DOCSLIB.ORG

Chronic Lymphocytic Leukemia (CLL) Natural History

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chronic Lymphocytic Leukemia (CLL) Natural History CHRONIC LYMPHOCYTIC LEUKEMIA & SMALL LYMPHOCYTIC LYMPHOMA New Treatment Options in 2020 Parameswaran Venugopal, MD Professor of Medicine The Elodia Kehm Chair in Hematology Director, Section of Hematology September 16, 2020 Chronic Lymphocytic Leukemia (CLL) Natural History CLL impacts survival for all age groups <75 • Most common type of leukemia – ~10,000 cases/year • Common in the elderly – Median age in the 7th decade of life • Often asymptomatic • Median survival – Low risk (Rai 0): >10 years – Intermediate risk (Rai I/II): 5-7 years – High risk (Rai III/IV): 1-3 years Stilgenbauer, et al. Hematology. Am Soc Hematol Educ Program. 2004;163. 2 Shanafelt T, et al. Cancer. 2010:116:4777. Maurer, et al. ASH 2014. Chronic Lymphocytic Leukemia Statistics SEER Cancer Statistics: Cancer Stat Facts: Leukemia — Chronic Lymphocytic Leukemia (CLL). Chronic Lymphocytic Leukemia How is CLL diagnosed? Blood Smear in CLL Blood counts Blood Smear Flowcytometry Chronic Lymphocytic Leukemia What is my prognosis? Chronic Lymphocytic Leukemia Prognostic Factors Prognostic Feature Associated With Poor Prognosis CD38 expression on CLL cells High CD38 expression (30%) Chromosome Study Zap-70 expression on CLL cells High Zap-70 expression (20%) IGHV mutation status FISH Unmutated CLL Serum β2 macroglobulin PCR Elevated (3.5 mg/L) FISH cytogenetics Mutation Analysisdel(17p), del(11q) Gene mutations NGSTP53, NOTCH1, BIRC3, SF3B1, or ATM Rai KR, Jain P. Am J Hematol. 2016;91:330-340. CLL: Prognostic Value of FISH • Deletions on the long arm of chromosome 13 is most commonly observed (55% of all cases) – Isolated del(13q14) is associated with a benign disease course • 17p deletion and/or TP53 mutation is an adverse prognostic feature, predicting for inferior responses and survival in CLL – Lower responses to chemoimmunotherapy • Important to obtain at diagnosis and should be repeated before subsequent therapies as additional genetic abnormalities may be acquired Dohner et al, N Engl J Med. 2000;343:1910. Chronic Lymphocytic Leukemia What are the indications for starting treatment? NCI-WG Indications to Treat • Constitutional symptoms referable to CLL • Progressive marrow failure • AutoimmuneObservation anemia +/- isthrombocytopenia appropriate poorly in responsivethe to corticosteroids absence of indication for therapy • Massive or progressive splenomegaly • Massive or progressive lymphadenopathy • Progressive lymphocytosis Cheson BD et al. Blood. 1996;87:4990-4997. First-Line Treatment • Chemotherapy • Monoclonal Antibodies • Combinations: – FCR, BR • Ibrutinib (Imbruvica) • Acalabrutinib (Calquence) • Venetoclax (Venclexta) • Clinical Trials 11 Timeline of New Agents for CLL Obinutuzumab TN: w/Ibrutinib; w/Chlorambucil Idelalisib R/R: w/Rituximab Venetoclax Duvelisib R/R: Monotherapy & w/Rituximab R/R 2013 2014 2015 2016 2017 2018 2019 2020 Ibrutinib Ofatumumab Acalabrutinib TN: Monotherapy; w/Obinutuzumab TN: w/Chlorambucil TN: Monotherapy; w/Obinutuzumab R/R: Monotherapy R/R: Monotherapy; w/FC R/R: Monotherapy CAR T-cells Not yet approved for CLL TN, treatment naïve; R/R, relapsed/refractory; FC, fludarabine and cyclophosphamide (FC) 12 Targeted Treatment Options for CLL Copanlisib Obinutuzumab Duvelisib Ofatumumab Idelalisib Rituximab Umbralisib Ublituximab Acalabrutinib ARQ 531 Ibrutinib LOXO-305 Tirabrutinib Vecabrutinib Zanubrutinib Agents listed in bold are FDA approved Venetoclax Figure adapted from Crisci, et al. Front. Oncol. 2019. doi.org/10.3389/fonc.2019.00443 BTK Inhibitors Mechanism of Action • Selective tyrosine kinase inhibitors (TKIs) BTK Inhibitors • Acalabrutinib, Ibrutinib, Zanubrutinib: Forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity • Vecabrutinib, LOXO-305, ARQ 531: Noncovalent binding to BTK • Blocks B-cell receptor signaling and survival, proliferation, and migration of cancerous B cells Figure from Bond DA et al. Clin Advances Hematol Oncol 2019 Summary of FDA-Approved BTK Inhibitors Ibrutinib Acalabrutinib Zanubrutinib • CLL (monotherapy or w/ • CLL/SLL (monotherapy • R/R MCL obinutuzumab or rituximab) or with obinutuzumab) • R/R MCL • R/R MCL (monotherapy) FDA-approved • WM indications • MZL (after ≥ 1anti-CD20-based therapy) • cGVHD • CLL/SLL, WM, and cGVHD: 420 Method of mg taken orally once daily 100 mg every 12 hours Once daily (320 mg) or administration • MCL and MZL: 560 mg taken orally twice daily (160 mg) orally orally once daily • Bleeding, atrial fibrillation, • Headaches, diarrhea, • Diarrhea, infection, Key toxicities diarrhea, fatigue, and increased fatigue, infection, anemia fatigue, anemia risk for infection Owen, et al. Curr Oncol. 2019; 26(2): e233–e240. doi: 10.3747/co.26.4345 8-Year Follow-up of Ibrutinib Monotherapy: High Rates of OS, ORR and Long-term Tolerability in CLL PFS OS First-line First-line First-line R/R Median, mos Median, mos 7-year PFS 7-year OS (95%CI) (95%CI) First-line (n=31) NR (NE-NE) 83% First-line (n=31) NR (NE-NE) 84% Byrd, et al. Clin Cancer Res. 2020 Mar 24; clincanres.2856.2019. doi: 10.1158/1078-0432.CCR-19-2856. Phase 3 RESONATE-2: 5-Year Update Ibrutinib Provides Durable Response as Initial Therapy in Frail Pts Efficacy • Ibrutinib benefit was also consistent Ibrutinib in patients with high prognostic risk (TP53 mutation, 11q deletion, and/or unmutated IGHV) Safety Chlorambucil • Discontinuation due to AEs decreased over time, with 58% of ibrutinib pts continuing daily treatment Median PFS, mo HR (95% CI) Ibrutinib NE 0.146 (0.098-0.218) Chlorambucil 15.0 Burger JA, et al. Leukemia. 2020;34(3):787-798. doi: 10.1038/s41375-019-0602-x. Chronic Lymphocytic Leukemia Three major studies in the past year that have influenced the first-line therapy of CLL in 2020 Obinutuzumab + Ibrutinib or Chlorambucil in Treatment-Naive CLL/SLL (Phase 3 iLLUMINATE) PFS per IRC in ITT Population PFS in High-Risk Population 100 100 80 79% 80 60 60 Free Survival (%) SurvivalFree (%) SurvivalFree - - 40 31% 40 Ibrutinib- Chlorambucil- Ibrutinib- Chlorambucil- Firstobinutuzumab obinutuzumabnon-chemotherapy combinationobinutuzumab obinutuzumab 20 20 Median (mo) NR 19.0 Median (mo) NR 14.7 Hazard ratio 0.231 (95% CI, 0.145–0.367); Hazard ratio 0.154 (95% CI, 0.087–0.270); Progression Progression P<0.0001 P<0.0001 0 0 0 3 6 approved9 12 15 18 21 24 by27 30 FDA33 36 - January0 3 6 9 12 201915 18 21 24 27 30 33 36 Months Months Obinutuzumab + Obinutuzumab + Ibrutinib Chlorambucil ORR per IRC (per investigator) 88% (91%) 73% (81%) CR/CRi per IRC (per investigator) 19% (41%) 8% (16%) Patients with undetectable MRD 35% 25% OS rate at 30 months 86% 85% High-risk population (del(17p)/TP53 mutation, del(11q), and/or unmutated IGHV. 19 Moreno C et al. ASH 2018. Abstract 691. IR vs FCR in Pts with Treatment-Naive CLL/SLL (Phase 3 ECOG-ACRIN E1912) Treatment-Naive CLL/SLL N=529 Ibrutinib (QD) + Rituximab (7 cycles) •CLL (IWCLL criteria), or SLL (WHO Primary Endpoints st criteria) 1 Interim Analysis n •Disease requiring treatment 2:1 Fludarabine + PFS, change in QoL •Age ≤70 years Randomizatio Cyclophosphamide •No deletion of Ibrutinib17p13 + Rituximab+ Rituximab (6 cycles) leads to •ECOG PS 0-2 PFS (All Randomized)better diseaseOS (Allcontrol Randomized) & survival HR=0.352; 95% CI, 0.223-0.558; P<0.0001 HR=0.168; 95% CI, 0.053-0.538; P=0.0003 • Median follow-up 33.4 months 100 compared100 to FCR 90 90 • PFS: IR was superior to FCR 80 80 70 70 independent of age, sex, PS, 60 60 stage or del11q23 50 50 presence/absence 40 40 30 30 • IR was superior to FCR for -6 -4 20 P=1.62 x 10 20 P=3.22 x 10 IR (37 events/354 cases) IR (4 deaths/354 cases) IGHV unmutated, but not 10 FCR (40 events/175 cases) 10 FCR (10 deaths/175 cases) mutated patients 0 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 20 Shanafelt TD et al. ASH 2018. Abstract LBA-4. BR vs IR vs Ibrutinib Alone in Older Patients with Treatment-Naive CLL (Phase 3 ALLIANCE A041202) Bendamustine + Treatment-Naive CLL Rituximab (6 cycles) N=523 Primary Endpoint •CLL (IWCLL criteria) n Ibrutinib (QD) 1st Interim Analysis •CLL requiring treatment (IWCLL criteria) PFS •Intermediate- or high-risk Rai stage Randomizatio Ibrutinib (QD) + Ibrutinib +/- RituximabRituximab leads(6 cycles) to better disease PFScontrol compared to Bendamustine + 100 90 87% Arm RituximabN 24-Month Estimate OS 80 IR 170 88% (95% CI: 81, 92%) 70 88% • No significant OS differences among I 178 87% (95% CI: 81, 92%) 60 arms 50 74% 40 BR 176 74% (95% CI: 66, 80%) • Median OS not reached for any arm 30 • 2-year OS estimates 20 Arm Events/Total % Alive and Progression-Free and Alive % 10 Arm A (BR) 68/176 Arm B (I) 34/178 – Arm 1 (BR) 95% Arm C (IR) 32/170 0 Censor 0 6 12 18 24 30 36 42 48 52 – Arm 2 (I) 90% Time (Months) Patients-at-Risk Arm A (BR) 176 140 129 122 103 88 57 26 11 0 – Arm 3 (IR) 94% Arm B (I) 178 165 154 147 136 120 78 45 22 0 Arm C (IR) 170 159 145 138 132 115 74 40 20 0 21 Woyach J, et al. N Engl J Med. 2018;379:2517-2528. doi: 10.1056/NEJMoa1812836 Treatment for Relapsed CLL • Chemotherapy • Monoclonal Antibodies – Ofatumumab (Arzerra) – Alemtuzumab (Campath) • Ibrutinib (Imbruvica) • Acalabrutinib (Calquence) • Venetoclax (Venclexta) • Clinical Trials • Stem Cell Transplantation 22 Ibrutinib is Superior to Ofatumumab in R/R CLL (Phase 3 RESONATE Final Results) CLL/SLL diagnosis Ibrutinib QD N=391 Crossover • ≥ 1 prior therapy upon PD • ECOG PS 0-1 Ofatumumab (300 mg followed by 2000 (n = 122) mg x 11 doses for 24 wks) • Measurable nodal disease by CT PFS OS Ibrutinib: mOS 67.7 mos Ibrutinib: mPFS 44.1 mos HR: 0.810 (0.602-1.091) HR: 0.148 (0.113-0.196) • Median follow-up 65.3 months • Long-term treatment with Ofatumumab: mOS 65.1 mos ibrutinib is tolerable and continues to show sustained Ofatumumab: mPFS 8.1 mos PFS and OS regardless of high-risk cytogenetics Munir, et al.
Load more

Recommended publications
  • Duvelisib Eliminates CLL B Cells, Impairs CLL- Supporting Cells, and Overcomes Ibrutinib Resistance in Preclinical Models
    Duvelisib Eliminates CLL B Cells, Impairs CLL- Supporting Cells, and Overcomes Ibrutinib Resistance in Preclinical Models Shih-Shih Chen ( [email protected] ) Karches Center for Oncology Research, the Feinstein Institutes for Medical Research Jacqueline Barrientos Karches Center for Oncology Research, the Feinstein Institutes for Medical Research Gerardo Ferrer Josep Carreras Leukaemia Research Institute (IJC) https://orcid.org/0000-0002-4084-6815 Priyadarshini Ravichandran Karches Center for Oncology Research, the Feinstein Institutes for Medical Research Michael Ibrahim Karches Center for Oncology Research, the Feinstein Institutes for Medical Research Yasmine Kieso Karches Center for Oncology Research, the Feinstein Institutes for Medical Research Jeff Kutok Innity Pharmaceuticals Marisa Peluso Innity Pharmaceuticals, Inc Sujata Sharma Innity Pharmaceuticals, Inc David Weaver Institute of Health Sciences, Anhui University Jonathan Pachter Verastem Inc. Kanti Rai The Karches Center for Oncology Research. The Feinstein Institutes for Medical Research. Nicholas Chiorazzi Karches Center for Oncology Research, the Feinstein Institutes for Medical Research Article Keywords: chronic lymphocytic leukemia, cancer therapy, Bruton’s Tyrosine Kinase (BTKi), phosphoinositide 3-kinase (PI3Ki) Page 1/23 Posted Date: July 21st, 2021 DOI: https://doi.org/10.21203/rs.3.rs-701669/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/23 Abstract Inhibitors of Bruton’s Tyrosine Kinase (BTKi) and phosphoinositide 3-kinase (PI3Ki) have signicantly improved therapy of chronic lymphocytic leukemia (CLL). However, the emergence of resistance to BTKi has introduced an unmet therapeutic need. Here we demonstrate in vitro and in vivo the essential roles of PI3K-δ for CLL B-cell survival and migration and of PI3K-γ in T-cell migration and macrophage polarization; and more ecacious inhibition in CLL-cell burden by dual inhibition of PI3K-δ,γ.
    [Show full text]
  • Minutes of the CHMP Meeting 14-17 September 2020
    13 January 2021 EMA/CHMP/625456/2020 Corr.1 Human Medicines Division Committee for medicinal products for human use (CHMP) Minutes for the meeting on 14-17 September 2020 Chair: Harald Enzmann – Vice-Chair: Bruno Sepodes Disclaimers Some of the information contained in these minutes is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the CHMP meeting highlights once the procedures are finalised and start of referrals will also be available. Of note, these minutes are a working document primarily designed for CHMP members and the work the Committee undertakes. Note on access to documents Some documents mentioned in the minutes cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on- going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006). 1 Addition of the list of participants Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020.
    [Show full text]
  • Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types?
    cancers Review Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types? Wout De Wispelaere 1 , Daniela Annibali 1,2 , Sandra Tuyaerts 1,3 , Diether Lambrechts 4,5 and Frédéric Amant 1,6,7,* 1 Department of Oncology, KU Leuven (University of Leuven) and Leuven Cancer Institute (LKI), 3000 Leuven, Belgium; [email protected] (W.D.W.); [email protected] (D.A.); [email protected] (S.T.) 2 Division of Oncogenomics, Antoni Van Leeuwenhoek—Netherlands Cancer Institute (AvL-NKI), 1066 CX Amsterdam, The Netherlands 3 Laboratory of Medical and Molecular Oncology (LMMO), Department of Medical Oncology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium 4 Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven (University of Leuven), 3000 Leuven, Belgium; [email protected] 5 VIB Center for Cancer Biology, Flemish Institute for Biotechnology (VIB), 3000 Leuven, Belgium 6 Centre for Gynecologic Oncology Amsterdam (CGOA), Antoni Van Leeuwenhoek—Netherlands Cancer Institute, University Medical Center (UMC), 1066 CX Amsterdam, The Netherlands 7 Department of Obstetrics and Gynecology, University Hospitals Leuven (UZ Leuven), 3000 Leuven, Belgium * Correspondence: [email protected] Simple Summary: Immune checkpoint blockade (ICB) has emerged as a very promising therapeutic option for patients, demonstrating unprecedented, durable responses in several difficult-to-treat Citation: De Wispelaere, W.; cancers. Despite research indicating a strong potential for ICB in uterine leiomyosarcomas (uLMSs), a Annibali, D.; Tuyaerts, S.; Lambrechts, clinical trial assessing response to ICB monotherapy in uLMSs showed no clinical benefit. Resistance D.; Amant, F. Resistance to Immune to ICB has been studied extensively in a variety of tumor types, but the resistance mechanisms Checkpoint Blockade in Uterine explaining the lack of response to ICB in uLMSs remain largely unexplored.
    [Show full text]
  • Duvelisib for Relapsed Chronic Lymphocytic Leukaemia – Second and Subsequent Line
    Horizon Scanning Research April 2016 & Intelligence Centre Duvelisib for relapsed chronic lymphocytic leukaemia – second and subsequent line LAY SUMMARY Chronic lymphocytic leukaemia is a type of cancer which usually develops very slowly. In people with chronic lymphocytic leukaemia, the body makes too many white blood cells called lymphocytes. These This briefing is based on lymphocytes are abnormal and do not work properly so build up in the information lymph nodes (glands), spleen, bone marrow and blood. Many patients available at the time who have chronic lymphocytic leukaemia are diagnosed when having of research and a a routine blood test and if well, usually do not need to start treatment limited literature straight away. However, if the disease starts to cause symptoms, search. It is not treatment is then required. intended to be a definitive statement Duvelisib is a new type of drug for patients with chronic lymphocytic on the safety, leukaemia given as a tablet twice a day. Some studies have efficacy or suggested duvelisib may be helpful for people whose first treatment effectiveness of the has failed and whose disease has continued to spread. More studies health technology are now aiming to show how well it works and that it is safe to use. covered and should not be used for If duvelisib is licensed for use in the UK, it could be a new treatment commercial option for patients with chronic lymphocytic leukaemia that may reduce purposes or symptoms of the disease and increase survival. commissioning without additional information. NIHR HSRIC ID: 9609 This briefing presents independent research funded by the National Institute for Health Research (NIHR).
    [Show full text]
  • Phase I/II Clinical Trial of Temsirolimus and Lenalidomide in Patients with Relapsed and Refractory Lymphomas by Ajay Major, Justin Kline, Theodore G
    Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas by Ajay Major, Justin Kline, Theodore G. Karrison, Paul A.S. Fishkin, Amy S. Kimball, Adam M. Petrich, Sreenivasa Nattam, Krishna Rao, Bethany G. Sleckman, Kenneth Cohen, Koen van Besien, Aaron P. Rapoport, and Sonali M. Smith Received: April 18, 2021. Accepted: July 22, 2021. Citation: Ajay Major, Justin Kline, Theodore G. Karrison, Paul A.S. Fishkin, Amy S. Kimball, Adam M. Petrich, Sreenivasa Nattam, Krishna Rao, Bethany G. Sleckman, Kenneth Cohen, Koen van Besien, Aaron P. Rapoport and Sonali M. Smith. Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas. Haematologica. 2021 Jul 29. doi: 10.3324/haematol.2021.278853. [Epub ahead of print] Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process. Phase I/II TEM/LEN clinical trial Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas Ajay Major1; Justin Kline1; Theodore G.
    [Show full text]
  • Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions
    cancers Review Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions Haneen T. Salah 1 , Courtney D. DiNardo 2 , Marina Konopleva 2 and Joseph D. Khoury 3,* 1 College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; [email protected] 2 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] (C.D.D.); [email protected] (M.K.) 3 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA * Correspondence: [email protected] Simple Summary: Apoptosis dysergulation is vital to oncogenesis. Efforts to mitigate this cancer hallmark have been ongoing for decades, focused mostly on inhibiting BCL-2, a key anti-apoptosis effector. The approval of venetoclax, a selective BCL-2 inhibitor, for clinical use has been a turning point in the field of oncology. While resulting in impressive improvement in objective outcomes, particularly for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and acute myeloid leukemia, the use of venetoclax has exposed a variety of resistance mechanisms to BCL-2 inhibition. As the field continues to move forward, improved understanding of such mechanisms and the potential biomarkers that could be harnessed to optimize patient selection for therapies that include venetoclax and next-generation BCL-2 inhibitors are gaining increased importance. Abstract: Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents Citation: Salah, H.T.; DiNardo, C.D.; targeting this pathway.
    [Show full text]
  • AHRQ Healthcare Horizon Scanning System – Status Update Horizon
    AHRQ Healthcare Horizon Scanning System – Status Update Horizon Scanning Status Update: April 2015 Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. HHSA290-2010-00006-C Prepared by: ECRI Institute 5200 Butler Pike Plymouth Meeting, PA 19462 April 2015 Statement of Funding and Purpose This report incorporates data collected during implementation of the Agency for Healthcare Research and Quality (AHRQ) Healthcare Horizon Scanning System by ECRI Institute under contract to AHRQ, Rockville, MD (Contract No. HHSA290-2010-00006-C). The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. A novel intervention may not appear in this report simply because the System has not yet detected it. The list of novel interventions in the Horizon Scanning Status Update Report will change over time as new information is collected. This should not be construed as either endorsements or rejections of specific interventions. As topics are entered into the System, individual target technology reports are developed for those that appear to be closer to diffusion into practice in the United States. A representative from AHRQ served as a Contracting Officer’s Technical Representative and provided input during the implementation of the horizon scanning system. AHRQ did not directly participate in the horizon scanning, assessing the leads or topics, or provide opinions regarding potential impact of interventions.
    [Show full text]
  • Standard Oncology Criteria C16154-A
    Prior Authorization Criteria Standard Oncology Criteria Policy Number: C16154-A CRITERIA EFFECTIVE DATES: ORIGINAL EFFECTIVE DATE LAST REVIEWED DATE NEXT REVIEW DATE DUE BEFORE 03/2016 12/2/2020 1/26/2022 HCPCS CODING TYPE OF CRITERIA LAST P&T APPROVAL/VERSION N/A RxPA Q1 2021 20210127C16154-A PRODUCTS AFFECTED: See dosage forms DRUG CLASS: Antineoplastic ROUTE OF ADMINISTRATION: Variable per drug PLACE OF SERVICE: Retail Pharmacy, Specialty Pharmacy, Buy and Bill- please refer to specialty pharmacy list by drug AVAILABLE DOSAGE FORMS: Abraxane (paclitaxel protein-bound) Cabometyx (cabozantinib) Erwinaze (asparaginase) Actimmune (interferon gamma-1b) Calquence (acalbrutinib) Erwinia (chrysantemi) Adriamycin (doxorubicin) Campath (alemtuzumab) Ethyol (amifostine) Adrucil (fluorouracil) Camptosar (irinotecan) Etopophos (etoposide phosphate) Afinitor (everolimus) Caprelsa (vandetanib) Evomela (melphalan) Alecensa (alectinib) Casodex (bicalutamide) Fareston (toremifene) Alimta (pemetrexed disodium) Cerubidine (danorubicin) Farydak (panbinostat) Aliqopa (copanlisib) Clolar (clofarabine) Faslodex (fulvestrant) Alkeran (melphalan) Cometriq (cabozantinib) Femara (letrozole) Alunbrig (brigatinib) Copiktra (duvelisib) Firmagon (degarelix) Arimidex (anastrozole) Cosmegen (dactinomycin) Floxuridine Aromasin (exemestane) Cotellic (cobimetinib) Fludara (fludarbine) Arranon (nelarabine) Cyramza (ramucirumab) Folotyn (pralatrexate) Arzerra (ofatumumab) Cytosar-U (cytarabine) Fusilev (levoleucovorin) Asparlas (calaspargase pegol-mknl Cytoxan (cyclophosphamide)
    [Show full text]
  • Highlights in Chronic Lymphocytic Leukemia from the 2019 American Society of Clinical Oncology Annual Meeting
    July 2019 Volume 17, Issue 7, Supplement 11 A SPECIAL MEETING REVIEW EDITION Highlights in Chronic Lymphocytic Leukemia From the 2019 American Society of Clinical Oncology Annual Meeting A Review of Selected Presentations From the 2019 ASCO Annual Meeting • May 31-June 4, 2019 • Chicago, Illinois Special Reporting on: • Final Analysis From RESONATE: Six-Year Follow-Up in Patients With Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma on Ibrutinib • Acalabrutinib With Obinutuzumab in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia: Three-Year Follow-Up • Long-Term Follow-Up of Previously Untreated Patients With Chronic Lymphocytic Leukemia Treated With Ofatumumab and Chlorambucil: Final Analysis of the Phase 3 COMPLEMENT 1 Trial • TRANSCEND CLL 004: Minimal Residual Disease Negative Responses After Lisocabtagene Maraleucel (JCAR017), a CD19-Directed CAR T-Cell Product, in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma • Phase 1/2 Trial of Cirmtuzumab and Ibrutinib: Planned Analysis of Phase 1 CLL Cohorts • Effect of Fixed-Duration Venetoclax Plus Obinutuzumab on Progression-Free Survival, and Rates and Duration of Minimal Residual Disease Negativity in Previously Untreated Patients With Chronic Lymphocytic Leukemia and Comorbidities • Effect of Dose Modifications on Response to Duvelisib in Patients With Relapsed/Refractory CLL/SLL in the DUO Trial • Phase 2 Study of Acalabrutinib in Ibrutinib-Intolerant Patients With Relapsed/Refractory Chronic
    [Show full text]
  • Treating Non-Hodgkin Lymphoma If You’Ve Been Diagnosed with Non-Hodgkin Lymphoma, Your Treatment Team Will Discuss Your Options with You
    cancer.org | 1.800.227.2345 Treating Non-Hodgkin Lymphoma If you’ve been diagnosed with non-Hodgkin lymphoma, your treatment team will discuss your options with you. It’s important to weigh the benefits of each treatment option against the possible risks and side effects. How is non-Hodgkin lymphoma treated? Depending on the type and stage (extent) of the lymphoma and other factors, treatment options for people with NHL might include: ● Chemotherapy for Non-Hodgkin Lymphoma ● Immunotherapy for Non-Hodgkin Lymphoma ● Targeted Drug Therapy for Non-Hodgkin Lymphoma ● Radiation Therapy for Non-Hodgkin Lymphoma ● High-Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin Lymphoma ● Surgery for Non-Hodgkin Lymphoma Common treatment approaches Treatment approaches for NHL depend on the type of cancer, how advanced it is, as well as your health and other factors. Another important part of treatment for many people is palliative or supportive care. This can help prevent or treat problems such as infections, low blood cell counts, or some symptoms caused by the lymphoma. ● Treating B-Cell Non-Hodgkin Lymphoma ● Treating T-Cell Non-Hodgkin Lymphoma ● Treating HIV-Associated Lymphoma 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 ● Palliative and Supportive Care for Non-Hodgkin Lymphoma Who treats non-Hodgkin lymphoma? Based on your treatment options, you may have different types of doctors on your treatment team. These doctors could include: ● A medical oncologist or hematologist: a doctor who treats lymphoma with chemotherapy, immunotherapy, and targeted therapy. ● A radiation oncologist: a doctor who treats cancer with radiation therapy. ● A bone marrow transplant doctor: a doctor who specializes in treating cancer or other diseases with bone marrow or stem cell transplants.
    [Show full text]
  • (CHMP) Agenda for the Meeting on 14-17 September 2020
    14 September 2020 EMA/CHMP/481238/2020 Human Medicines Division Committee for medicinal products for human use (CHMP) Agenda for the meeting on 14-17 September 2020 Chair: Harald Enzmann – Vice-Chair: Bruno Sepodes 14 September 2020, 08:30 – 19:30, room 1C/ virtual meeting 15 September 2020, 08:30 – 19:30, room 1C/ virtual meeting 16 September 2020, 08:30 – 19:30, room 1C/ virtual meeting 17 September 2020, 08:30 – 18:00, room 1C/ virtual meeting Disclaimers Some of the information contained in this agenda is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the CHMP meeting highlights once the procedures are finalised and start of referrals will also be available. Of note, this agenda is a working document primarily designed for CHMP members and the work the Committee undertakes. Note on access to documents Some documents mentioned in the agenda cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on- going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006). Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020.
    [Show full text]
  • Protocol Alert
    14 Protocol Alert New clinical trials recently added to the National Cancer Institute’s database oncology-times.com • BRAIN/CNS TUMORS and Cyclophosphamide in Treating ENDOMETRIAL CANCER Phase: Phase II, Phase I Light Sedation or Intubated Patients with Stage I-III Triple- Levonorgestrel-Releasing Type: Treatment General Anesthesia in Reducing Negative Breast Cancer Intrauterine System with or without Age: 18 and over Complications and Length of Phase: Phase II Everolimus in Treating Patients with Trial IDs: SGN35-016, Hospital Stay in Patients With Brain Type: Treatment Atypical Hyperplasia or Stage IA NCI-2013-00461, NCT01874054 Cancer Undergoing Craniotomy Age: 18 to 70 Grade 1 Endometrial Cancer Phase: Phase IV Trial IDs: 2014-BRST-TNBC-LQT, Phase: Phase II Safety, Tolerability, and Efficacy of October 10, 2015 Type: Supportive care, Treatment NCI-2015-01416, STUDY00002467, Type: Biomarker/Laboratory analysis, TAK-659 in Adults With Relapsed • Age: 19 and over NCT02413320 Treatment or Refractory Acute Myelogenous Trial IDs: OSU-12161, NCI-2014- Age: 18 and over Leukemia (AML) 01110, 2014C0007, NCT02193568 Trial IDs: 2014-0944, Phase: Phase II, Phase I CERVICAL CANCER NCI-2015-00919, NCT02397083 Type: Treatment Pazopanib Hydrochloride and Age: 18 and over BREAST CANCER Topotecan Hydrochloride in Treating Trial IDs: C34002, NCI-2015-00064, Study to Evaluate the Efficacy and Patients with Stage IVB or Recurrent HEAD & NECK/ U1111-1163-2185, NCT02323113 Safety of Eribulin Mesylate in Cervical Cancer ORAL CANCER Combination With Pembrolizumab
    [Show full text]