Nivolumab in pediatric Hodgkin's lymphoma

Kozlov, Andrey V.; Kazantzev, Ilya V.; Iukhta, Tatyana V.; Толкунова, П. С.; Zvyagintseva, Darya A.; Геворгян, А. Г.; Malorodov, Anton V.; Lepik, Kirill V.; Zalyalov, Yury R.; Швецов, А. Н.; Botina, Anna; Baykov, Vadim; Morozova, Еlena V.; Punanov, Yury; Михайлова, Н. Б.; Zubarovskaya, Ludmila; Afanasyev, Boris

doi:10.18620/ctt-1866-8836-2019-8-4-41-48

Cited by 11 publications

(13 citation statements)

References 25 publications

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“…In this study, the LYRIC criteria were used to allow avoiding early discontinuation of therapy in patients with tumor pseudoprogression when this therapy can be effective in the future [43]. Moreover, LYRIC criteria have been prospectively analyzed earlier in real clinical practice in patients with r/r cHL [21] and similar ORR and DOR were demonstrated with studies using Lugano criteria.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma

et al. 2021

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Objectives Therapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure. Methods This study retrospectively analyzed 21 patients with r/r cHL who were treated with the combination of Nivo + BV after Nivo failure. The response was evaluated by PET-CT scan according to the LYRIC criteria. Adverse events (AEs) were assessed according to NCI CTCAE v.4.03. Results Median follow-up was 19 (9-47) months. The ORR was 57%. The median OS was not reached, 24 month OS was 80% (95% CI 50-93%). Median PFS was 12 months with 24 month PFS of 31% (95% CI 12-53%). Any grade AEs were observed in 12 patients (63%), 3-4 grade AEs in 2 patients (10%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after Nivo + BV was performed in 8 (38%) patients. The median time between Nivo + BV and allo-HSCT was 8 (5-21) months. Conclusions Combination of Nivo + BV in r/r cHL after nivolumab monotherapy failure is potentially an effective and safe approach.

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Section: Discussionmentioning

confidence: 99%

“…The next revolutionary step in the treatment of r/r cHL was the advent of immune checkpoint inhibitors [17]. PD-1 inhibitors nivolumab (Nivo) and pembrolizumab have shown previously unattainable results in the treatment of r/r cHL both in clinical trials [18,19] and real clinical practice [20,21].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma

et al. 2021

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“…Median number of therapy lines before auto-HSCT was 4 (3)(4)(5)(6)(7)(8). ICIs were used to induce remission before auto-HSCT in all patients.…”

Section: Methodsmentioning

confidence: 99%

“…ICIs is limited in children [5]. As for nivolumab (nivo), our previous data demonstrated its efficacy and relative safety in a small group of pediatric patients with HL [6].…”

Section: Introductionmentioning

confidence: 99%

Autologous hematopoietic stem cell transplantation after immune checkpoint inhibitor therapy in pediatric relapsed/refractory Hodgkin lymphoma

Kozlov,

Komarova,

Potanin

et al. 2023

CTT

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Effective treatment of relapsed/refractory Hodgkin lymphoma (r/r HL) in children is still a challenge, especially in case of failure after several therapy lines. The present study demonstrates high effectiveness of auto-HSCT in heavily pretreated children with HL after immune checkpoint inhibitor (ICIs) therapy. Overall 16 children with r/r HL received auto-HSCT after ICIs with OS and PFS of 93.8% and 73.1%, respectively (median follow-up, 1.3 years). The transplantation procedure was generally well tolerated, with only one death (6.3%) due to sepsis. Thus, auto-HSCT after ICIs is a promising option in pediatric r/r HL but longer follow-up is mandatory to draw valid conclusions.

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“…Еще совсем недавно возможности для терапии детей с Р-Р ЛХ были значительно ограничены и считалось, что если в течение года от начала второй линии не удавалось принципиально изменить течение болезни, то прогноз становился неблагоприятным [1]. Развитие иммунотерапии, бесспорно, улучшило шансы на излечение этих пациентов, но ауто-ТГСК до сих пор остается очень важным компонентом терапии [9,10]. В таблице 3 отражены основные публикации, посвя- Для оценки отдаленных результатов ВДПХТ с ауто-ТГСК у пациентов с Р-Р ЛХ в качестве основной конечной точки исследования чаще используют БСВ, чем ВБП.…”

Section: обсуждение результатов исследованияunclassified

Autologous hematopoietic stem cell transplantation in children with relapsed or refractory Hodgkin lymphoma

Kozlov

Казанцев

Morozova

et al. 2022

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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The majority of patients with Hodgkin lymphoma (HL) are cured, which represents one of the best cure rates in oncology. However, the prognosis is not as favorable in case of relapsed or refractory (RR) disease. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective way to consolidate remission in patients with RR HL. Despite the many years of experience and the availability of results of randomized trials confirming the efficacy of high-dose chemotherapy in adults, the role of auto-HSCT in children with HL has not been studied as extensively, and there are only a limited number of publications on the subject. As is the case with the majority of other pediatric tumors, RR HL is a rare entity, which is why it is so difficult to study it. Here we share the experience of the R. M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation in auto-HSCT in children and adolescents with HL. The study was approved by an Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint-Petersburg State Medical University. We included 54 patients with RR HL who had undergone auto-HSCT during the period from 2007 to 2021. Refractory disease (n = 29; 54 %) was diagnosed in case of HL progression either during first-line therapy or in the first 3 months after the completion of the treatment. Relapsed disease was diagnosed in 25 (46 %) children. Early HL relapse (< 12 months since the start of therapy) was evident in 18 (72 %) patients, while late HL relapse (≥ 12 months since the start of therapy) occurred in 7 (28 %) children. The median number of lines of therapy before auto-HSCT was 3 (1–6). The first line of treatment was chemotherapy in accordance with the GPOH-HD (n = 27; 50 %), BEACOPP (n = 19; 35 %), or other protocols (n = 8; 15 %); the second line involved the use of IEP/ABVD (n = 14; 27 %), DHAP (n = 12; 23%), ICE (n = 13; 25 %), or other combinations (n = 13; 25%); and third-line treatment consisted of DHAP (n = 9; 29 %), a combination of brentuximab vedotin and bendamustine (n = 8; 26%), immune checkpoint inhibitors (ICIs) (n = 7; 22.5 %) or other regimens (n = 7; 22.5 %). ICIs were used for remission induction prior to auto-HSCT in 14 (26 %) patients. Response was assessed using the Lugano classification. Status before transplantation: complete remission (CR) – 21 (39 %) patients, partial remission (PR) – 30 (56 %), disease stabilization – 2 (3.5 %), disease progression – 1 (1.5 %). The BEAM conditioning regimen was used in 17 (31 %) patients, and the BeEAM regimen – in 32 (59 %) patients. The 3-, 5- and 10-year overall survival (OS) was 88% (95 % confidence interval (CI) 74–95), 80% (95 % CI 62–90) and 63% (95 % CI 34–81) respectively. The 10-year progression-free survival (PFS) was 46% (95 % CI 24–65). The median follow-up was 3.3 (0.1–12.3) years. The long-term PFS in children with CR and PR was 72% (95 % CI 41–89) and 33 % (95 % CI 8–61) respectively (p = 0.067). A total of 9 (16.7 %) patients died during follow-up. The main cause of death was progressive HL (n = 6), while some patients died in the early post-transplant period due to infections (n = 3; 5.6 %). The median time to relapse or progression after auto-HSCT was 6 (1–77) months. Out of 17 (31 %) patients with relapsed or progressive HL after auto-HSCT, 9 (53 %) children are alive at a median follow-up of 2.3 (0.7–9) years. Considering that our study included patients who had been more extensively pre-treated (the median number of lines of therapy – 3) than patients in the majority of other studies (the median number of lines of therapy – 2), it can be assumed that our results are superior to historical data. The improvement of transplantation outcomes observed over time can be attributed to better supportive treatment and probably, to the use of immunotherapy. According to the Center for International Blood and Marrow Transplant Research (CIBMTR), it is crucially important that long-term survival in children with RR HL be monitored closely since it can be drastically different from results obtained during the first years of follow-up - due to late relapses and complications of the received treatment. The 10-year survival rates show that the RR HL problem is yet to be resolved. With the help of auto-HSCT, approximately half of children and adolescents with RR HL can be cured. One of the most important favorable prognostic factors in these patients is the achievement of CR before transplantation. The use of immunotherapy for remission induction before auto-HSCT is also promising.

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Nivolumab in pediatric Hodgkin's lymphoma

Cited by 11 publications

References 25 publications

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma

Efficacy and safety of nivolumab combined with brentuximab vedotin after nivolumab monotherapy failure in patients with relapsed and refractory classic Hodgkin lymphoma

Autologous hematopoietic stem cell transplantation after immune checkpoint inhibitor therapy in pediatric relapsed/refractory Hodgkin lymphoma

Autologous hematopoietic stem cell transplantation in children with relapsed or refractory Hodgkin lymphoma

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