Raadpleeg ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij leukemie van arts-bioloog drs. Engelbert Valstar. 

10 december 2018: Bron: NEJM 1 december 2018

Ibrutinib als monobehandeling bij oudere patienten (ouder dan 65 jaar) met nieuwe diagnose van Chronische Lymfatische Leukemie geeft veel betere resultaten op progressievrije ziekte dan de combinatiebehandeling bendastumine plus rituximab die nu standaardbehandeling is.

Opvallend is dat ook uit de studie blijkt dat wanneer ibrutinib alleen gecombineerd wordt met rituximab er min of meer gelijke resultaten waren in de progressievrije ziekte. Terwijl gecombineerd met bendastumine erbij ibrutinib dus ook betere resultaten gaf. ((87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval , 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001))

Afbeeldingsresultaat voor image of ibrutinibSource: Imbruvica.com

Wat dan wel weer opvalt is dat ondanks de hogere algemene respons (bepaald door CT en lichamelijk onderzoek) in de ibrutinib-groepen (93% versus 81%), een volledige remissie (CR) werd bereikt bij slechts 7% in de ibrutinibgroep, vergeleken met 26% in de bendatumine / rituximabgroep. Dat zou verklaard kunnen worden door het feit dat bendustamine / rituxiomab slechts 6 kuren werd gegeven en ibrutinib als onderhoudsbehandeling mediaan 32 maanden lang werd gegeven.

Slechts een klein aantal patiënten bereikte een niet-detecteerbare ziekte (MRD): 1% in de benda / ritux-groep en 4% tot 8% in de ibrutinib-groepen. De onderzokers stellen zich dan ook de vraag of rituximab iets toevoegt aan ibrutinib in onbehandelde CLL en of en hoe een hogere mate van niet detecterbare ziekte  (MRD) kan worden bereikt, met het gegeven dat patiënten ibrutinib niet voor onbepaalde tijd zouden hoeven te nemen.

Ibrutinib geeft ondanks de veel langere tijd van behandelen wel minder bijwerkingen dan bendastumine / rituximab.  

De patienten (allemaal ouder dan 65 jaar met nieuwe diagnsoe van Chronische Lymfatische Leukemie (CLL) waren gerandomiseerd ingedeeld in drie groepen: of bendamustine plus rituximab (n=183), ibrutinib alleen (n=182), of ibrutinib met rituximab (n=182). Met dus zoals hierboven aangegeven het resultaat dat ibrutinib er als beste uitkwam wat betreft progressievrije ziekte. 

Conclusie van de onderzoekers luidt:

Bij oudere patiënten met onbehandelde CLL was de behandeling met ibrutinib superieur aan de behandeling met bendamustine plus rituximab met betrekking tot progressievrije overleving. Er was geen significant verschil tussen ibrutinib en ibrutinib plus rituximab met betrekking tot progressievrije overleving. (De studie is gefinancierd door het National Cancer Institute and Pharmacyclics; ClinicalTrials. gov number, NCT01886872.)

Het studierapport: Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL is tegen betaling in te zien.

Hier het abstract van de studie: 

Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. There was no significant difference between ibrutinib and ibrutinib plus rituximab with regard to progression-free survival.

Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL

  • Jennifer A. Woyach, M.D.,
  • Amy S. Ruppert, Ph.D.,
  • Nyla A. Heerema, Ph.D.,
  • Weiqiang Zhao, M.D.,
  • Allison M. Booth, M.S.,
  • Wei Ding, M.B., B.S., Ph.D.,
  • Nancy L. Bartlett, M.D.,
  • Danielle M. Brander, M.D.,
  • Paul M. Barr, M.D.,
  • Kerry A. Rogers, M.D.,
  • Sameer A. Parikh, M.B., B.S.,
  • Steven Coutre, M.D.,
  • Arti Hurria, M.D.,
  • Jennifer R. Brown, M.D., Ph.D.,
  • Gerard Lozanski, M.D.,
  • James S. Blachly, M.D.,
  • Hatice G. Ozer, Ph.D.,
  • Brittny Major-Elechi, M.S.,
  • Briant Fruth, B.S.,
  • Sreenivasa Nattam, M.D.,
  • Richard A. Larson, M.D.,
  • Harry Erba, M.D., Ph.D.,
  • Mark Litzow, M.D.,
  • Carolyn Owen, M.D., Ph.D.,
  • Charles Kuzma, M.D.,
  • Jeremy S. Abramson, M.D.,
  • Richard F. Little, M.D.,
  • Scott E. Smith, M.D., Ph.D.,
  • Richard M. Stone, M.D.,
  • Sumithra J. Mandrekar, Ph.D.,
  • and John C. Byrd, M.D.

Abstract

Background

Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy.

Methods

Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met.

Results

A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval , 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001). There was no significant difference between the ibrutinib-plus-rituximab group and the ibrutinib group with regard to progression-free survival (hazard ratio, 1.00; 95% CI, 0.62 to 1.62; P=0.49). With a median follow-up of 38 months, there was no significant difference among the three treatment groups with regard to overall survival. The rate of grade 3, 4, or 5 hematologic adverse events was higher with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen).

Conclusions

Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. There was no significant difference between ibrutinib and ibrutinib plus rituximab with regard to progression-free survival. (Funded by the National Cancer Institute and Pharmacyclics; ClinicalTrials.gov number, NCT01886872.)

Supported by the following awards from the National Cancer Institute (NCI) of the National Institutes of Health: U10CA180821 and U10CA180882, to the Alliance for Clinical Trials in Oncology (Alliance); UG1CA189823, to the Alliance NCI Community Oncology Research Program Research Base; U10CA180790, U10CA180833, U10CA180836, U10CA180850, U10CA180857, U10CA180867, P30CA033572, UG1CA189858, U10CA180820, U10CA180790, and U10CA180888, to the Eastern Cooperative Oncology Group and Southwest Oncology Group; K23CA178183, to Dr. Woyach; R01CA197870, to Drs. Woyach and Byrd; and R35CA197734, to Dr. Byrd. The trial was supported in part by Pharmacyclics (a subsidiary of AbbVie).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

This article was published on December 1, 2018, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank Susan Geyer, Ph.D., for assistance with the initial trial design; Samantha Sublett, Eva Hoke, and Luke Wilson for assistance with the protocol and data management; and Neil Kay and Tait Shanafelt for assistance with the conception and design of the trial.

Author Affiliations

From Ohio State University Comprehensive Cancer Center, Columbus (J.A.W., A.S.R., N.A.H., W.Z., K.A.R., G.L., J.S.B., H.G.O., J.C.B.); the Alliance Statistics and Data Center (A.S.R., A.M.B., B.M.-E., B.F., S.J.M.), Mayo Clinic (W.D., S.A.P., M.L.), Rochester, MN; Washington University School of Medicine, St. Louis (N.L.B.); Duke Cancer Institute, Duke University Medical Center, Durham (D.M.B., H.E.), and First Health of the Carolinas Cancer Center, Pinehurst (C.K.) — both in North Carolina; the University of Rochester Medical Center, Rochester, NY (P.M.B.); Stanford University School of Medicine, Stanford (S.C.), and the City of Hope Comprehensive Cancer Center, Duarte (A.H.) — both in California; Dana–Farber Partners CancerCare (J.R.B., R.M.S.) and the Massachusetts General Hospital Cancer Center (J.S.A.) — both in Boston; Fort Wayne Medical Oncology and Hematology, Fort Wayne, IN (S.N.); University of Chicago Comprehensive Cancer Center (R.A.L.) and Loyola University Chicago (S.E.S.) — both in Chicago; the University of Calgary, Tom Baker Cancer Centre, Calgary, AB, Canada (C.O.); and the Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD (R.F.L.).

Address reprint requests to Dr. Woyach at the Division of Hematology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH 43212, or at .

Arti Hurria, M.D., is deceased.


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