14 september 2022: Bron: Researchsquare

Uit een kleine experimentele studie met maar 6 patiënten met een klassieke lymfklierkanker blijkt dat de combinatie van autologe stamceltransplantatie  samen met een anti-CD30 CAR-T celbehandeling (chimere antigeenreceptor T-celtherapie) een zeer effectieve behandeling te zijn. Alle 6 deelnemende patiënten hadden minimaal twee recidieven gehad ondanks de chemokuren die zij hadden ondergaan. Zelfs voor patiënten met PET-positieve en chemoresistente ziekte werkte deze combinatiebehandeling. 5 van de 6 deelnemende patiënten bereikten een duurzame complete remissie en 1 patiënt een gedeeltelijke remissie van minimaal 50 procent. Alle 5 patiënten die een complete remissie bereikt hadden leefden nog klinisch kankervrij op 20 maanden toen de studie resultaten werden opgemaakt. En ook de patiënt met een gedeeltelijke remissie leefde nog en de kanker bleef stabiel. 

Waarom is deze studie zo belangrijk?

  • De langetermijnresultaten zijn slecht wanneer patiënten met recidiverend/refractair lymfoom vóór een stamceltransplantatie geen volledige respons op de chemotherapie hebben.
  • In klinische onderzoeken met anti-CD30 CAR T-cellen bij recidiverende/refractaire ziekte, was de totale respons 53% tot 78%, en de mediane progressievrije overleving bleek slechts 6 maanden.
  • De huidige studie suggereert dat het combineren van de twee behandelingen een krachtig synergetisch effect kan hebben, waardoor de overlevingsresultaten ten opzichte van elke behandeling als solo behandeling  kan worden verbeterd.
Studie opzet was deze:

  • Vijf patiënten met een klassiek Hodgkin-lymfoom en één met ALK-negatief anaplastisch grootcellig lymfoom kregen CD34-positieve hematopoëtische stamcellen na myeloablatieve chemotherapie en een anti-CD30 CAR-T-therapie.
  • Drie patiënten hadden minstens twee keer een terugval gehad en drie hadden primaire refractaire ziekte.
  • Voor alle patiënten was de PET-beeldvorming positief vóór transplantatie (Deauville 4-5) dus aantoonbaar lymfklierkanker.

Belangrijkste resultaten

  • Engraftment was in alle gevallen succesvol.
  • Het objectieve responspercentage was 100%, inclusief vijf complete remissies (CR) en één gedeeltelijke remissie (PR).
  • Bij een mediane follow-up van 20,4 maanden waren alle zes de patiënten in leven en bleven ze reageren op de behandeling.
  • Vijf patiënten ontwikkelden het cytokine-afgiftesyndroom, echter allemaal slechts van graad 1.
  • Er werd geen neurotoxiciteit waargenomen.

Beperkingen van het onderzoek:

Het onderzoek was een klein onderzoek door één instelling.
Slechts één patiënt ontving het CD30-gerichte antilichaam-geneesmiddel-conjugaat brentuximab vedotin, dat in China werd goedgekeurd nadat het onderzoek was gestart.



lees ook dit studierapport, abstract onderaan artikel: 

Anti-CD30 chimeric antigen receptor T cell therapy for relapsed/refractory CD30+ lymphoma patients

Het volledige studieverslag van deze studie met de 6 patiënten is gratis in te zien. Klik op de titel van het abstract:

Research Article

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30 + lymphoma

https://doi.org/10.21203/rs.3.rs-1963480/v1

This work is licensed under a CC BY 4.0 License

Methods: This open-label, single-center and single-arm pilot study investigated the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30+ lymphoma. The primary endpoint was safety and key secondary endpoint was overall response rate, overall survival, progression-free survival, and duration of response.

Results: Five classical Hodgkin lymphoma (cHL) patients and 1 anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) patient were enrolled. The median age was 24 years. No patient had prior ASCT. Three patients (50.0%) relapsed for ≥ 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) at enrollment. All patients received myeloablative chemotherapy and infused CD34-positive hematopoietic stem cells (HSCs) and CAR30 T cells in tandem, with a median dose of 3.9 ×106/kg and 7.6 ×106/kg, respectively. Five paitents presented with cytokine release syndrome (CRS), all of which were grade 1. No neurotoxicity was observed. All patients had successful HSCs engraftment and reached an objective response, including 5 (4 cHL and 1 ALCL, 83.3%) with a complete response (CR) and 1 with a partial response (PR). With a median follow-up of 20.4 (range, 12.1-34.4) months, all remained alive and maintained their responses.

Conclusion: Our work demonstrates the combined administration of ASCT and CAR30 T-cell therapy is well-tolerate and highly effective in r/r cHL and ALCL, even in PET-positive or chemorefractory patients who are expected to have inferior outcome after ASCT, although further large-scaled validation in prospective clinical trial is warranted.

Trial registration: The trial was registered with the Chinese Clinical Trial Registry (ChiCTR, number ChiCTR2100053662).


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Anti-CD30 chimeric antigen receptor T cell therapy for relapsed/refractory CD30+ lymphoma patients

Blood Cancer Journal volume 10, Article number: 8 (2020) Cite this article  

figure 1

a The serum IL-6 level of each patient was assessed before and at serial time points after cell infusion; the red lines representing the three patients with higher tumor burden were much higher than the others. b The serum ferritin level of each patient was assessed before and at serial time points after cell infusion; the red lines representing the three patients with higher tumor burden were much higher than the others. c The copies of anti-CD30 CAR transgenes, the red lines representing the five patients who received anti-PD-1 antibody last longer; the horizontal line denotes the lower limit of quantitation (50 copies/μg). d Clinical responses for the nine patients. On the left of the Y axis is the disease status before infusion; arrows indicate alive; the star marker indicated the start time of anti-PD-1 antibody therapy. Patient #5 received autologous transplantation 4 months after PD, and achieved CR again (CR2). e Progression-free survival of all nine patients. NA not applicable, PD progression of disease, SD stable disease, PR partial response, CR complete response.

lymfklierkanker, Autologe stamceltransplantatie, anti-CD30 CAR-T celtherapie, complete remissies


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