Retreatment with brentuximab vedotin in patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large-cell lymphoma: a multicenter retrospective study

Fukuhara, Noriko; Yamamoto, Go; Tsujimura, Hideki; Chou, Takaaki; Shibayama, Hirohiko; Yanai, Tomoko; Shibuya, Kazunori; Izutsu, Koji

doi:10.1080/10428194.2019.1654100

Cited by 18 publications

(21 citation statements)

References 14 publications

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“…Our study demonstrates that the Nivo + BV therapy is a potentially effective approach in this heavily pretreated patients population with 57% overall and 24% complete response rate. While BV retreatment, consistent with published data, was beneficial in patients with r/r cHL who had previously responded to BV therapy [42], only 3 out of 10 patients in current population had objective response to BV monotherapy previously. Considering that only 6 (29%) patients responded to Nivo monotherapy the results of the study may demonstrate the possible synergism of immunotherapy and targeted therapy with BV.…”

Section: Discussionsupporting

confidence: 85%

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: Discussionsupporting

confidence: 85%

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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“…We were encouraged by the high ORR and CR rate in such a heavily pretreated population, especially as the great majority of patients were previously refractory to brentuximab vedotin. Retreatment with brentuximab vedotin monotherapy in patients who previously responded to brentuximab vedotin and discontinued while in response is associated with a response rate of 53% to 60% (14,15). One study evaluated an intensified dosing schedule of brentuximab vedotin monotherapy in a small cohort of patients who were refractory to brentuximab vedotin using criteria similar to ours.…”

Section: Discussionmentioning

confidence: 95%

Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma

Chen

Herrera

Hou

et al. 2020

Clinical Cancer Research

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Purpose: In classical Hodgkin lymphoma, the malignant Reed-Sternberg cells express the cell surface marker CD30. Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers a potent cytotoxic agent, monomethyl auristatin E (MMAE), to CD30-positive cells. Although brentuximab vedotin elicits a high response rate (75%) in relapsed/refractory Hodgkin lymphoma, most patients who respond to brentuximab vedotin eventually develop resistance.Patients and Methods: We developed two brentuximab vedotin-resistant Hodgkin lymphoma cell line models using a pulsatile approach and observed that resistance to brentuximab vedotin is associated with an upregulation of multidrug resistance-1 (MDR1). We then conducted a phase I trial combining brentuximab vedotin and cyclosporine A (CsA) in patients with relapsed/refractory Hodgkin lymphoma.Results: Here, we show that competitive inhibition of MDR1 restored sensitivity to brentuximab vedotin in our brentuximab vedotin-resistant cell lines by increasing intracellular MMAE levels, and potentiated brentuximab vedotin activity in brentuximab vedotin-resistant Hodgkin lymphoma tumors in a human xenograft mouse model. In our phase I trial, the combination of brentuximab vedotin and CsA was tolerable and produced an overall and complete response rate of 75% and 42% in a population of patients who were nearly all refractory to brentuximab vedotin.Conclusions: This study may provide a new therapeutic strategy to combat brentuximab vedotin resistance in Hodgkin lymphoma. This is the first study reporting an effect of multidrug resistance modulation on the therapeutic activity of an ADC in humans. The expansion phase of the trial is ongoing and enrolling patients who are refractory to brentuximab vedotin to confirm clinical activity in this population with unmet need.

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“…Introduction of BV into the first-line setting will make the application of previous evidence of BV for relapsed/ refractory cHL difficult. However, as increasing data support the efficacy of BV re-treatment, 113,114 patients who initially respond to BV and subsequently experience relapse may be considered for BV-containing treatment strategy.…”

Section: Discussionmentioning

confidence: 99%

<p>Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma</p>

Makita

Maruyama

Tobinai

2020

OTT

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Classical Hodgkin lymphoma (cHL) is a B-cell-derived lymphoid malignancy with the most favorable prognosis among various adult malignancies. However, once it becomes refractory disease to chemotherapy or relapses after high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT), it is difficult to manage with conventional cytotoxic chemotherapy. The introduction of brentuximab vedotin (BV) has changed the treatment landscape of cHL in the past decade. Several studies demonstrated high efficacy of BV monotherapy in heavily treated patients with cHL relapsed or refractory after HDC/ASCT. Recent studies also reported high efficacy of concurrent or sequential combination of BV and chemotherapy in patients with transplant-eligible relapsed/refractory cHL at the second-line setting. In addition, a randomized phase III trial ECHELON-1 reported a positive result of BV in combination with AVD (doxorubicin, vinblastine, and dacarbazine) in patients with newly diagnosed advanced-stage cHL. In this review, we summarize available data of BV for cHL and discuss the current and future role of BV in the management of cHL.

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Retreatment with brentuximab vedotin in patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large-cell lymphoma: a multicenter retrospective study

Cited by 18 publications

References 14 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

Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma

<p>Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma</p>

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