Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after autologous stem cell transplant in the current era of novel therapeutics: A retrospective analysis

Bair, Steven M.; Strelec, Lauren E.; Nagle, Sarah; Nasta, Sunita; Landsburg, Daniel J.; Mato, Anthony R.; Loren, Alison W.; Schuster, Stephen J.; Stadtmauer, Edward A.; Svoboda, Jakub

doi:10.1002/ajh.24792

Cited by 27 publications

(20 citation statements)

References 26 publications

(39 reference statements)

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“…At the time of data collection, 16 patients (31%) remained on the original PD-1 inhibitor. For those patients who remained on therapy at the data cutoff, median duration of treatment with a PD-1 inhibitor was 21 months (range, 2-34); among patients who discontinued therapy, median treatment duration was 6 months (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Nine of the 24 patients (38%) who achieved CR remained on the original PD-1 inhibitor at the data cutoff; those with CR who discontinued the PD-1 inhibitor did so because of toxicity (4, 17%), autoSCT (2, 8%), disease progression (1, 4%), or patient or physician preference (7, 29%).…”

Section: Exposure To Pd-1 Inhibitorsmentioning

confidence: 99%

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

et al. 2018

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Background Although classical Hodgkin lymphoma (cHL) is highly curable, 20%–30% of patients will not be cured with conventional treatments. The programmed death‐1 (PD‐1) inhibitors (PD‐1i) nivolumab and pembrolizumab have been Food and Drug Administration‐approved for relapsed/refractory (R/R) cHL. There is limited data on the real‐world experience with PD‐1i in cHL and it is unknown whether fewer selected patients treated with PD‐1i derive benefits similar to those observed in published trials. Materials and Methods We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD‐1i in the nontrial setting. The primary objective was to describe progression‐free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post‐PD‐1i therapies. Results The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD‐1i were 68%, 45%, and 23%, respectively. Twelve‐month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety‐six percent of patients with CR continue to respond at a median follow‐up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD‐1i demonstrated objective responses. Conclusion To our knowledge, this analysis is the first describing real‐world experience with PD‐1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD‐1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post‐PD‐1i systemic therapies appear active. These results support the effectiveness and tolerability of PD‐1i therapy in R/R cHL in a real‐world setting. Implications for Practice Two PD‐1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real‐world setting in the U.S. The present study demonstrates that patients treated in a real‐world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD‐1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD‐1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

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Section: Exposure To Pd-1 Inhibitorsmentioning

confidence: 99%

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

et al. 2018

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“…126 Although the potential effect of BV on the OS of patients who have failed autoSCT cannot be strictly estimated in the absence of randomized trials, it appears that an OS benefit has probably been achieved. 157,158 OS rates in the BV era appear better than prior to its introduction, and this persists when only the 'worst-case scenario' is taken into account. 158 Brentuximab vedotin as a bridge to autoSCT after inadequate response to salvage therapy.…”

Section: Brentuximab Vedotin As Salvage Therapy For Relapsed/refractomentioning

confidence: 99%

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies

Vassilakopoulos

Asimakopoulos

Konstantopoulos

et al. 2020

Therapeutic Advances in Hematology

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The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (rr-cHL) has improved considerably in recent years owing to the approval of highly active novel agents such as brentuximab vedotin and Programmed Death-1 (PD-1) inhibitors. Although no randomized trials have been conducted to provide formal proof, it is almost undisputable that the survival of these patients has been prolonged. As autologous stem-cell transplantation (SCT) remains the standard of care for second-line therapy of most patients with rr-cHL, optimization of second-line regimens with the use of brentuximab vedotin, or, in the future, checkpoint inhibitors, is promising to increase both the eligibility rate for transplant and the final outcome. The need for subsequent therapy, and especially allogeneic SCT, can be reduced with brentuximab vedotin consolidation for 1 year, while pembrolizumab is also being tested in this setting. Several other drug categories appear to be active in rr-cHL, but their development has been delayed by the appearance of brentuximab vedotin, nivolumab and pembrolizumab, which have dominated the field of rr-cHL treatment in the last 5 years. Combinations of active drugs in chemo-free approaches may further increase efficacy and hopefully reduce toxicity in rr-cHL, but are still under development.

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“…Fortunately, the past ten years has shown major advances in the treatment of r/r cHL with Food and Drug Administration (FDA) approval of three novel agents: BV, nivolumab, and pembrolizumab. In the relapsed setting, the use of novel agents has been associated with improved survival compared to traditional cytotoxic options with a median survival of 86 versus 17 months [ 6 ].…”

Section: Approach To R/r Chl With Relapse After Asct or Ineligiblementioning

confidence: 99%

“…Historically, the standard of care for patients with relapsed/refractory (r/r) disease is salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, with the advent of novel agents, including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab), the treatment landscape for r/r HL is rapidly changing [ 5 , 6 ]. In this review, we will focus on recent advances in therapy options for patients with r/r cHL.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

Voorhees

Beaven

2020

Cancers

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Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.

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Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after autologous stem cell transplant in the current era of novel therapeutics: A retrospective analysis

Cited by 27 publications

References 26 publications

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies

Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

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