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Autologous Stem Cell Transplantation in Hodgkin Lymphoma-Latest Advances in the Era of Novel Therapies.

ABSTRACT: Standard treatment for relapsed and/or refractory (r/r) Hodgkin lymphoma (HL) consists of salvage therapy, historically consisting of multiagent cytotoxic chemotherapy, followed by autologous stem cell transplantation (autoHCT) in responding patients. With this approach, most patients can proceed to autoHCT, of whom approximately half are cured. However, the introduction of the novel agents brentuximab vedotin (BV) and the checkpoint inhibitors (CPI) nivolumab and pembrolizumab has changed the decision making and peri-transplant decision making, as early incorporation of one or more of these agents can reduce or even eliminate the need for cytotoxic chemotherapy prior to autoHCT. Furthermore, post-autoHCT maintenance therapy with BV has also been shown to decrease relapse in high-risk rel/ref HL patients. In this review, we survey the current data regarding autoHCT in HL with a focus on pre-autoHCT salvage as well as maintenance strategies, and we also talk about the emerging data challenging the long-held dogma of chemosensitivity being a requirement for successful autoHCT.

SUBMITTER: Samara Y

PROVIDER: S-EPMC8996995 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Autologous Stem Cell Transplantation in Hodgkin Lymphoma-Latest Advances in the Era of Novel Therapies.

Samara Yazeed Y Mei Matthew M

Cancers 20220329 7

Standard treatment for relapsed and/or refractory (<i>r</i>/<i>r</i>) Hodgkin lymphoma (HL) consists of salvage therapy, historically consisting of multiagent cytotoxic chemotherapy, followed by autologous stem cell transplantation (autoHCT) in responding patients. With this approach, most patients can proceed to autoHCT, of whom approximately half are cured. However, the introduction of the novel agents brentuximab vedotin (BV) and the checkpoint inhibitors (CPI) nivolumab and pembrolizumab has ...[more]

PMID: 35406509

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Project description:BackgroundWe previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized.Patients and methodsPatients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV.ResultsOf the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%.ConclusionsSecond-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Project description:ImportanceMaintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma.ObservationsThe RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naïve high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naïve FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice.Conclusions and relevanceIn the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.

Dataset Information

Autologous Stem Cell Transplantation in Hodgkin Lymphoma-Latest Advances in the Era of Novel Therapies.

Publications

Autologous Stem Cell Transplantation in Hodgkin Lymphoma-Latest Advances in the Era of Novel Therapies.

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