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CHRONIC LYMPHOCYTIC LEUKEMIA

Ibrutinib in combination with rituximab is highly effective in treatment of chronic lymphocytic leukemia patients with steroid refractory and relapsed autoimmune cytopenias

Leukemia volume 37, pages 1464–1473 (2023)Cite this article

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Abstract

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are common complications of CLL. The optimal treatment of steroid refractory AIHA/PRCA is not well established. We conducted a multicenter study of ibrutinib and rituximab in patients with relapsed/refractory to steroids AIHA/PRCA and underlying CLL. Protocol included induction (ibrutinib 420 mg/day and rituximab, 8 weekly and 4 monthly infusions) and maintenance phase with ibrutinib alone until progression or unacceptable toxicity. Fifty patients were recruited (44—warm AIHA, 2—cold AIHA, 4—PRCA). After the induction 34 patients (74%) have achieved complete response, 10 (21.7%) partial response. Median time to hemoglobin normalization was 85 days. With regards to CLL response 9 (19%) patients have achieved CR, 2 (4%) patients—stabilization and 39 (78%)—PR. The median follow-up was 37.56 months. In AIHA group 2 patients had a relapse. Among 4 patients with PRCA 1 patient did not respond, and 1 patient had a relapse after CR, 2 remained in CR. The most common adverse events were neutropenia (62%), infections (72%), gastrointestinal complications (54%). In conclusion ibrutinib in combination with rituximab is an active second-line treatment option for patients with relapsed or refractory AIHA/PRCA and underlying CLL.

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Fig. 1: CONSORT flow diagram of the study participants.
Fig. 2: Hemoglobin and DAT response in patients with AIHA within first 2 years.
Fig. 3: Hemoglobin and DAT changes over time in patients with AIHA.
Fig. 4

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Data availability

The anonymized data collected are available as open data via open-source research platform: https://www.synapse.org/israel.

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Acknowledgements

The study was funded by Janssen (Russia). The study was funded by Janssen who also provided study drug and had the option to comment on presentation. The investigators are independent data owners with final decision for content reporting in the article and unrestricted publication rights.

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Authors and Affiliations

  1. State Budgetary Healthcare Institution of the city of Moscow City Clinical Hospital named after S.P. Botkin of Moscow City Healthcare Department, Moscow, Russian Federation

    Eugene Nikitin, Maria Kislova, Maria Shirokova, Elena Dmitrieva, Kamil Kaplanov & Vadim Ptushkin

  2. Federal State Budgetary Educational Institution of Further Professional Education “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation

    Eugene Nikitin, Irina Poddubnaya & Vadim Ptushkin

  3. State Budgetary Health Institution of the Nizhny Novgorod Region “Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko”, Nizhny, Novgorod, Russian Federation

    Dmitry Morozov, Anna Suvorova, Polina Makarovskaya & Olga Samoilova

  4. State Budgetary Healthcare Institution of the city of Moscow Blood Center named after O.K. Gavrilov of the Moscow City Healthcare Department, Moscow, Russian Federation

    Vera Belyakova & Olga Mayorova

  5. State Autonomous Healthcare Institution of the Sverdlovsk Region “Sverdlovsk Regional Clinical Hospital N 1”, Ekaterinburg, Russian Federation

    Julia Sveshnikova & Tatyana Konstantinova

  6. State Budgetary Health Institution “Volgograd Regional Clinical Oncology Center”, Volgograd, Russian Federation

    Galina Vyscub, Irina Matveeva, Anna Shipaeva & Tatyana Klitochenko

  7. National Medical Research Center for Hematology, Moscow, Russian Federation

    Bella Biderman, Andrei Sudarikov & Tatyana Obukhova

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  1. Eugene Nikitin
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Contributions

EN: Conceptualization, methodology, validation, formal analysis, investigation, resources, data curation, writing (original draft, review, and editing), visualization, supervision, project administration, funding acquisition; MK: Conceptualization, methodology, validation, formal analysis, data curation, writing (original draft, review, and editing), visualization; VB, BB, AS, TO: Investigation, writing (review and editing); DM, AS, JS, GV, IM, MS, AS, TK, PM, ED, OS, KK, TK: Investigation, resources, writing (review and editing); OM, IP, VP: Conceptualization, writing (review and editing), funding acquisition.

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Correspondence to Eugene Nikitin.

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EN reports research funding from Janssen during the conduct of the study. Other authors declare no competing interests.

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Nikitin, E., Kislova, M., Morozov, D. et al. Ibrutinib in combination with rituximab is highly effective in treatment of chronic lymphocytic leukemia patients with steroid refractory and relapsed autoimmune cytopenias. Leukemia 37, 1464–1473 (2023). https://doi.org/10.1038/s41375-023-01891-3

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