9 mei 2017: lees ook dit artikel: 

https://kanker-actueel.nl/NL/pembrolizumab-immuuntherapie-met-een-anti-pd-medicijn-geeft-uitstekende-resultaten-bij-recidief-of-progressie-van-voorbehandelde-patienten-met-lymfklierkanker-non-hodgkin.html

2 december 2016: Lees ook dit artikel: 

https://kanker-actueel.nl/NL/immuuntherapie-met-extra-gemoduleerde-t-car-cells-geeft-bij-zwaar-voorbehandelde-lymfklierkanker-non-hodgkin-alsnog-uitstekende-resultaten-met-33-procent-complete-remissies.html

2 december 2016: De FDA heeft per 1 december 2016 verdere goedkeuring gegeven aan verder onderzoek naar pembrolizumab (Keytruda) bij klassieke vormen van lymfklierkanker. Zo meldt producent Merck op hun website:

............ the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with refractory classical Hodgkin lymphoma (cHL) or for patients who have relapsed after three or more prior lines of therapy. ..............

“Patients with refractory or relapsed classical Hodgkin lymphoma have limited treatment options,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We believe that the expedited review of this sBLA granted by the FDA is an important step in helping us make KEYTRUDA available as quickly as possible to patients living with this disease.”

The application is seeking approval for KEYTRUDA at a fixed dose of 200 mg administered intravenously every three weeks and is based on data from the KEYNOTE-087 and KEYNOTE-013 trials, which studied patients with refractory cHL or who had relapsed after three or more prior lines of therapy. This is the first application for regulatory approval of KEYTRUDA in a hematologic malignancy.

......lees meer>>>>>>>>

Artikel gaat verder onder deze grafiek

pembrolizumab bij lymfklierkanker

Een interessante reviewstudie over anti-PDF medicijnen bij klassieke lymfklierkanker is deze studie: 

Pembrolizumab in classical Hodgkin’s lymphoma

met interessanter referentielijst die ik onderaan dit artikel heb gepubliceerd. Scroll ook verder voor meer over pembrolizumab bij klassieke lymfklierkanker

Mocht u kanker-actueel de moeite waard vinden en ons willen ondersteunen om kanker-actueel online te houden dan kunt u ons machtigen voor een periodieke donatie via donaties: https://kanker-actueel.nl/NL/donaties.html of doneer al of niet anoniem op - rekeningnummer NL79 RABO 0372931138 t.n.v. Stichting Gezondheid Actueel in Amersfoort. Onze IBANcode is NL79 RABO 0372 9311 38   
 Elk bedrag is welkom. En we zijn een ANBI instelling dus uw donatie of gift is in principe aftrekbaar voor de belasting.

En als donateur kunt u ook korting krijgen bij verschillende bedrijven: 

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16 juli 2016: Bron: Published online before print June 27, 2016, doi: 10.1200/JCO.2016.67.3467 JCO JCO673467

Immuuntherapie met pebrozilumab geeft zeer goede resultaten bij zwaarvoorbehandelde patiënten met een klassieke vorm van lymfklierkanker (ziekte van Hodgkin). Van alle deelnemende patienten aan deze veiligheidsstudie (N = 31) had 55% minimaal 4 chemokuren met bv. Brentuximab - Vendotin achter de rug en 71% een stamceltransplantatie maar desondanks toch een recidief.

Uit deze studie met pebrolizumab blijkt dat maar liefst 65% goed reageerde op de anti-PD medicijnen en zelfs 5 patienten (16%) bereikten alsnog een totale remissie = klinisch kankervrij.

Opnieuw het bewijs dat immuuntherapie met een anti-PD medicijn al of niet gecombineerd met bv. T-cell stimulatie voor nagenoeg alle vormen van kanker met solide tumoren de beste aanpak lijkt, zeker als eerdere behandelingen hebben gefaald.

En ik blijf het herhalen: wat zou immuuntherapie met bv. deze anti-PD medicijnen opleveren bij eerste diagnose? Zouden dan ook de bijwerkingen optreden die nu optreden omdat mensen vaak nog een pittige tumorload hebben of verzwakte lichamelijke conditie enz.?

Klik voor een uitstekend gedocumenteerd studierapport naar optredende bijwerkingen bij immuuntherapie met anti-PD medicijnen op het volgende Word document. Immuuntherapie met anti-PD en de bijwerkingen

immuuntherapie en bijwekringen van anti-PD medicijnen

Studieresultaten:

Aan de studie namen deel 31 patiënten met een recidief of progressie van lymfklierkanker (ziekte van Hodgkin) tijdens of na een behandeling met brentuximab vedotin. Alle patiënten kregen pembrolizumab met een dosis van 10 mg/kg elke twee weken tot zich progressie van de ziekte voordeed of niet meer te dragen bijwerkingen.  Overall, 55% van de patiënten had ten minste vier chemokuren gehad en 71% had een recidief gekregen na een autologe stamceltransplantatie.

Bijwerkingen:

De meest voorkomende bijwerkingen gerelateerd aan de behandeling waren: schildklierproblemen hypothyroidism (16%), diarree (16%), misselijkheid (13%), en lichte longontstekingen - pneumonitis (10%).
Graad 3 bijwerkingen gerelateerd aan de behandeling kwamen voor bij 5 patiënten(16%) en bestond uit colitis, verhoogde leverwaarden - ALAT - alanine transaminase en ASAT - aspartate transaminase, nephrotic - niersyndroom, opgezwollen en pijnlijke gewrichten, rugpijn en okselpijn.

Er waren geen graad 4 bijwerkingen en ook overleden er geen mensen tijdens of aan de behandeling. Twee patiënten onderbraken de behandeling tijdens de studieduur wegens een graad 2 longontsteking en graad 3 niersyndroom.

Respons en klinische resultaten:

Bij 20 patiënten (65%), werd een goede respons gezien waaronder een complete remissie bij 5 patiënten (16%). De respons duurde minimaal 24 weken bij 70 procent van de patiënten die een respons lieten zien. Na een mediane follow-up van 17 maanden varieerde de duur van de respons van 0.14+ weken tot 74+ weken. Progressie-vrije overleving was 69% op 24 weken en 46% op 1 jaar.

Hoge expressie van de PD-L1 (programmed cell death ligand 1) en PD-L2 (programmed cell death ligand 2); uitbreiding van door de behandeling veroorzaakte T cellen en natural killer cellen; en activatie van interferon-γ, T-cell receptor en uitbreidende immuun gerelateerde zogeheten 'signaling pathways' werden gezien in een biomarker analyse.

Conclusie:

De onderzoekers concluderen: “Pembrolizumab wordt geassocieerd aan een goed veiligheidsprofiel. Een behandeling met Pembrolizumab veroorzaakte uitstekende klinische resultaten bij patienten met zwaarvoorbehandelde lymfklierkanker - ziekte van Hodgkin en verdere studies worden aanbevolen."

Het volledige studierapport: Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure is gratis in te zien.

Hier ook het abstract van deze studie:

pembrolizumab (Keytruda) is active in patients with disease progressing on or after brentuximab vedotin (Adcetris) treatment and gives even 16 procent complete remissions in heavily pretreated patients with relapsed or refractory Hodgkin lymphoma

Published online before print June 27, 2016, doi: 10.1200/JCO.2016.67.3467 JCO JCO673467

2016 by American Society of Clinical Oncology

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure

  1. Craig H. Moskowitz⇑

+ Author Affiliations

  1. Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; Pier Luigi Zinzani, Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY.
  1. Corresponding author: Craig H. Moskowitz, MD, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: moskowic@mskcc.org.

  1. Presented at the American Society of Hematology 56th Annual Meeting and Exposition, San Francisco, CA, December 6-9, 2014; and American Society of Hematology 57th Annual Meeting and Exposition, Orlando, FL, December 5-8, 2015.

 
Next Section

Abstract

Purpose Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations leading to overexpression of the programmed death-1 (PD-1) ligands, suggesting a possible vulnerability to PD-1 blockade. The phase Ib study KEYNOTE-013 (NCT01953692) tested the safety and efficacy of the anti–PD-1 antibody pembrolizumab in patients with hematologic malignancies. Based on its genetics, HL was included as an independent cohort.

Methods We enrolled patients with relapsed or refractory HL whose disease progressed on or after treatment with brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, until disease progression occurred. Response to treatment was assessed at week 12 and every 8 weeks thereafter. Principal end points were safety and complete remission (CR) rate.

Results Thirty-one patients were enrolled; 55% had more than four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation. Five patients (16%) experienced grade 3 drug-related adverse events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR rate was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial remission, for an overall response rate of 65% (90% CI, 48% to 79%). Most of the responses (70%) lasted longer than 24 weeks (range, 0.14+ to 74+ weeks), with a median follow-up of 17 months. The progression-free survival rate was 69% at 24 weeks and 46% at 52 weeks. Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-γ, T-cell receptor, and expanded immune-related signaling pathways.

Conclusions Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.

referentielijst bij pembrolizumab bij lymfklierkanker

Source: 

Eur J Haematol. Author manuscript; available in PMC 2016 Sep 1.
Published in final edited form as:
PMCID: PMC4987237
NIHMSID: NIHMS805054

Pembrolizumab in classical Hodgkin’s lymphoma

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lymfklierkanker, melanomen, non-Hodgkin, immuuntherapie, klinisch kankervrij, Bernhard van Vollenhoven, anti-PD medicijnen, immuuntherpaie, pebrolizumab


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