Nivolumab for the treatment of relapsed and refractory classical Hodgkin lymphoma after ASCT and in ASCT-naïve patients

Although classical Hodgkin lymphoma (cHL) is usually curable, 20–30% of the patients experience treatment failure and most of them are typically treated with salvage chemotherapy and autologous stem cell transplantation (autoSCT). However, 45–55% of that subset further relapse or progress despite intensive treatment. At the advanced stage of the disease course, recently developed immunotherapeutic approaches have provided very promising results with prolonged remissions or disease stabilization in many patients. Brentuximab vedotin (BV) has been approved for patients with relapsed/refractory cHL (rr-cHL) who have failed autoSCT, as a consolidation after autoSCT in high-risk patients, as well as for patients who are ineligible for autoSCT or multiagent chemotherapy who have failed ≥ two treatment lines. However, except of the consolidation setting, 90–95% of the patients will progress and require further treatment. In this clinical setting, immune checkpoint inhibitors (CPIs) have produced impressive results. Both nivolumab and pembrolizumab have been approved for rr-cHL after autoSCT and BV failure, while pembrolizumab has also been licensed for transplant ineligible patients after BV failure. Other CPIs, sintilimab and tislelizumab, have been successfully tested in China, albeit in less heavily pretreated populations. Recent data suggest that the efficacy of CPIs may be augmented by hypomethylating agents, such as decitabine. As a result of their success in heavily pretreated disease, BV and CPIs are moving to earlier lines of treatment. BV was recently licensed by the FDA for the first-line treatment of stage III/IV Hodgkin lymphoma (HL) in combination with AVD (only stage IV according to the European Medicines Agency (EMA)). CPIs are currently being evaluated in combination with AVD in phase II trials of first-line treatment. The impact of BV and CPIs was also investigated in the setting of second-line salvage therapy. Finally, combinations of targeted therapies are under evaluation. Based on these exciting results, it appears reasonable to predict that an improvement in survival and a potential increase in the cure rates of cHL will soon become evident.

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“…Similar outcomes to those seen in clinical trials have been reported in real-life settings as well [131,132].…”

Section: Targeting Immune Checkpoint Pathways In Classical Hodgkinsupporting

confidence: 82%

Immunotherapy in Hodgkin Lymphoma: Present Status and Future Strategies

Vassilakopoulos

Chatzidimitriou

Asimakopoulos

et al. 2019

Cancers

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“…The potential drawbacks of LYRIC include the complexity of the rules and the relatively long interval (12 weeks) between initial and subsequent imaging assessment. There are three categories in IR, i.e., IR(1), IR(2), and IR(3), with complex definitions [ 3 , 7 ]. Even in our imaging core lab (Asan Image Metrics, ), dedicated central readers and image analysts for lymphoma response criteria had difficulty following the LYRIC guidelines.…”

Section: Discussionmentioning

confidence: 99%

“…Cancer immunotherapy using immune checkpoint inhibitors (ICIs) has dramatically changed the treatment of various malignancies, including solid tumors and lymphoma. Several ICIs have been approved that target cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) [ 1 , 2 , 3 , 4 ]. Extensive research over recent decades has revealed that pseudoprogression can occur in a subset of patients treated with ICIs.…”

Section: Introductionmentioning

confidence: 99%

Incidence of Immune-Mediated Pseudoprogression of Lymphoma Treated with Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis

Lee

Kim

Cho

et al. 2021

JCM

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We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords “lymphoma,” “immunotherapy,” and “pseudoprogression.” Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran’s Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06–0.17). There was no publication bias in Begg’s test (p = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08–0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs.

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“…Based on these observations, the IR was also considered as a best response type in the current analysis, representing BOR in 23.3% of patients, which is similar to our previous experience (20%). 9 To better correlate the efficacy of 40 mg nivolumab therapy with responses reported in clinical trials, the responses were also reassessed according to CT-based Lugano criteria (Supplementary Digital Content, Figure 3). In the present study, the overall response rate was 70%, and median PFS was 18.4 (95% CI, 16.3–20.6) months which are comparable to results observed during treatment with standard dosing regimen: 65% to 73% ORR, median PFS of 11.9 to 18.3 months in cohorts A-C of nivolumab pivotal study, and 64% ORR, 19.4 months median PFS previously reported by our group.…”

Section: Discussionmentioning

confidence: 99%