Lees ook het verhaal van Antoon die al in 1994 de diagnose ziekte van Waldenström kreeg. Antoon leeft nog steeds en heeft net zijn tweede chemokuur achter de rug. Maar voelt zich best goed en is nog steeds actief.

Of het verhaal van Loes die enkele jaren geleden weliswaar is overleden maar heel lang heeft geleefd met de ziekte van Waldenström

15 oktober 2021: Bron: Journal of Clinical Oncology Published online October 04, 2021.

Bij patiënten met de ziekte van Waldenström blijkt een behandeling van ibrutinib plus rituximab (MabThera) voor veel betere resultaten te zorgen in vergelijking met rituximab plus een placebo wat betreft ziekteprogressie vrije tijd en naar te verwachten ook op de overall overleving. Want na 50 maanden follow-up van de fase III iNNOVATE studie (75 vs 75 patiënten) blijkt het verschil in ziekteprogressie vrije tijd maar liefst meer dan verdubbeld. In de ibrutinib plus rituximabgroep was de ziekteprogressie vrije tijd 57,9 maanden en mediaan nog niet bereikt tegenover mediaan 20,3 maanden (range: 13.0 to 27.6 maanden) in de placebo-rituximab groep (hazard ratio, 0.250; P < .0001).

Bij symptomatische patiënten waren de respons percentages en progressievrije overleving verbeterd met ibrutinib plus rituximab versus alleen ibrutinib. Deze betere resultaten traden op ongeacht eerdere behandelingen, mutatiestatus of subgroep gedefinieerd door IgM-niveau, hemoglobine, IPSS en MYD88-mutatiestatus en CXCR4 mutatiestatus.

Resultaten:

Hogere responspercentages (gedeeltelijke respons = PR of beter) werden waargenomen met ibrutinib-rituximab (76% versus 31% met placebo-rituximab; P <.0001) en hielden aan in de tijd.
De mediane tijd tot de volgende behandeling werd niet bereikt met ibrutinib-rituximab versus 18 maanden met placebo-rituximab.
Meer patiënten die ibrutinib-rituximab kregen versus placebo-rituximab hadden een aanhoudende verbetering van de hemoglobine (77% versus 43%; P <.0001).
De mediane totale overleving werd in geen van beide groepen bereikt. Ibrutinib-rituximab toonde een beheersbaar veiligheidsprofiel; de prevalentie van graad ≥ 3 bijwerkingen van klinisch belang nam in het algemeen af in de loop van de tijd.

FIG 1.PFS (A) in the intention-to-treat population, (B) by genotype, and (C) by prior treatment status. For PFS by genotype and prior treatment status, Kaplan-Meier curves are shown for time points with ≥ 10 patients. HR, hazard ratio; NR, not reported; PFS, progression-free survival.

De onderzoekers van de fase III iNNOVATE studie stellen dan ook dat de combinatiebehandeling ibrutinib plus rituximab standaardbehandeling moet worden.

Conclusie: In de uiteindelijke analyse van iNNOVATE met een mediane follow-up van 50 maanden, vertoonde ibrutinib-rituximab aanhoudende superioriteit over klinische uitkomsten bij patiënten met ziekte van Waldenström (WM), ongeacht de MYD88- of CXCR4-mutatiestatus, eerdere behandeling en belangrijke patiëntkenmerken.

Het volledige studierapport is gratis in te zien of te downloaden. Klik daarvoor op de titel van het abstract:

DOI: 10.1200/JCO.21.00838 Journal of Clinical Oncology

Published online October 04, 2021.

Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study

Christian Buske

, MD1 ; Alessandra Tedeschi, MD2; Judith Trotman

, MBChB3; Ramón García-Sanz

, MD, PhD4; David MacDonald

, MD5; Veronique Leblond, MD, PhD6; ...Show More

Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

ABSTRACT

PURPOSE

The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE.

METHODS

Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety.

RESULTS

With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P < .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P < .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P < .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade ≥ 3 adverse events of clinical interest generally decreased over time.

CONCLUSION

In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.

REFERENCES

1.	Imbruvica (ibrutinib) [prescribing information]. Sunnyvale, CA: Pharmacyclics LLC, an AbbVie Company, 2020 Google Scholar
2.	Dimopoulos MA, Tedeschi A, Trotman J, et al: Phase 3 trial of ibrutinib plus rituximab in Waldenström's macroglobulinemia. N Engl J Med 378:2399-2410, 2018 Crossref, Medline, Google Scholar
3.	Dimopoulos MA, Trotman J, Tedeschi A, et al: Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): An open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol 18:241-250, 2017 Crossref, Medline, Google Scholar
4.	Treon SP, Gustine J, Meid K, et al: Ibrutinib monotherapy in symptomatic, treatment-naive patients with Waldenström macroglobulinemia. J Clin Oncol 36:2755-2761, 2018 Link, Google Scholar
5.	National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology. Waldenstrom Macroglobulinia Lymphoplasmatic Lymphoma. Version 1.2021. Plymouth Meeting, PA, National Comprehensive Cancer Network, 2020 Google Scholar
6.	Castillo JJ, Advani RH, Branagan AR, et al: Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. Lancet Haematol 7:e827-e837, 2020 Crossref, Medline, Google Scholar
7.	Hunter ZR, Xu L, Yang G, et al: The genomic landscape of Waldenström macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood 123:1637-1646, 2014 Crossref, Medline, Google Scholar
8.	Treon SP, Cao Y, Xu L, et al: Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenström macroglobulinemia. Blood 123:2791-2796, 2014 Crossref, Medline, Google Scholar
9.	Yang G, Zhou Y, Liu X, et al: A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. Blood 122:1222-1232, 2013 Crossref, Medline, Google Scholar
10.	Treon SP, Meid K, Gustine J, et al: Long-term follow-up of ibrutinib monotherapy in symptomatic, previously treated patients with Waldenström macroglobulinemia. J Clin Oncol 39:565-575, 2020 Link, Google Scholar
11.	Owen RG, Kyle RA, Stone MJ, et al: Response assessment in Waldenström macroglobulinaemia: Update from the VIth International Workshop. Br J Haematol 160:171-176, 2013 Crossref, Medline, Google Scholar
12.	Latimer NR, Abrams KR, Lambert PC, et al: Adjusting survival time estimates to account for treatment switching in randomized controlled trials – an economic evaluation context: Methods, limitations, and recommendations. Med Decis Making 34:387-402, 2014 Crossref, Medline, Google Scholar
13.	Buske C, Tedeschi A, Trotman J, et al: Ibrutinib treatment in Waldenström's macroglobulinemia: Follow-up efficacy and safety from the iNNOVATE study. Poster presented at the 60th American Society of Hematology Annual Meeting and Exposition, San Diego, CA, December 1-4, 2018 Google Scholar
14.	Burger JA, Barr PM, Robak T, et al: Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia 34:787-798, 2020 Crossref, Medline, Google Scholar
15.	Coutre SE, Byrd JC, Hillmen P, et al: Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. Blood Adv 3:1799-1807, 2019 Crossref, Medline, Google Scholar
16.	O'Brien S, Furman RR, Coutre S, et al: Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: A 5-year experience. Blood 131:1910-1919, 2018 Crossref, Medline, Google Scholar
17.	Gustine JN, Meid K, Dubeau T, et al: Ibrutinib discontinuation in Waldenström macroglobulinemia: Etiologies, outcomes, and IgM rebound. Am J Hematol 93:511-517, 2018 Crossref, Medline, Google Scholar
18.	Treon SP, Gustine J, Xu L, et al: MYD88 wild-type Waldenström macroglobulinaemia: Differential diagnosis, risk of histological transformation, and overall survival. Br J Haematol 180:374-380, 2018 Crossref, Medline, Google Scholar
19.	Tam CS, Opat S, D'Sa S, et al: A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: The ASPEN study. Blood 136:2038-2050, 2020 Crossref, Medline, Google Scholar
20.	Treon SP, Xu L, Guerrera ML, et al: Genomic landscape of Waldenström macroglobulinemia and its impact on treatment strategies. J Clin Oncol 38:1198-1208, 2020 Link, Google Scholar
21.	Trotman J, Buske C, Tedeschi A, et al: Long-term follow-up of ibrutinib treatment for rituximab-refractory Waldenström's macroglobulinemia: Final analysis of the open-label substudy of the phase 3 iNNOVATE™ trial. Blood 136:38-39, 2020 Crossref, Google Scholar