Blinatumomab, een nieuw gericht middel voor kankercellen met CD-19 expressie, zorgt in fase II studie bij 9 van de 12 deelnemers met uitbehandelde vergevorderde ALL, voor complete remissie.

28 april 2023:

Zie ook dit artikel: https://kanker-actueel.nl/blinatumomab-geeft-hele-goede-resultaten-bij-babys-met-acute-lymfatische-leukemie-93-vs-66-procent-op-2-jaars-meting-bewijst-nederlands-onderzoek.html

27 november 2018: lees ook dit artikel:

https://kanker-actueel.nl/blinatumomab-bij-een-recidief-of-ziekteprogressie-van-all-acute-lymfatische-leukemie-blijkt-uitstekend-medicijn-bij-zowel-kinderen-als-volwassenen-blijkt-uit-reviewstudie.html

2 februari 2015: lees ook dit artikel:

blinatumomab-blincyto-geeft-volledige-minimale-zogeheten-residuele-ziekte-bij-80-procent-van-de-patienten-met-all-acute-lymfatische-leukemia-en-kan-all-genezen

1 april 2013: zie ook receptor-gemodificeerde-t-cellen-leiden-tot-totale-remissies-bij-uitbehandelde-agressieve-acute-lymfatische-leukemie-all-en-geven-hoop-op-genezende-behandeling die zelfde aanpak beschrijft als onderstaande aanpak

20 juni 2011: Bron: 16th Congress of the European Hematology Association (EHA) via Medscape

Eindelijk lijkt er hoop voor kinderen en volwassenen met een steeds terugkerende en gevorderde vorm van acute lymfatische leukemie. Duitse onderzoekers presenteerden op de EHA de resultaten van een kleinschalig onderzoek met blinatumomab. Van de 12 patienten die meededen aan dit onderzoek bleken er 9 een complete remissie te bereiken. In een eerdere studie bleken 16 van de 20 deelnemende patienten een complete remissie te bereiken. En 60% daarvan was na 27 maanden nog steeds ziektevrij. Dat is wel bijzonder, ook omdat alle deelnemende patienten al eerdere behandelingen als stamceltransplantatie en verschillende chemokuren achter de rug hadden en desondanks weer een recidief kregen. En in feite er geen andere behandelopties meer voor hun waren. Blinatumomab is een zogeheten gericht medicijn. Het werkt op kankercellen die veel eiwitten hebben met CD-19 expressie. Bepaalde leukemiecellen (B-cell-derived) en ook non-Hodgkin lymphomen hebben meestal zo'n eiwit met CD-19 expressie, zeggen de onderzoekers. Hier enkele citaten uit een artikel in Medscape dat als u hier klikt volledig kunt lezen.

Blinatumomab, an investigational drug from a novel class known as BiTE antibodies, resulted in complete remission (CR) or complete remission with only partial hematologic recovery (CR+) in 9 of 12 patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) in a small study.

Bron: Medscape

Dismal Prognosis for Relapsed/Refractory ALL

Blinatumomab is the first of a new class of agents designed to direct cytotoxic T-cells to CD19-expressing cancer cells. CD19 is a protein expressed on the surface of B-cell-derived ALLs and non-Hodgkin's lymphomas.

According to Dr. Topp, patients with refractory ALL have a dismal prognosis. Complete remission rates in this subset range from 17% to 45% with intensive chemotherapy, and treatment-related mortality rates range from 12% to 23%. "Even with the best chemotherapy currently available for these patients, such as FLAG/IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin], only 30% of patients will go into remission. Remission is then usually only of short duration, with a median of around 6 months," he explained.

In the current study, patients had difficult-to-treat B-precursor ALL, and all had relapsed after induction and consolidation therapy once or twice, or had refractory disease. The majority of patients had undergone allogeneic stem cell transplantation in addition to other chemotherapy.

After receiving blinatumomab, 9 of 12 patients reached the primary end point of CR or CR+; all 9 also reached the secondary end point of becoming MRD-negative or obtained molecular remission. Both CR and MRD were reached within the first cycle in responders, so it is "a precise and quick therapy," said Dr. Topp.

"This is unusual in this particular patient group," he remarked.

"This means there was a reduction in tumor burden of greater than 5 logs. This is very significant because the CR rate means a reduction of 1 log, but molecular remission equates to a reduction of 5 logs of tumor burden," he added.

The duration of response remains unknown in this particular trial, and will be reported at a later date, Dr. Topp noted. However, he cited a study he was involved with that was published online May 16 in the Journal of Clinical Oncology, which investigated the effect of blinatumomab on MRD and duration of response. "We found patients who are still MRD-negative after 2.5 years. Extrapolating from those data to this trial, there may be patients who experience a very similar clinical course," said Dr. Topp

Various Dose Regimens

In the current study, there are 4 cohorts; interim data were presented for 2 of these. Patients in the first cohort received blinatumomab 15 mg as continuous infusion for 28 days in cycles 1, 2, 3, and 4. Five of 7 patients responded with CR or CR+.

In the second cohort, in the first week of cycle 1, patients received a lead-in phase of blinatumomab 5 μg/m² per 24 hours; this was escalated to 15 μg/m² per 24 hours for the remainder of cycle 1, and for cycles 2, 3, and 4.

"Remarkably, with this gradual dose escalation, there were no adverse events, yet we found the same CR rate as the first cohort. This is really very important," Dr. Topp emphasized. Read more>>>>>

Shifra, immuuntherapie, CD19, acute lymfatische leukemie, ALL, leukemie, blinatumomab