anti-CD30 Antibody Brentuximab Vedotin Research Articles

Older patients with Hodgkin Lymphoma: Walking the tightrope of efficacy and toxicity.

Since its initial description, classical Hodgkin lymphoma (cHL) portends a greatly improved prognosis and the goal of treatment in most patients is cure with minimisation of toxicity from treatment. Outcomes in older patients (>60 years old) lag behind those of their younger counterparts however, and cure remains achievable mostly for those who can tolerate full doses of conventional chemotherapy. This review addresses the difference in biology between younger and older patients with cHL and examines the impact of frailty and comorbidities on outcomes. The toxicities of conventional chemotherapy in anthracycline-fit and -unfit patients are examined, with a particular focus on pulmonary toxicity associated with bleomycin in older patients. New advances are discussed, including the possibility of using more targeted therapies such as the anti-CD30 antibody brentuximab vedotin (BV) and checkpoint inhibitors as a method of reducing dependency on conventional chemotherapy for those less well able to tolerate it. Treatment of older patients with cHL remains an area of unmet need in hematological research, and efforts to rectify this knowledge gap should continue.

HL-024: Case Report: Re-Challenging with Pembrolizumab for a Case of Hodgkin Lymphoma with no Transplant with Multiple Relapses

In classical Hodgkin lymphoma (cHl), characterized by the overexpression of PDL1 and PDL2, there is a benefit from novel therapeutic strategy for the relapsed refractory disease, and has been approved by the FDA. A 44-year-old female patient presented in 2007 with diffuse enlarged lymph nodes. Biopsy showed a classical nodular sclerosis HL; stage IV according to the Ann Arbor classification system. She received 6 cycles of chemotherapy ABVD regimen (doxorubicin 25 mg/m2, bleomycin 10 IU/m2, vinblastine 6 mg/m2 IV, dacarbazine 375 mg/m2), leading to complete remission. Upon follow-up, end of 2008, PET-CT showed a relapse. Three cycles of chemotherapy ICE protocol were administered (cisplatin 20 mg/m2 day 1-3, etoposide 75 mg/m2 day 1-3, ifosfamide 1200 mg/m2 day 1-3, mesna 1600 mg/m2 day 1-3). PET-CT showed a complete remission, but the patient refused to have an autologous transplant due to financial difficulties. Early 2017, PET-CT showed a recurrence of disease. Treatment with the anti-CD30 antibody brentuximab vedotin 1.8 mg/kg with bendamustine 100 mg/m2 q3 weeks given for 3 cycles resulted in partial response. We continued the treatment for 3 more cycles with a complete remission. An autologous HSCT was not performed, and she continued the follow up for 1 year. December 2017 a Pet CT scan showed a new relapse, initiation of pembrolizumab 200 mg q3 weeks for 1 year with a partial response on Pet-Ct. November 2018 for financial issues, pembrolizumab was stopped (treatment not approved). A new PET-CT in April 2019 showed a progression of supra and infra diaphragmatic LNs and bone marrow disease. Re-challenging strategy, the patient was re-treated with pembrolizumab 200 mg Q3W, with evidence of disease progression in October 2019, suggesting a pseudo progression. A new PET-CT in January 2020 showed a persistent stable disease. Treatment was continued and new PET-CT in April 2020 showed a stable partial response. In summary, re-treatment with pembrolizumab is still active for non-transplanted recurrent HL with multiple previous relapses treated with pembrolizumab.

Recent treatment advances in Hodgkin lymphoma: a concise review.

The majority of patients with Hodgkin lymphoma enjoy durable remissions following front-line treatment. This typically involves combination chemotherapy with or without radiotherapy. A significant minority of patients experience relapsed/refractory disease, of whom only approximately half can be 'salvaged' with conventional second-line treatments. Until recently, for those patients either failing or who are not fit for salvage, there have been few curative alternatives. Furthermore, there is a significant risk of delayed treatment complications to conventional therapies, including secondary malignancies and cardiac disease. However, novel targeted therapies are producing excellent results in clinical trials. They provide additional treatment options for those with relapsing/refractory disease; they may have potential in front-line therapy. The anti-CD30 antibody brentuximab vedotin (BV) has been tested as monotherapy and in combination in a variety of clinical settings, including in relapsed/refractory patients and as consolidative therapy following standard second-line therapy. Nivolumab and pembrolizumab, currently used in other malignancies that are known to utilise the programmed death pathway for survival, have shown outstanding results when used as single agents in heavily pre-treated (including BV refractory) patients. Individualising and adapting a patient's treatment course, whether augmenting or rationalising therapy, based on an interim positron emission tomography/computed tomography response is an important strategy currently under exploration to minimise toxicity while maximising response. Further work is needed to explore clinical and biological factors associated with improved outcomes. Knowledge of these factors combined with the movement of novel therapies into the front-line setting will enable individualised therapy to enhance clinical responses and minimise toxicities.