Successful treatment of relapsed Waldenström’s macroglobulinemia with proteasome inhibitors (bortezomib and subsequently ixazomib) in combination with rituximab and dexamethasone. A case report and review of the of proteasome inhibitors in Waldenström’s macroglobulinemia
Authors:
Z. Adam 1; M. Krejčí 1; L. Pour 1; B. Weinbergerová 1; V. Sandecká 1; M. Štork 1; I. Boichuk 1; Z. Řehák 2; M. Keřkovský 3; R. Koukalová 2; L. Zdražilová-Dubská 4,5; B. Čechová 3; Z. Král 1
Authors place of work:
Interní hematologická a onkologická klinika LF MU a FN Brno
1; Oddělení nukleární medicíny, MOU Brno
2; Klinika radiologie a nukleární medicíny LF MU a FN Brno
3; Ústav laboratorní medicíny LF MU a FN Brno
4; Katedra laboratorních metod a CREATIC, LF MU Brno
5
Published in the journal:
Klin Onkol 2024; 39(6): 451-462
Category:
Case Reports
doi:
https://doi.org/10.48095/ccko2024451
Summary
Background: Waldenström’s macroglobulinemia (WM) is a very rare disease with an incidence 10times lower than that of multiple myeloma. The incidence of WM is also significantly lower than that of the other CD20+ low-grade lymphomas. The rarity of WM is the reason why registration studies of new drugs used for multiple myeloma or the more common CD20+low-grade lymphomas do not cover WM. Data on the efficacy of proteasome inhibitors in WM can be drawn from case descriptions, small series of patients and a few phase II clinical trials. The aim of this case report and review is to inform about our experience with the treatment of WM with bortezomib and then ixazomib and to present an overview of publications on proteasome inhibitors in WM. Case: We describe a patient who, after 8 years of asymptomatic course of WM, had the first fulminant progression with severe pancytopenia at the age of 74 years. For the first-line treatment, he was treated with dexamethasone and rituximab, and after alleviation of pancytopenia, with bendamustine. Monoclonal immunoglobulin IgM (M-IgM) dropped from 40 g/L to the level as low as 6.9 g/L, which meant partial remission (PR) accompanied with normal blood count values. After 29 months of PR, the patient experienced a fulminant relapse of WM, accompanied by severe pancytopenia. Rituximab and dexamethasone were the backbone of treatment with addition of bortezomib for its significantly lower myelosuppression compared to alkylating agents. Treatment with the triple combination of bortezomib, rituximab, and dexamethasone was effective, however, after five cycles, bortezomib had to be discontinued for severe neurotoxicity. The sixth cycle contained rituximab and dexamethasone, and from the seventh cycle, ixazomib was started. The patient underwent seven cycles (months) of treatment consisting of ixazomib, rituximab and dexamethasone (14 cycles of treatment in total). Results: M-IgM decreased from 30 g/L at the beginning of the treatment to 4.0 g/L at the end of treatment and further decreased to a value of 2.8 g/L at the eighth month after the end of the treatment. A deeper decrease in M-IgM than after first-line treatment was achieved and the patient now meets the criteria for a very good partial remission. Conclusion: According to the described experience and according to the review of publications evaluating proteasome inhibitors in WM, the combination of ixazomib with rituximab and dexamethasone excels with very good tolerance and high efficacy, approaching the efficacy of the combination of rituximab with bendamustine. This combination has its place particularly in patients with WM and cytopenia.
Keywords:
bortezomib – Waldenström’s macroglobulinemia – ixazomib
Zdroje
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