-associated infusion reactions (27% of pts) were grade ≤2. Treatment with DARA-KRd yielded an ORR (≥partial response) of 100% (5% complete response, 86% ≥very good partial response) in 21 response-evaluable pts. The 6-month PFS rate was 100%. Conclusions: The addition of DARA to KRd was well tolerated; the overall safety profile was consistent with that previously reported for KRd, with no additional toxicity observed with the addition of DARA. Deep and durable responses were observed. These data support further investigation of DARA-KRd as a frontline treatment regimen. Updated data will be presented based on longer follow up. Clinical trial information: NCT01998971.

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