Five year experience in ibrutinib therapy for relapsed and refractory mantle cell lymphoma in real world Russian clinical practice

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Abstract

Background. Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients’ outcomes, but relapse is inevitable. In phase II–III clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL.

Aim. To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials.

Materials and methods. The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 2–4, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity.

Results. From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG>2 – 18%, blastoid variant (or Ki67>40% or WBC>50×109/l) – 43%. The median number of previous treatment lines was 2 (1–11). The ORR was 78.4% (CRR – 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p<0.001), the median OS – 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months.

The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity – 15%, arrhythmia – 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications.

Conclusion. Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

About the authors

Vladimir I. Vorobyev

Botkin City Clinical Hospital

Author for correspondence.
Email: morela@mail.ru
ORCID iD: 0000-0002-2692-8961

канд. мед. наук, врач-гематолог, зав. отд-нием трансплантации костного мозга и гемопоэтических стволовых клеток №56

Russian Federation, Moscow

Eduard G. Gemdzhian

National Research Center for Hematology

Email: morela@mail.ru
ORCID iD: 0000-0002-8357-977X

ст. науч. сотр. лаб. биостатистики

Russian Federation, Moscow

Liudmila V. Fedorova

Pavlov First Saint Petersburg State Medical University

Email: morela@mail.ru
ORCID iD: 0000-0002-3275-219X

врач-гематолог отд. клинической онкологии НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой

Russian Federation, Saint Petersburg

Natalia B. Mikhailova

Pavlov First Saint Petersburg State Medical University

Email: morela@mail.ru
ORCID iD: 0000-0002-8153-8122

канд. мед. наук, врач-гематолог, рук. отд. клинической онкологии НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой

Russian Federation, Saint Petersburg

Ridvan K. Ilyasov

Efetov Crimean Republican Oncological Clinical Dispensary

Email: morela@mail.ru
ORCID iD: 0000-0003-0626-697X

врач-гематолог, зав. отд-нием гематологии

Russian Federation, Simferopol

Liliia P. Kaleikina

Republican Oncological Dispensary

Email: morela@mail.ru

врач-онколог

Russian Federation, Saransk

Olga S. Trubyakova

Vladimir City Clinical Hospital №5

Email: morela@mail.ru

врач-гематолог

Russian Federation, Vladimir

Kamil D. Kaplanov

Botkin City Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0001-6574-0518

канд. мед. наук, врач-гематолог, зав. отд-нием гематологии №11

Russian Federation, Moscow

Elena V. Melnichenko

Novosibirsk Hematology Center

Email: morela@mail.ru

врач-гематолог

Russian Federation, Novosibirsk

Elena V. Martynova

Krasnoyarsk Regional Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0002-7004-7432

врач-гематолог отд-ния гематологии

Russian Federation, Krasnoyarsk

Elena P. Yakovleva

Regional Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0002-8284-7832

врач-гематолог

Russian Federation, Barnaul

Olga Yu. Li

Sakhalin Regional Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0002-1237-6107

врач-гематолог, зав. отд-нием гематологии

Russian Federation, Yuzhno-Sakhalinsk

Elena V. Tarasenko

Pirogov City hospital №1

Email: morela@mail.ru
ORCID iD: 0000-0002-1356-736X

врач-гематолог

Russian Federation, Sevastopol

Elena P. Chumakova

Perm Regional Clinical Hospital

Email: morela@mail.ru

врач-гематолог, зав. отд-нием гематологии

Russian Federation, Perm

Natalia B. Bulieva

Regional Clinical Hospital of the Kaliningrad Region

Email: morela@mail.ru
ORCID iD: 0000-0002-4824-9484

врач-гематолог, зав. гематологическим отд-нием

Russian Federation, Kaliningrad

Ekaterina S. Nesterova

National Research Center for Hematology

Email: morela@mail.ru
ORCID iD: 0000-0002-6035-9547

канд. мед. наук, врач-гематолог отд-ния интенсивной высокодозной химиотерапии гемобластозов с круглосуточным и дневным стационаром

Russian Federation, Moscow

Oleg V. Margolin

National Research Center for Hematology

Email: morela@mail.ru
ORCID iD: 0000-0002-6211-5677

канд. мед. наук, врач-гематолог отд-ния интенсивной высокодозной химиотерапии гемобластозов с круглосуточным и дневным стационаром

Russian Federation, Moscow

Vera A. Zherebtsova

Botkin City Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0002-3052-269X

канд. мед. наук, врач-гематолог отд-ния трансплантации костного мозга и гемопоэтических стволовых клеток №56

Russian Federation, Moscow

Lev S. Butaev

Botkin City Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0002-1060-3804

врач-гематолог отд-ния трансплантации костного мозга и гемопоэтических стволовых клеток №56

Russian Federation, Moscow

Vadim V. Ptushkin

Botkin City Clinical Hospital

Email: morela@mail.ru
ORCID iD: 0000-0002-9368-6050

д-р мед. наук, врач-гематолог, зам. глав. врача по медицинской части (гематологии)

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Progression free survival (PFS) of patients (n=106) with relapse/refractory (R/R) mantle cell lymphoma (MCL) during monotherapy with ibrutinib (median follow-up 34.5 months).

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3. Fig. 2. Overall survival (OS) of patients (n=106) with R/R MCL during monotherapy with ibrutinib (median follow-up 34.5 months).

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4. Fig. 3. PFS of patients with R/R MCL, depending on the presence or absence of the blastoid variant, and/or Ki-67>40%, and/or white blood cells (WBC)>50×109/L.

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5. Fig. 4. OS of patients with R/R MCL, depending on the presence or absence of the blastoid variant and/or Ki-67>40% and/or WBC>50×109/L.

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6. Fig. 5. Factors of an unfavorable prognosis for PFS in patients with R/R MCL.

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7. Fig. 6. Factors of an unfavorable prognosis for OS in patients with R/R MCL.

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8. Fig. 7. OS after progression with ibrutinib therapy.

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